Abstract
The spread of metastatic cancer cell is the main cause of death worldwide. Cellular and molecular basis of the action of phytochemicals in the modulation of metastatic cancer highlights the importance of fruits and vegetables. Quercetin is a natural bioflavonoid present in fruits, vegetables, seeds, berries, and tea. The cancer-preventive activity of quercetin is well documented due to its anti-inflammatory, anti-proliferative and anti-angiogenic activities. However, poor water solubility and delivery, chemical instability, short half-life, and low-bioavailability of quercetin limit its clinical application in cancer chemoprevention. A better understanding of the molecular mechanism of controlled and regulated drug delivery is essential for the development of novel and effective therapies. To overcome the limitations of accessibility by quercetin, it can be delivered as nanoconjugated quercetin. Nanoconjugated quercetin has attracted much attention due to its controlled drug release, long retention in tumor, enhanced anticancer potential, and promising clinical application. The pharmacological effect of quercetin conjugated nanoparticles typically depends on drug carriers used such as liposomes, silver nanoparticles, silica nanoparticles, PLGA (Poly lactic-co-glycolic acid), PLA (poly(D,L-lactic acid)) nanoparticles, polymeric micelles, chitosan nanoparticles, etc.
In this review, we described various delivery systems of nanoconjugated quercetin like liposomes, silver nanoparticles, PLGA (Poly lactic-co-glycolic acid), and polymeric micelles including DOX conjugated micelles, metal conjugated micelles, nucleic acid conjugated micelles, and antibody-conjugated micelles on in vitro and in vivo tumor models; as well as validated their potential as promising onco-therapeutic agents in light of recent updates.
Keywords: Drug delivery, bioavailability, cancer therapy, nanoparticles, quercetin, PLGA.
Graphical Abstract
[1]
Senapati, S.; Mahanta, A.K.; Kumar, S.; Maiti, P. Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct. Target. Ther., 2018, 3, 7.
[2]
Maurya, A.K.; Vinayak, M. Breast cancer stem cell mediated aberrant signaling and epithelial-mesenchymal transition targets: Hope for breast cancer therapy. Int. J. Cancer Oncol., 2016, 3(3), 1-7.
[3]
Maurya, A.K.; Vinayak, M. PI-103 and Quercetin attenuate PI3K-AKT signaling pathway in T- cell lymphoma exposed to hydrogen Peroxide. PLoS One, 2016, 11(8)e0160686
[4]
Das, L.; Vinayak, M. Curcumin modulates glycolytic metabolism and inflammatory cytokines via Nrf 2 in dalton’s lymphoma ascites cells in vivo. Anticancer. Ag Med. Chem., 2018, 18(12), 1779-1791.
[5]
Vinayak, M. Molecular action of herbal antioxidants in regulation of cancer growth: Scope for novel anticancer drugs. Nutr. Cancer, 2018, 70(8), 1199-1209.
[6]
Neuhouser, M.L. Dietary flavonoids and cancer risk: Evidence from human population studies. Nutr. Cancer, 2004, 50(1), 1-7.
[7]
Tang, N.P.; Zhou, B.; Wang, B.; Yu, R.B.; Ma, J. Flavonoids intake and risk of lung cancer: A meta-analysis. Jpn. J. Clin. Oncol., 2009, 39(6), 352-359.
[8]
Cui, Y.; Morgenstern, H.; Greenland, S.; Tashkin, D.P.; Mao, J.T.; Cai, L.; Cozen, W.; Mack, T.M.; Lu, Q.Y.; Zhang, Z.F. Dietary flavonoid intake and lung cancer--a population-based case-control study. Cancer, 2008, 112(10), 2241-2248.
[9]
Forcados, G.E.; James, D.B.; Sallau, A.B.; Muhammad, A.; Mabeta, P. Oxidative stress and carcinogenesis: Potential of phytochemicals in breast cancer therapy. Nutr. Cancer, 2017, 69(3), 365-374.
[10]
Abraham, A.N.; Sharma, T.K.; Bansal, V.; Shukla, R. Phytochemicals as dynamic surface ligands to control nanoparticle-protein interactions. ACS Omega, 2018, 3(2), 2220-2229.
[11]
Maurya, A.K.; Vinayak, M. Modulation of PKC signaling and induction of apoptosis through suppression of reactive oxygen species and tumor necrosis factor receptor 1 (TNFR1): Key role of quercetin in cancer prevention. Tumour Biol., 2015, 36(11), 8913-8924.
[12]
D’Andrea, G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia, 2015, 106, 256-271.
[13]
Amanzadeh, E.; Esmaeili, A.; Rahgozar, S.; Nourbakhshnia, M. Application of quercetin in neurological disorders: From nutrition to nanomedicine. Rev. Neurosci., 2019, 30(5), 555-572.
[14]
Rauf, A.; Imran, M.; Khan, I.A.; Ur-Rehman, M.; Gilani, S.A.; Mehmood, Z.; Mubarak, M.S. Anticancer potential of quercetin: A comprehensive review. Phytother. Res., 2018, 32(11), 2109-2130.
[15]
Maurya, A.K.; Vinayak, M. Anticarcinogenic action of quercetin by downregulation of phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) via induction of p53 in hepatocellular carcinoma (HepG2) cell line. Mol. Biol. Rep., 2015, 42(9), 1419-1429.
[16]
Kumari, A.; Yadav, S.K.; Pakade, Y.B.; Kumar, V.; Singh, B.; Chaudhary, A.; Yadav, S.C. Nanoencapsulation and characterization of Albizia chinensis isolated antioxidant quercitrin on PLA nanoparticles. Colloids Surf. B Biointerfaces, 2011, 82(1), 224-232.
[17]
Maurya, A.K.; Vinayak, M. Improved synergistic anticancer efficacy of quercetin in combination with PI-103, rottlerin, and G0 6983 against MCF-7 and RAW 264.7 cells. In Vitro Cell. Dev. Biol. Anim., 2019, 55(1), 36-44.
[18]
Kleemann, R.; Verschuren, L.; Morrison, M.; Zadelaar, S.; van Erk, M.J.; Wielinga, P.Y.; Kooistra, T. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis, 2011, 218(1), 44-52.
[19]
Nabavi, S.F.; Russo, G.L.; Daglia, M.; Nabavi, S.M. Role of quercetin as an alternative for obesity treatment: You are what you eat! Food Chem., 2015, 179, 305-310.
[20]
Xu, D.; Hu, M-J.; Wang, Y-Q.; Cui, Y-L. Antioxidant activities of quercetin and its complexes for medicinal application. Molecules, 2019, 24(6), 1123.
[21]
Dueñas, M.; González-Manzano, S.; González-Paramás, A.; Santos-Buelga, C. Antioxidant evaluation of O-methylated metabolites of catechin, epicatechin and quercetin. J. Pharm. Biomed. Anal., 2010, 51(2), 443-449.
[22]
Boots, A.W.; Haenen, G.R.; Bast, A. Health effects of quercetin: From antioxidant to nutraceutical. Eur. J. Pharmacol., 2008, 585(2-3), 325-337.
[23]
Ganesan, S.; Faris, A.N.; Comstock, A.T.; Wang, Q.; Nanua, S.; Hershenson, M.B.; Sajjan, U.S. Quercetin inhibits rhinovirus replication in vitro and in vivo. Antiviral Res., 2012, 94(3), 258-271.
[24]
Sun, D.; Zhang, W.; Li, N.; Zhao, Z.; Mou, Z.; Yang, E.; Wang, W. Silver nanoparticles-quercetin conjugation to siRNA against drug-resistant Bacillus subtilis for effective gene silencing: In vitro and in vivo. Mater. Sci. Eng. C, 2016, 63, 522-534.
[25]
Rai, M.; Yadav, A.; Gade, A. Silver nanoparticles as a new generation of antimicrobials. Biotechnol. Adv., 2009, 27(1), 76-83.
[26]
Han, Q.; Wang, X.; Cai, S.; Liu, X.; Zhang, Y.; Yang, L.; Wang, C.; Yang, R. Quercetin nanoparticles with enhanced bioavailability as multifunctional agents toward amyloid induced neurotoxicity. J. Mater. Chem. B Mater. Biol. Med., 2018, 6(9), 1387-1393.
[27]
George, D.; Maheswari, P.U.; Begum, K.M.M.S. Synergic formulation of onion peel quercetin loaded chitosan-cellulose hydrogel with green zinc oxide nanoparticles towards controlled release, biocompatibility, antimicrobial and anticancer activity. Int. J. Biol. Macromol., 2019, 132, 784-794.
[28]
Alidadi, H.; Khorsandi, L.; Shirani, M. Effects of quercetin on tubular cell apoptosis and kidney damage in rats induced by titanium dioxide nanoparticles. Malays. J. Med. Sci., 2018, 25(2), 72-81.
[29]
Abdelhalim, M.A.K.; Qaid, H.A.; Al-Mohy, Y.; Al-Ayed, M.S. Effects of quercetin and arginine on the nephrotoxicity and lipid peroxidation induced by gold nanoparticles in vivo. Int. J. Nanomed, 2018, 13, 7765-7770.
[30]
Cruz Dos Santos, S.; Osti Silva, N.; Dos Santos Espinelli, J.B.J.; Germani Marinho, M.A.; Vieira Borges, Z.; Bruzamarello Caon Branco, N.; Faita, F.L.; Meira Soares, B.; Horn, A.P.; Parize, A.L.; Rodrigues de Lima, V. Molecular interactions and physico-chemical characterization of quercetin-loaded magnetoliposomes. Chem. Phys. Lipids, 2019, 218, 22-33.
[31]
Wen, P.; Hu, T.G.; Li, L.; Zong, M.H.; Wu, H. A colon-specific delivery system for quercetin with enhanced cancer prevention based on co-axial electrospinning. Food Funct., 2018, 9(11), 5999-6009.
[32]
Ma, J.J.; Yu, Y.G.; Yin, S.W.; Tang, C.H.; Yang, X.Q. Cellular uptake and intracellular antioxidant activity of Zein/Chitosan nanoparticles incorporated with Quercetin. J. Agric. Food Chem., 2018, 66(48), 12783-12793.
[33]
Harwood, M.; Danielewska-Nikiel, B.; Borzelleca, J.F.; Flamm, G.W.; Williams, G.M.; Lines, T.C. A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem. Toxicol., 2007, 45(11), 2179-2205.
[34]
Reinboth, M.; Wolffram, S.; Abraham, G.; Ungemach, F.R.; Cermak, R. Oral bioavailability of quercetin from different quercetin glycosides in dogs. Br. J. Nutr., 2010, 104(2), 198-203.
[35]
Hirpara, K.V.; Aggarwal, P.; Mukherjee, A.J.; Joshi, N.; Burman, A.C. Quercetin and its derivatives: Synthesis, pharmacological uses with special emphasis on anti-tumor properties and prodrug with enhanced bio-availability. Anticancer. Ag Med. Chem., 2009, 9(2), 138-161.
[36]
Mulholland, P.J.; Ferry, D.R.; Anderson, D.; Hussain, S.A.; Young, A.M.; Cook, J.E.; Hodgkin, E.; Seymour, L.W.; Kerr, D.J. Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin. Ann. Oncol., 2001, 12(2), 245-248.
[37]
Anand David, A.V.; Arulmoli, R.; Parasuraman, S. Overviews of biological importance of Quercetin: A bioactive flavonoid. Pharmacogn. Rev., 2016, 10(20), 84-89.
[38]
Ezzati Nazhad Dolatabadi, J.; Mokhtarzadeh, A.; Ghareghoran, S.M.; Dehghan, G. Synthesis, characterization and antioxidant property of Quercetin-Tb(III) complex. Adv. Pharm. Bull., 2014, 4(2), 101-104.
[39]
Gao, X.; Wang, B.; Wei, X.; Men, K.; Zheng, F.; Zhou, Y.; Zheng, Y.; Gou, M.; Huang, M.; Guo, G.; Huang, N.; Qian, Z.; Wei, Y. Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer. Nanoscale, 2012, 4(22), 7021-7030.
[40]
Nam, J.S.; Sharma, A.R.; Nguyen, L.T.; Chakraborty, C.; Sharma, G.; Lee, S.S. Application of bioactive quercetin in oncotherapy: From nutrition to nanomedicine. Molecules, 2016, 21(1)E108
[41]
Maurya, A.K.; Vinayak, M. Quercetin regresses Dalton’s lymphoma growth via suppression of PI3K/AKT signaling leading to upregulation of p53 and decrease in energy metabolism. Nutr. Cancer, 2015, 67(2), 354-363.
[42]
Zhu, B.; Yu, L.; Yue, Q. Co-delivery of vincristine and quercetin by nanocarriers for lymphoma combination chemotherapy. Biomed. Pharmacother., 2017, 91, 287-294.
[43]
Maurya, A.K.; Vinayak, M. PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma. Leuk. Lymphoma, 2017, 58(5), 1153-1161.
[44]
Maurya, A.K.; Vinayak, M. Quercetin attenuates cell survival, inflammation, and angiogenesis via modulation of AKT signaling in murine T-cell lymphoma. Nutr. Cancer, 2017, 69(3), 470-480.
[45]
Rivera Rivera, A.; Castillo-Pichardo, L.; Gerena, Y.; Dharmawardhane, S. Anti-breast cancer potential of Quercetin via the Akt/AMPK/mammalian Target of Rapamycin (mTOR) signaling cascade. PLoS One, 2016, 11(6)e0157251
[46]
Seo, H.S.; Ku, J.M.; Choi, H.S.; Choi, Y.K.; Woo, J.K.; Kim, M.; Kim, I.; Na, C.H.; Hur, H.; Jang, B.H.; Shin, Y.C.; Ko, S.G. Quercetin induces caspase-dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 signaling in HER2-overexpressing BT-474 breast cancer cells. Oncol. Rep., 2016, 36(1), 31-42.
[47]
Subramaniam, D.; Kaushik, G.; Dandawate, P.; Anant, S. Targeting cancer stem cells for chemoprevention of pancreatic cancer. Curr. Med. Chem., 2018, 25(22), 2585-2594.
[48]
Gavrilas, L.I.; Ionescu, C.; Tudoran, O.; Lisencu, C.; Balacescu, O.; Miere, D. The role of bioactive dietary components in modulating miRNA expression in colorectal cancer. Nutrients, 2016, 8(10)E590
[49]
Saleem, T.H.; Attya, A.M.; Ahmed, E.A.; Ragab, S.M.; Ali Abdallah, M.A.; Omar, H.M. Possible protective effects of quercetin and sodium gluconate against colon cancer induction by dimethylhydrazine in mice. Asian Pac. J. Cancer Prev., 2015, 16(14), 5823-5828.
[50]
Engen, A.; Maeda, J.; Wozniak, D.E.; Brents, C.A.; Bell, J.J.; Uesaka, M.; Aizawa, Y.; Kato, T.A. Induction of cytotoxic and genotoxic responses by natural and novel quercetin glycosides. Mutat. Res. Genet. Toxicol. Environ. Mutagen., 2015, 784-785, 15-22.
[51]
Maurya, A.K.; Vinayak, M. Abstract A07: Decline in the growth of murine T-cell lymphoma via modulation of PI3K signaling pathway: Key role of quercetin and PI-103. Mol. Cancer Ther., 2015, 14(Suppl. 7), A07-A07.
[52]
Chen, L.C.; Chen, Y.C.; Su, C.Y.; Hong, C.S.; Ho, H.O.; Sheu, M.T. Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study. Int. J. Nanomedicine, 2016, 11, 1557-1566.
[53]
Del Follo-Martinez, A.; Banerjee, N.; Li, X.; Safe, S.; Mertens-Talcott, S. Resveratrol and quercetin in combination have anticancer activity in colon cancer cells and repress oncogenic microRNA-27a. Nutr. Cancer, 2013, 65(3), 494-504.
[54]
Chan, S-T.; Chuang, C-H.; Lin, Y-C.; Liao, J-W.; Lii, C-K.; Yeh, S-L. Quercetin enhances the antitumor effect of trichostatin A and suppresses muscle wasting in tumor-bearing mice. Food Funct., 2018, 9(2), 871-879.
[55]
Serri, C.; Quagliariello, V.; Iaffaioli, R.V.; Fusco, S.; Botti, G.; Mayol, L.; Biondi, M. Combination therapy for the treatment of pancreatic cancer through hyaluronic acid-decorated nanoparticles loaded with quercetin and gemcitabine: A preliminary in vitro study. J. Cell. Physiol., 2019, 234(4), 4959-4969.
[56]
Flusberg, D.A.; Sorger, P.K. Surviving apoptosis: Life-death signaling in single cells. Trends Cell Biol., 2015, 25(8), 446-458.
[57]
Pobezinskaya, Y.L.; Liu, Z. The role of TRADD in death receptor signaling. Cell Cycle, 2012, 11(5), 871-876.
[58]
Russo, M.; Spagnuolo, C.; Bilotto, S.; Tedesco, I.; Maiani, G.; Russo, G.L.; Russo, M.; Spagnuolo, C.; Bilotto, S.; Tedesco, I.; Maiani, G.; Russo, G.L. Inhibition of protein kinase CK2 by quercetin enhances CD95-mediated apoptotis in a human thymus-derived T cell line. Food Res. Int., 2014, 63(B), 244-251.
[59]
Chou, C.C.; Yang, J.S.; Lu, H.F.; Ip, S.W.; Lo, C.; Wu, C.C.; Lin, J.P.; Tang, N.Y.; Chung, J.G.; Chou, M.J.; Teng, Y.H.; Chen, D.R. Quercetin-mediated cell cycle arrest and apoptosis involving activation of a caspase cascade through the mitochondrial pathway in human breast cancer MCF-7 cells. Arch. Pharm. Res., 2010, 33(8), 1181-1191.
[60]
Haghiac, M.; Walle, T. Quercetin induces necrosis and apoptosis in SCC-9 oral cancer cells. Nutr. Cancer, 2005, 53(2), 220-231.
[61]
Mozhgan Farzami Sepehr, S.B.J.B.H. The Cuscuta kotschyana effects on breast cancer cells line MCF7. J. Med. Plants Res., 2011, 5(27), 6344-6351.
[62]
Niu, G.; Yin, S.; Xie, S.; Li, Y.; Nie, D.; Ma, L.; Wang, X.; Wu, Y. Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells. Acta Biochim. Biophys. Sin. (Shanghai), 2011, 43(1), 30-37.
[63]
Hu, J.; Wang, J.; Wang, G.; Yao, Z.; Dang, X. Pharmacokinetics and antitumor efficacy of DSPE-PEG2000 polymeric liposomes loaded with quercetin and temozolomide: Analysis of their effectiveness in enhancing the chemosensitization of drug-resistant glioma cells. Int. J. Mol. Med., 2016, 37(3), 690-702.
[64]
Hu, J.; Yu, Q.; Zhao, F.; Ji, J.; Jiang, Z.; Chen, X.; Gao, P.; Ren, Y.; Shao, S.; Zhang, L.; Yan, M. Protection of quercetin against triptolide-induced apoptosis by suppressing oxidative stress in rat Leydig cells. Chem. Biol. Interact., 2015, 240, 38-46.
[65]
Shen, S.C.; Lee, W.R.; Yang, L.Y.; Tsai, H.H.; Yang, L.L.; Chen, Y.C. Quercetin enhancement of arsenic-induced apoptosis via stimulating ROS-dependent p53 protein ubiquitination in human HaCaT keratinocytes. Exp. Dermatol., 2012, 21(5), 370-375.
[66]
Zhang, J.Y.; Yi, T.; Liu, J.; Zhao, Z.Z.; Chen, H.B. Quercetin induces apoptosis via the mitochondrial pathway in KB and KBv200 cells. J. Agric. Food Chem., 2013, 61(9), 2188-2195.
[67]
Zhang, Q.; Zhao, X.H.; Wang, Z.J. Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol. In Vitro, 2009, 23(5), 797-807.
[68]
Choi, J.A.; Kim, J.Y.; Lee, J.Y.; Kang, C.M.; Kwon, H.J.; Yoo, Y.D.; Kim, T.W.; Lee, Y.S.; Lee, S.J. Induction of cell cycle arrest and apoptosis in human breast cancer cells by quercetin. Int. J. Oncol., 2001, 19(4), 837-844.
[69]
Lee, Y.K.; Hwang, J.T.; Kwon, D.Y.; Surh, Y.J.; Park, O.J. Induction of apoptosis by quercetin is mediated through AMPKalpha1/ASK1/p38 pathway. Cancer Lett., 2010, 292(2), 228-236.
[70]
Kim, M.C.; Lee, H.J.; Lim, B.; Ha, K.T.; Kim, S.Y.; So, I.; Kim, B.J. Quercetin induces apoptosis by inhibiting MAPKs and TRPM7 channels in AGS cells. Int. J. Mol. Med., 2014, 33(6), 1657-1663.
[71]
Lee, K.H.; Yoo, C.G. Simultaneous inactivation of GSK-3β suppresses quercetin-induced apoptosis by inhibiting the JNK pathway. Am. J. Physiol. Lung Cell. Mol. Physiol., 2013, 304(11), L782-L789.
[72]
Vidya Priyadarsini, R.; Senthil Murugan, R.; Maitreyi, S.; Ramalingam, K.; Karunagaran, D.; Nagini, S. The flavonoid quercetin induces cell cycle arrest and mitochondria-mediated apoptosis in human cervical cancer (HeLa) cells through p53 induction and NF-κB inhibition. Eur. J. Pharmacol., 2010, 649(1-3), 84-91.
[73]
Chen, X.; Dong, X.S.; Gao, H.Y.; Jiang, Y.F.; Jin, Y.L.; Chang, Y.Y.; Chen, L.Y.; Wang, J.H. Suppression of HSP27 increases the antitumor effects of quercetin in human leukemia U937 cells. Mol. Med. Rep., 2016, 13(1), 689-696.
[74]
Mukherjee, A.; Khuda-Bukhsh, A.R. Quercetin down-regulates IL-6/STAT-3 signals to induce mitochondrial-mediated apoptosis in a nonsmall- cell lung-cancer cell line, A549. J. Pharmacopuncture, 2015, 18(1), 19-26.
[75]
Ranganathan, S.; Halagowder, D.; Sivasithambaram, N.D. Quercetin suppresses twist to induce apoptosis in MCF-7 breast cancer cells. PLoS One, 2015, 10(10)e0141370
[76]
Ward, A.B.; Mir, H.; Kapur, N.; Gales, D.N.; Carriere, P.P.; Singh, S. Quercetin inhibits prostate cancer by attenuating cell survival and inhibiting anti-apoptotic pathways. World J. Surg. Oncol., 2018, 16(1), 108.
[77]
Granado-Serrano, A.B.; Martín, M.A.; Bravo, L.; Goya, L.; Ramos, S. Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J. Nutr., 2006, 136(11), 2715-2721.
[78]
Walker, E.H.; Pacold, M.E.; Perisic, O.; Stephens, L.; Hawkins, P.T.; Wymann, M.P.; Williams, R.L. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol. Cell, 2000, 6(4), 909-919.
[79]
Datta, S.R.; Dudek, H.; Tao, X.; Masters, S.; Fu, H.; Gotoh, Y.; Greenberg, M.E. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 1997, 91(2), 231-241.
[80]
Pap, M.; Cooper, G.M. Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J. Biol. Chem., 1998, 273(32), 19929-19932.
[81]
Dickey, A.; Schleicher, S.; Leahy, K.; Hu, R.; Hallahan, D.; Thotala, D.K. GSK-3β inhibition promotes cell death, apoptosis, and in vivo tumor growth delay in neuroblastoma Neuro-2A cell line. J. Neurooncol., 2011, 104(1), 145-153.
[82]
Chiang, G.G.; Abraham, R.T. Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase. J. Biol. Chem., 2005, 280(27), 25485-25490.
[83]
Hung, C.M.; Garcia-Haro, L.; Sparks, C.A.; Guertin, D.A. mTOR-dependent cell survival mechanisms. Cold Spring Harb. Perspect. Biol., 2012, 4(12)a008771
[84]
Simpson, D.R.; Mell, L.K.; Cohen, E.E. Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck. Oral Oncol., 2015, 51(4), 291-298.
[85]
Mabuchi, S.; Kuroda, H.; Takahashi, R.; Sasano, T. The PI3K/AKT/mTOR pathway as a therapeutic target in ovarian cancer. Gynecol. Oncol., 2015, 137(1), 173-179.
[86]
Martelli, A.M.; Evangelisti, C.; Chiarini, F.; Grimaldi, C.; Cappellini, A.; Ognibene, A.; McCubrey, J.A. The emerging role of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in normal myelopoiesis and leukemogenesis. Biochim. Biophys. Acta, 2010, 1803(9), 991-1002.
[87]
Bai, D.; Ueno, L.; Vogt, P.K. Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt. Int. J. Cancer, 2009, 125(12), 2863-2870.
[88]
Choi, K.C.; Chung, W.T.; Kwon, J.K.; Yu, J.Y.; Jang, Y.S.; Park, S.M.; Lee, S.Y.; Lee, J.C. Inhibitory effects of quercetin on aflatoxin B1-induced hepatic damage in mice. Food Chem. Toxicol., 2010, 48(10), 2747-2753.
[89]
Ventura, A.; Kirsch, D.G.; McLaughlin, M.E.; Tuveson, D.A.; Grimm, J.; Lintault, L.; Newman, J.; Reczek, E.E.; Weissleder, R.; Jacks, T. Restoration of p53 function leads to tumour regression in vivo. Nature, 2007, 445(7128), 661-665.
[91]
Mayo, L.D.; Donner, D.B. The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network. Trends Biochem. Sci., 2002, 27(9), 462-467.
[92]
Zhao, P.; Mao, J.M.; Zhang, S.Y.; Zhou, Z.Q.; Tan, Y.; Zhang, Y. Quercetin induces HepG2 cell apoptosis by inhibiting fatty acid biosynthesis. Oncol. Lett., 2014, 8(2), 765-769.
[93]
Jia, L.; Huang, S.; Yin, X.; Zan, Y.; Guo, Y.; Han, L. Quercetin suppresses the mobility of breast cancer by suppressing glycolysis through Akt-mTOR pathway mediated autophagy induction. Life Sci., 2018, 208, 123-130.
[94]
Adams, R.H.; Alitalo, K. Molecular regulation of angiogenesis and lymphangiogenesis. Nat. Rev. Mol. Cell Biol., 2007, 8(6), 464-478.
[95]
Graupera, M.; Potente, M. Regulation of angiogenesis by PI3K signaling networks. Exp. Cell Res., 2013, 319(9), 1348-1355.
[96]
Ma, F.; Zhang, L.; Westlund, K.N. Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons. Mol. Pain, 2009, 5, 31.
[97]
Fang, J.; Ding, M.; Yang, L.; Liu, L.Z.; Jiang, B.H. PI3K/PTEN/AKT signaling regulates prostate tumor angiogenesis. Cell. Signal., 2007, 19(12), 2487-2497.
[98]
Sobolewski, C.; Cerella, C.; Dicato, M.; Ghibelli, L.; Diederich, M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int. J. Cell Biol., 2010, 2010215158
[99]
Das, L.; Vinayak, M. Long term effect of curcumin in restoration of tumour suppressor p53 and phase-II antioxidant enzymes via activation of Nrf2 signalling and modulation of inflammation in prevention of cancer. PLoS One, 2015, 10(4)e0124000
[100]
Subbaramaiah, K.; Altorki, N.; Chung, W.J.; Mestre, J.R.; Sampat, A.; Dannenberg, A.J. Inhibition of cyclooxygenase-2 gene expression by p53. J. Biol. Chem., 1999, 274(16), 10911-10915.
[101]
Jeon, J-S.; Kwon, S.; Ban, K.; Kwon Hong, Y.; Ahn, C.; Sung, J-S.; Choi, I. Regulation of the intracellular ROS level is critical for the antiproliferative effect of Quercetin in the hepatocellular carcinoma cell line HepG2. Nutr. Cancer, 2019, 71(5), 861-869.
[102]
Jadhav, N.R.; Nadaf, S.J.; Lohar, D.A.; Ghagare, P.S.; Powar, T.A. Phytochemicals formulated as nanoparticles: Inventions, recent patents and future prospects. Recent Pat. Drug Deliv. Formul., 2017, 11(3), 173-186.
[103]
Manach, C.; Scalbert, A.; Morand, C.; Rémésy, C.; Jiménez, L. Polyphenols: food sources and bioavailability. Am. J. Clin. Nutr., 2004, 79(5), 727-747.
[104]
Weldin, J.; Jack, R.; Dugaw, K.; Kapur, R.P. Quercetin, an over-the-counter supplement, causes neuroblastoma-like elevation of plasma homovanillic acid. Pediatr. Dev. Pathol., 2003, 6(6), 547-551.
[105]
Konishi, Y.; Zhao, Z.; Shimizu, M. Phenolic acids are absorbed from the rat stomach with different absorption rates. J. Agric. Food Chem., 2006, 54(20), 7539-7543.
[106]
Németh, K.; Plumb, G.W.; Berrin, J.G.; Juge, N.; Jacob, R.; Naim, H.Y.; Williamson, G.; Swallow, D.M.; Kroon, P.A. Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans. Eur. J. Nutr., 2003, 42(1), 29-42.
[107]
Murota, K.; Terao, J. Quercetin appears in the lymph of unanesthetized rats as its phase II metabolites after administered into the stomach. FEBS Lett., 2005, 579(24), 5343-5346.
[108]
Spencer, J.P.; Kuhnle, G.G.; Williams, R.J.; Rice-Evans, C. Intracellular metabolism and bioactivity of quercetin and its in vivo metabolites. Biochem. J., 2003, 372(Pt 1), 173-181.
[109]
de Boer, V.C.; Dihal, A.A.; van der Woude, H.; Arts, I.C.; Wolffram, S.; Alink, G.M.; Rietjens, I.M.; Keijer, J.; Hollman, P.C. Tissue distribution of quercetin in rats and pigs. J. Nutr., 2005, 135(7), 1718-1725.
[110]
Lee, J.; Mitchell, A.E. Pharmacokinetics of quercetin absorption from apples and onions in healthy humans. J. Agric. Food Chem., 2012, 60(15), 3874-3881.
[111]
Kaşıkcı, M.B.; Bağdatlıoğlu, N. Bioavailability of Quercetin. Curr. Res. Nutr. Food Sci., 2016, 4, 146-151.
[112]
Tran, T.H.; Guo, Y.; Song, D.; Bruno, R.S.; Lu, X. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. J. Pharm. Sci., 2014, 103(3), 840-852.
[113]
Dian, L.; Yu, E.; Chen, X.; Wen, X.; Zhang, Z.; Qin, L.; Wang, Q.; Li, G.; Wu, C. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles. Nanoscale Res. Lett., 2014, 9(1), 2406.
[114]
Xu, G.; Shi, H.; Ren, L.; Gou, H.; Gong, D.; Gao, X.; Huang, N. Enhancing the anti-colon cancer activity of quercetin by self-assembled micelles. Int. J. Nanomed, 2015, 10, 2051-2063.
[115]
Matsumura, Y.; Kataoka, K. Preclinical and clinical studies of anticancer agent-incorporating polymer micelles. Cancer Sci., 2009, 100(4), 572-579.
[116]
Guo, Y.; Bruno, R.S. Endogenous and exogenous mediators of quercetin bioavailability. J. Nutr. Biochem., 2015, 26(3), 201-210.
[117]
Almeida, A.F.; Borge, G.I.A.; Piskula, M.; Tudose, A.; Tudoreanu, L.; Valentová, K.; Williamson, G.; Santos, C.N. Bioavailability of Quercetin in humans with a focus on interindividual variation. Compr. Rev. Food Sci. Food Saf., 2018, 17, 714-731.
[118]
Mu, Y.; Fu, Y.; Li, J.; Yu, X.; Li, Y.; Wang, Y.; Wu, X.; Zhang, K.; Kong, M.; Feng, C.; Chen, X. Multifunctional quercetin conjugated chitosan nano-micelles with P-gp inhibition and permeation enhancement of anticancer drug. Carbohydr. Polym., 2019, 203, 10-18.
[119]
Ahmad, N.; Ahmad, R.; Naqvi, A.A.; Alam, M.A.; Abdur Rub, R.; Ahmad, F.J. Enhancement of Quercetin oral bioavailability by self-nanoemulsifying drug delivery system and their quantification through ultra high performance liquid chromatography and mass spectrometry in cerebral ischemia. Drug Res. (Stuttg.), 2017, 67(10), 564-575.
[120]
Rezaei-Sadabady, R.; Eidi, A.; Zarghami, N.; Barzegar, A. Intracellular ROS protection efficiency and free radical-scavenging activity of quercetin and quercetin-encapsulated liposomes. Artif. Cells Nanomed. Biotechnol., 2016, 44(1), 128-134.
[121]
Lockhart, J.N.; Stevens, D.M.; Beezer, D.B.; Kravitz, A.; Harth, E. Dual drug delivery of tamoxifen and quercetin: Regulated metabolism for anticancer treatment with nanosponges. J. Control Release., 2015, 220(Pt B), 751-757.
[122]
des Rieux, A.; Fievez, V.; Garinot, M.; Schneider, Y.J.; Préat, V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J. Control. Release, 2006, 116(1), 1-27.
[123]
McClements, D.J.; Decker, E.A.; Park, Y.; Weiss, J. Structural design principles for delivery of bioactive components in nutraceuticals and functional foods. Crit. Rev. Food Sci. Nutr., 2009, 49(6), 577-606.
[124]
Rodriguez-Nogales, C.; Noguera, R.; Patrick, C.; Blanco-Prieto, M.J.J. Therapeutic opportunities in neuroblastoma using nanotechnology. J. Pharmacol. Exper. Ther., 2019. jpet.118.255067.
[125]
Caddeo, C.; Díez-Sales, O.; Pons, R.; Carbone, C.; Ennas, G.; Puglisi, G.; Fadda, A.M.; Manconi, M. Cross-linked chitosan/liposome hybrid system for the intestinal delivery of quercetin. J. Colloid Interface Sci., 2016, 461, 69-78.
[126]
Rahimi, S.; Khoee, S.; Ghandi, M. Preparation and characterization of rod-like chitosan-quinoline nanoparticles as pH-responsive nanocarriers for quercetin delivery. Int. J. Biol. Macromol., 2019, 128, 279-289.
[127]
Barbosa, A.I.; Costa Lima, S.A.; Reis, S. Application of pH-responsive fucoidan/chitosan nanoparticles to improve oral quercetin delivery. Molecules, 2019, 24(2), 346.
[128]
Priprem, S.S.; Na, H-K.; Surh, Y-J.; Chulasiri, M. Effect of formulations of nanosized Quercetin liposomes on COX-2 and NF-kB in MCF-10A Cells. Pharm. Nanotechnol., 2013, 1(1), 26-34.
[129]
Priprem, A.; Watanatorn, J.; Sutthiparinyanont, S.; Phachonpai, W.; Muchimapura, S. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomedicine (Lond.), 2008, 4(1), 70-78.
[130]
Ren, J.; Fang, Z.; Jiang, L.; Du, Q. Quercetin-containing self-assemble proliposome preparation and evaluation. J. Liposome Res., 2017, 27(4), 335-342.
[131]
Zheng, N.G.; Mo, S.J.; Li, J.P.; Wu, J.L. Anti-CSC effects in human esophageal squamous cell carcinomas and Eca109/9706 cells induced by nanoliposomal quercetin alone or combined with CD 133 antiserum. Asian Pac. J. Cancer Prev., 2014, 15(20), 8679-8684.
[132]
Martirosyan, A.; Grintzalis, K.; Polet, M.; Laloux, L.; Schneider, Y.J. Tuning the inflammatory response to silver nanoparticles via quercetin in Caco-2 (co-)cultures as model of the human intestinal mucosa. Toxicol. Lett., 2016, 253, 36-45.
[133]
Mittal, A.K.; Kumar, S.; Banerjee, U.C. Quercetin and gallic acid mediated synthesis of bimetallic (silver and selenium) nanoparticles and their antitumor and antimicrobial potential. J. Colloid Interface Sci., 2014, 431, 194-199.
[134]
Pandey, S.K.; Patel, D.K.; Maurya, A.K.; Thakur, R.; Mishra, D.P.; Vinayak, M.; Haldar, C.; Maiti, P. Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles. Int. J. Biol. Macromol., 2016, 89, 99-110.
[135]
Suksiriworapong, J.; Sripha, K.; Kreuter, J.; Junyaprasert, V.B. Functionalized (poly(ɛ-caprolactone))2-poly(ethylene glycol) nanoparticles with grafting nicotinic acid as drug carriers. Int. J. Pharm., 2012, 423(2), 562-570.
[136]
Suksiriworapong, J.; Phoca, K.; Ngamsom, S.; Sripha, K.; Moongkarndi, P.; Junyaprasert, V.B. Comparison of poly(ε-caprolactone) chain lengths of poly(ε-caprolactone)-co-d-α-tocopheryl-poly(ethylene glycol) 1000 succinate nanoparticles for enhancement of quercetin delivery to SKBR3 breast cancer cells. Eur. J. Pharm. Biopharm., 2016, 101, 15-24.
[137]
Gupta, A.; Kaur, C.D.; Saraf, S.; Saraf, S. Formulation, characterization, and evaluation of ligand-conjugated biodegradable quercetin nanoparticles for active targeting. Artif. Cells Nanomed. Biotechnol., 2016, 44(3), 960-970.
[138]
Lv, L.; Liu, C.; Chen, C.; Yu, X.; Chen, G.; Shi, Y.; Qin, F.; Ou, J.; Qiu, K.; Li, G. Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer. Oncotarget, 2016, 7(22), 32184-32199.
[139]
Guan, X.; Gao, M.; Xu, H.; Zhang, C.; Liu, H.; Lv, L.; Deng, S.; Gao, D.; Tian, Y. Quercetin-loaded poly (lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for the targeted treatment of liver cancer. Drug Deliv., 2016, 23(9), 3307-3318.
[140]
Wang, C.; Su, L.; Wu, C.; Wu, J.; Zhu, C.; Yuan, G. RGD peptide targeted lipid-coated nanoparticles for combinatorial delivery of sorafenib and quercetin against hepatocellular carcinoma. Drug Dev. Ind. Pharm., 2016, 42(12), 1938-1944.
[141]
Bishayee, K.; Khuda-Bukhsh, A.R.; Huh, S.O. PLGA-loaded gold-nanoparticles precipitated with Quercetin downregulate HDAC-Akt activities controlling proliferation and activate p53-ROS crosstalk to induce apoptosis in hepatocarcinoma cells. Mol. Cells, 2015, 38(6), 518-527.
[142]
Pimple, S.; Manjappa, A.S.; Ukawala, M.; Murthy, R.S. PLGA nanoparticles loaded with etoposide and quercetin dihydrate individually: in vitro cell line study to ensure advantage of combination therapy. Cancer Nanotechnol., 2012, 3(1-6), 25-36.
[143]
Zhao, J.; Liu, J.; Wei, T.; Ma, X.; Cheng, Q.; Huo, S.; Zhang, C.; Zhang, Y.; Duan, X.; Liang, X.J. Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo. Nanoscale, 2016, 8(9), 5126-5138.
[144]
Pang, X.; Lu, Z.; Du, H.; Yang, X.; Zhai, G. Hyaluronic acid-quercetin conjugate micelles: Synthesis, characterization, in vitro and in vivo evaluation. Colloids Surf. B Biointerfaces, 2014, 123, 778-786.
[145]
Tan, B.J.; Liu, Y.; Chang, K.L.; Lim, B.K.; Chiu, G.N. Perorally active nanomicellar formulation of quercetin in the treatment of lung cancer. Int. J. Nanomed, 2012, 7, 651-661.
[146]
Zhao, L.; Shi, Y.; Zou, S.; Sun, M.; Lil, L.; Zhail, G. Formulation and in vitro evaluation of quercetin loaded polymeric micelles composed of pluronic P123 and D-a-tocopheryl polyethylene glycol succinate. J. Biomed. Nanotechnol., 2011, 7(3), 358-365.
[147]
Khonkarn, R.; Mankhetkorn, S.; Hennink, W.E.; Okonogi, S. PEG-OCL micelles for quercetin solubilization and inhibition of cancer cell growth. Eur. J. Pharm. Biopharm., 2011, 79(2), 268-275.
[148]
Sun, C.; Ding, Y.; Zhou, L.; Shi, D.; Sun, L.; Webster, T.J.; Shen, Y. Noninvasive nanoparticle strategies for brain tumor targeting. Nanomedicine, 2017, 13(8), 2605-2621.
[149]
Lainé, A.L.; Clavreul, A.; Rousseau, A.; Tétaud, C.; Vessieres, A.; Garcion, E.; Jaouen, G.; Aubert, L.; Guilbert, M.; Benoit, J.P.; Toillon, R.A.; Passirani, C. Inhibition of ectopic glioma tumor growth by a potent ferrocenyl drug loaded into stealth lipid nanocapsules. Nanomedicine, 2014, 10(8), 1667-1677.
[150]
Jain, A.K.; Thanki, K.; Jain, S. Novel self-nanoemulsifying formulation of quercetin: Implications of pro-oxidant activity on the anticancer efficacy. Nanomedicine, 2014, 10(5), 959-969.
[151]
Ghosh, S.; Sarkar, S.; Choudhury, S.T.; Ghosh, T.; Das, N. Triphenyl phosphonium coated nano-quercetin for oral delivery: Neuroprotective effects in attenuating age related global moderate cerebral ischemia reperfusion injury in rats. Nanomedicine , 2017, 13(8), 2439-2450.
[152]
Penalva, R.; González-Navarro, C.J.; Gamazo, C.; Esparza, I.; Irache, J.M. Zein nanoparticles for oral delivery of quercetin: Pharmacokinetic studies and preventive anti-inflammatory effects in a mouse model of endotoxemia. Nanomedicine (Lond.), 2017, 13(1), 103-110.
[153]
Sedaghat Doost, A.; Kassozi, V.; Grootaert, C.; Claeys, M.; Dewettinck, K.; Van Camp, J.; Van der Meeren, P. Self-assembly, functionality, and in-vitro properties of quercetin loaded nanoparticles based on shellac-almond gum biological macromolecules. Int. J. Biol. Macromol., 2019, 129, 1024-1033.
[154]
Fang, J.; Nakamura, H.; Maeda, H. The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv. Drug Deliv. Rev., 2011, 63(3), 136-151.
[155]
Patra, A.; Satpathy, S.; Shenoy, A.K.; Bush, J.A.; Kazi, M.; Hussain, M.D. Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug resistant cancers. Int. J. Nanomedicine, 2018, 13, 2869-2881.
[156]
Men, K.; Duan, X.; Wei, X.W.; Gou, M.L.; Huang, M.J.; Chen, L.J.; Qian, Z.Y.; Wei, Y.Q. Nanoparticle-delivered quercetin for cancer therapy. Anticancer. Agents Med. Chem., 2014, 14(6), 826-832.
[157]
Sharma, G.; Park, J.; Sharma, A.R.; Jung, J.S.; Kim, H.; Chakraborty, C.; Song, D.K.; Lee, S.S.; Nam, J.S. Methoxy poly(ethylene glycol)-poly(lactide) nanoparticles encapsulating quercetin act as an effective anticancer agent by inducing apoptosis in breast cancer. Pharm. Res., 2015, 32(2), 723-735.
[158]
Ahmad, N.; Banala, V.T.; Kushwaha, P.; Karvande, A.; Sharma, S.; Tripathi, A.K.; Verma, A.; Trivedi, R.; Mishra, P.R. Quercetin-loaded solid lipid nanoparticles improve osteoprotective activity in an ovariectomized rat model: A preventive strategy for post-menopausal osteoporosis. RSC Advances, 2016, 6(100), 97613-97628.
[159]
Castangia, I.; Nácher, A.; Caddeo, C.; Merino, V.; Díez-Sales, O.; Catalán-Latorre, A.; Fernàndez-Busquets, X.; Fadda, A.M.; Manconi, M. Therapeutic efficacy of quercetin enzyme-responsive nanovesicles for the treatment of experimental colitis in rats. Acta Biomater., 2015, 13, 216-227.
[160]
Singh, S.K.; Singh, S.; Lillard, J.W., Jr; Singh, R. Drug delivery approaches for breast cancer. Int. J. Nanomedicine, 2017, 12, 6205-6218.
[161]
Gulbake, A.; Jain, S.K. Chitosan: A potential polymer for colon-specific drug delivery system. Expert Opin. Drug Deliv., 2012, 9(6), 713-729.
[162]
Han, L.; Zhao, J.; Zhang, X.; Cao, W.; Hu, X.; Zou, G.; Duan, X.; Liang, X.J. Enhanced siRNA delivery and silencing gold-chitosan nanosystem with surface charge-reversal polymer assembly and good biocompatibility. ACS Nano, 2012, 6(8), 7340-7351.
[163]
Yuan, Y.G.; Peng, Q.L.; Gurunathan, S. Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: combination therapy for effective cancer treatment. Int. J. Nanomedicine, 2017, 12, 6487-6502.
[164]
Yoo, G.; Jeong, S.H.; Ryu, W.I.; Lee, H.; Kim, J.H.; Bae, H.C.; Son, S.W. Gene expression analysis reveals a functional role for the Ag-NPs-induced Egr-1 transcriptional factor in human keratinocytes. Mol. Cell. Toxicol., 2014, 10(2), 149-156.
[165]
Lin, J.; Huang, Z.; Wu, H.; Zhou, W.; Jin, P.; Wei, P.; Zhang, Y.; Zheng, F.; Zhang, J.; Xu, J.; Hu, Y.; Wang, Y.; Li, Y.; Gu, N.; Wen, L. Inhibition of autophagy enhances the anticancer activity of silver nanoparticles. Autophagy, 2014, 10(11), 2006-2020.
[166]
Lin, L.; Xu, Y.; Zhang, S.; Ross, I.M.; Ong, A.C.; Allwood, D.A. Fabrication and luminescence of monolayered boron nitride quantum dots. Small, 2014, 10(1), 60-65.
[167]
AshaRani. P.V.; Low Kah Mun, G.; Hande, M.P.; Valiyaveettil, S. Cytotoxicity and genotoxicity of silver nanoparticles in human cells. ACS Nano, 2009, 3(2), 279-290.
[168]
Sanpui, P.; Chattopadhyay, A.; Ghosh, S.S. Induction of apoptosis in cancer cells at low silver nanoparticle concentrations using chitosan nanocarrier. ACS Appl. Mater. Interfaces, 2011, 3(2), 218-228.
[169]
Gurunathan, S.; Jeong, J.K.; Han, J.W.; Zhang, X.F.; Park, J.H.; Kim, J.H. Multidimensional effects of biologically synthesized silver nanoparticles in Helicobacter pylori, Helicobacter felis, and human lung (L132) and lung carcinoma A549 cells. Nanoscale Res. Lett., 2015, 10, 35.
[170]
Ortega, F.G.; Fernández-Baldo, M.A.; Fernández, J.G.; Serrano, M.J.; Sanz, M.I.; Diaz-Mochón, J.J.; Lorente, J.A.; Raba, J. Study of antitumor activity in breast cell lines using silver nanoparticles produced by yeast. Int. J. Nanomedicine, 2015, 10, 2021-2031.
[171]
Pandey, S.K.; Patel, D.K.; Maurya, A.K.; Thakur, R.; Mishra, D.P.; Vinayak, M.; Haldar, C.; Maiti, P. Corrigendum to Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles. Int. J. Biol. Macromol., 2016, 89, 99-110. Int. J. Biol. Macromol., 2018, 114, 1361.
[172]
Zhang, H.; Liu, G.; Zeng, X.; Wu, Y.; Yang, C.; Mei, L.; Wang, Z.; Huang, L. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells. Int. J. Nanomed, 2015, 10, 2461-2473.
[173]
Bernabeu, E.; Gonzalez, L.; Legaspi, M.J.; Moretton, M.A.; Chiappetta, D.A. Paclitaxel-loaded TPGS-b-PCL nanoparticles: In vitro cytotoxicity and cellular uptake in MCF-7 and MDA-MB-231 cells versus mPEG-b-PCL nanoparticles and Abraxane®. J. Nanosci. Nanotechnol., 2016, 16(1), 160-170.
[174]
Bernabeu, E.; Cagel, M.; Lagomarsino, E.; Moretton, M.; Chiappetta, D.A. Paclitaxel: What has been done and the challenges remain ahead. Int. J. Pharm., 2017, 526(1-2), 474-495.
[175]
Zheng, Y.; Chen, H.; Zeng, X.; Liu, Z.; Xiao, X.; Zhu, Y.; Gu, D.; Mei, L. Surface modification of TPGS-b-(PCL-ran-PGA) nanoparticles with polyethyleneimine as a co-delivery system of TRAIL and endostatin for cervical cancer gene therapy. Nanoscale Res. Lett., 2013, 8(1), 161.
[176]
Jiang, L.; Li, X.; Liu, L.; Zhang, Q. Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer. Nanoscale Res. Lett., 2013, 8(1), 66.
[177]
Yadav, M.K.; Maurya, A.K.; Rajput, G.; Manar, K.K.; Vinayak, M.; Drew, M.G.B.; Singh, N. Synthesis, characterization, DNA binding and cleavage activity of homoleptic zinc(II) β-oxodithioester chelate complexes. J. Coord. Chem., 2017, 70(18), 3171-3185.
[178]
Yadav, M.K.; Maurya, A.K.; Rajput, G.; Manar, K.K.; Vinayak, M.; Drew, M.G.B.; Singh, N. New planar trans-copper(II) β-dithioester chelate complexes: Synthesis, characterization, anticancer activity and DNA-binding/cleavage studies. J. Coord. Chem., 2017, 70(4), 565-583.
[179]
Pool, H.; Quintanar, D.; Figueroa, J.D.; Mano, M.C.; Bechara, J.E.H.; Godinez, L.A.; Mendoza, S. Antioxidant effects of quercetin and catechin encapsulated into PLGA nanoparticles. J. Nanomater., 2012, 2012, 12.
[180]
Jain, A.K.; Thanki, K.; Jain, S. Co-encapsulation of tamoxifen and quercetin in polymeric nanoparticles: Implications on oral bioavailability, antitumor efficacy, and drug-induced toxicity. Mol. Pharm., 2013, 10(9), 3459-3474.
[181]
Balakrishnan, S.; Mukherjee, S.; Das, S.; Bhat, F.A.; Raja Singh, P.; Patra, C.R.; Arunakaran, J. Gold nanoparticles-conjugated quercetin induces apoptosis via inhibition of EGFR/PI3K/Akt-mediated pathway in breast cancer cell lines (MCF-7 and MDA-MB-231). Cell Biochem. Funct., 2017, 35(4), 217-231.
[182]
Sun, M.; Nie, S.; Pan, X.; Zhang, R.; Fan, Z.; Wang, S. Quercetin-nanostructured lipid carriers: Characteristics and anti-breast cancer activities in vitro. Colloids Surf. B Biointerfaces, 2014, 113, 15-24.
[183]
Sarkar, A.; Ghosh, S.; Chowdhury, S.; Pandey, B.; Sil, P.C. Targeted delivery of quercetin loaded mesoporous silica nanoparticles to the breast cancer cells. Biochim. Biophys. Acta, 2016, 1860(10), 2065-2075.
[184]
Aghapour, F.; Moghadamnia, A.A.; Nicolini, A.; Kani, S.N.M.; Barari, L.; Morakabati, P.; Rezazadeh, L.; Kazemi, S. Quercetin conjugated with silica nanoparticles inhibits tumor growth in MCF-7 breast cancer cell lines. Biochem. Biophys. Res. Commun., 2018, 500(4), 860-865.
[185]
Li, J.; Zhang, J.; Wang, Y.; Liang, X.; Wusiman, Z.; Yin, Y.; Shen, Q. Synergistic inhibition of migration and invasion of breast cancer cells by dual docetaxel/quercetin-loaded nanoparticles via Akt/MMP-9 pathway. Int. J. Pharm., 2017, 523(1), 300-309.
[186]
Umrao, S.; Maurya, A.K.; Shukla, V.; Grigoriev, A.; Ahuja, R.; Vinayak, M.; Srivastava, R.R.; Saxena, P.S.; Oh, I.K.; Srivastava, A. Anti-carcinogenic activity of blue fluorescent h-BN quantum dots: As an effective enhancer for dna cleavage activity of anti-cancer drug doxorubicin. Mater. Today Biol., 2019, 1100001
[187]
Cabral, H.; Kataoka, K. Progress of drug-loaded polymeric micelles into clinical studies. J. Control. Release, 2014, 190, 465-476.
[188]
Nishiyama, N.; Matsumura, Y.; Kataoka, K. Development of polymeric micelles for targeting intractable cancers. Cancer Sci., 2016, 107(7), 867-874.
[189]
Soleymani Abyaneh, H.; Vakili, M.R.; Zhang, F.; Choi, P.; Lavasanifar, A. Rational design of block copolymer micelles to control burst drug release at a nanoscale dimension. Acta Biomater., 2015, 24, 127-139.
[190]
Fonge, H.; Huang, H.; Scollard, D.; Reilly, R.M.; Allen, C. Influence of formulation variables on the biodistribution of multifunctional block copolymer micelles. J. Control. Release, 2012, 157(3), 366-374.
[191]
Bae, Y.; Kataoka, K. Intelligent polymeric micelles from functional poly(ethylene glycol)-poly(amino acid) block copolymers. Adv. Drug Deliv. Rev., 2009, 61(10), 768-784.
[192]
Matsukawa, N.; Matsumoto, M.; Shinoki, A.; Hagio, M.; Inoue, R.; Hara, H. Nondigestible saccharides suppress the bacterial degradation of quercetin aglycone in the large intestine and enhance the bioavailability of quercetin glucoside in rats. J. Agric. Food Chem., 2009, 57(20), 9462-9468.
[193]
Miyata, K.; Nishiyama, N.; Kataoka, K. Rational design of smart supramolecular assemblies for gene delivery: Chemical challenges in the creation of artificial viruses. Chem. Soc. Rev., 2012, 41(7), 2562-2574.
[194]
Liu, K.; Chen, W.; Yang, T.; Wen, B.; Ding, D.; Keidar, M.; Tang, J.; Zhang, W. Paclitaxel and quercetin nanoparticles co-loaded in microspheres to prolong retention time for pulmonary drug delivery. Int. J. Nanomed, 2017, 12, 8239-8255.
[195]
Mosqueira, V.C.; Legrand, P.; Gulik, A.; Bourdon, O.; Gref, R.; Labarre, D.; Barratt, G. Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanocapsules. Biomaterials, 2001, 22(22), 2967-2979.
[196]
Murakami, M.; Cabral, H.; Matsumoto, Y.; Wu, S.; Kano, M.R.; Yamori, T.; Nishiyama, N.; Kataoka, K. Improving drug potency and efficacy by nanocarrier-mediated subcellular targeting. Sci. Transl. Med., 2011, 3(64), 64ra2.
[197]
Mochida, Y.; Cabral, H.; Kataoka, K. Polymeric micelles for targeted tumor therapy of platinum anticancer drugs. Expert Opin. Drug Deliv., 2017, 14(12), 1423-1438.
[198]
Takahashi, A.; Yamamoto, Y.; Yasunaga, M.; Koga, Y.; Kuroda, J.; Takigahira, M.; Harada, M.; Saito, H.; Hayashi, T.; Kato, Y.; Kinoshita, T.; Ohkohchi, N.; Hyodo, I.; Matsumura, Y. NC-6300, an epirubicin-incorporating micelle, extends the antitumor effect and reduces the cardiotoxicity of epirubicin. Cancer Sci., 2013, 104(7), 920-925.
[199]
Mukai, H.; Kogawa, T.; Matsubara, N.; Naito, Y.; Sasaki, M.; Hosono, A. A first-in-human Phase 1 study of epirubicin-conjugated polymer micelles (K-912/NC-6300) in patients with advanced or recurrent solid tumors. Invest. New Drugs, 2017, 35(3), 307-314.
[200]
Cabral, H.; Matsumoto, Y.; Mizuno, K.; Chen, Q.; Murakami, M.; Kimura, M.; Terada, Y.; Kano, M.R.; Miyazono, K.; Uesaka, M.; Nishiyama, N.; Kataoka, K. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat. Nanotechnol., 2011, 6(12), 815-823.
[201]
Chintamani; Tandon, M.; Mishra, A.; Agarwal, U.; Saxena, S. Sentinel lymph node biopsy using dye alone method is reliable and accurate even after neo-adjuvant chemotherapy in locally advanced breast cancer--a prospective study. World J. Surg. Oncol., 2011, 9, 19.
[202]
Ahn, H.K.; Jung, M.; Sym, S.J.; Shin, D.B.; Kang, S.M.; Kyung, S.Y.; Park, J.W.; Jeong, S.H.; Cho, E.K. A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in patients with advanced non-small cell lung cancer. Cancer Chemother. Pharmacol., 2014, 74(2), 277-282.
[203]
Vega, J.; Ke, S.; Fan, Z.; Wallace, S.; Charsangavej, C.; Li, C. Targeting doxorubicin to epidermal growth factor receptors by site-specific conjugation of C225 to poly(L-glutamic acid) through a polyethylene glycol spacer. Pharm. Res., 2003, 20(5), 826-832.
[204]
Reddy, S.T.; van der Vlies, A.J.; Simeoni, E.; Angeli, V.; Randolph, G.J.; O’Neil, C.P.; Lee, L.K.; Swartz, M.A.; Hubbell, J.A. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat. Biotechnol., 2007, 25(10), 1159-1164.
[205]
Houdaihed, L.; Evans, J.C.; Allen, C. Overcoming the road blocks: Advancement of block copolymer micelles for cancer therapy in the clinic. Mol. Pharm., 2017, 14(8), 2503-2517.
[206]
Lee, K.S.; Chung, H.C. Im, S.A.; Park, Y.H.; Kim, C.S.; Kim, S.B.; Rha, S.Y.; Lee, M.Y.; Ro, J. Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer. Breast Cancer Res. Treat., 2008, 108(2), 241-250.
[207]
Kim, J.Y.; Do, Y.R.; Song, H.S.; Cho, Y.Y.; Ryoo, H.M.; Bae, S.H.; Kim, J.G.; Chae, Y.S.; Kang, B.W.; Baek, J.H.; Kim, M.K.; Lee, K.H.; Park, K. Multicenter phase II clinical trial of Genexol-PM® with gemcitabine in advanced biliary tract cancer. Anticancer Res., 2017, 37(3), 1467-1473.
[208]
Sutton, D.; Nasongkla, N.; Blanco, E.; Gao, J. Functionalized micellar systems for cancer targeted drug delivery. Pharm. Res., 2007, 24(6), 1029-1046.
[209]
Matsumura, Y. Preclinical and clinical studies of NK012, an SN-38-incorporating polymeric micelles, which is designed based on EPR effect. Adv. Drug Deliv. Rev., 2011, 63(3), 184-192.
[210]
Hamaguchi, T.; Kato, K.; Yasui, H.; Morizane, C.; Ikeda, M.; Ueno, H.; Muro, K.; Yamada, Y.; Okusaka, T.; Shirao, K.; Shimada, Y.; Nakahama, H.; Matsumura, Y. A phase I and pharmacokinetic study of NK105, a paclitaxel-incorporating micellar nanoparticle formulation. Br. J. Cancer, 2007, 97(2), 170-176.
[211]
Matsumura, Y. The drug discovery by nanomedicine and its clinical experience. Jpn. J. Clin. Oncol., 2014, 44(6), 515-525.
[212]
Wilson, R.H.; Plummer, R.; Adam, J.; Eatock, M.M.; Boddy, A.V.; Griffin, M.; Miller, R.; Matsumura, Y.; Shimizu, T.; Calvert, H. Phase I and pharmacokinetic study of NC-6004, a new platinum entity of cisplatin-conjugated polymer forming micelles. J. Clin. Oncol., 2008, 26(Suppl. 15), 2573-2573.
[213]
Wang, C.; Wu, C.; Zhou, X.; Han, T.; Xin, X.; Wu, J.; Zhang, J.; Guo, S. Enhancing cell nucleus accumulation and DNA cleavage activity of anti-cancer drug via graphene quantum dots. Sci. Rep., 2013, 3, 2852.
[214]
Dolatabadi, J.E.N.; Jamali, A. A.; Hasanzadeh, M.; Omidi, Y. Quercetin delivery into cancer cells with single walled carbon nanotubes. Intl. J. Biosci. Biochem. Bioinform., 2011, 21(a), 25.
[215]
Cirillo, G.; Vittorio, O.; Hampel, S.; Iemma, F.; Parchi, P.; Cecchini, M.; Puoci, F.; Picci, N. Quercetin nanocomposite as novel anticancer therapeutic: Improved efficiency and reduced toxicity. Eur. J. Pharm. Sci., 2013, 49(3), 359-365.
[216]
Wang, Q.; Bao, Y.; Ahire, J.; Chao, Y. Co-encapsulation of biodegradable nanoparticles with silicon quantum dots and quercetin for monitored delivery. Adv. Healthc. Mater., 2013, 2(3), 459-466.
[217]
Zhou, X.; Zhang, Y.; Wang, C.; Wu, X.; Yang, Y.; Zheng, B.; Wu, H.; Guo, S.; Zhang, J. Photo-fenton reaction of graphene oxide: A new strategy to prepare graphene quantum dots for DNA cleavage. ACS Nano, 2012, 6(8), 6592-6599.
[218]
Zhang, L.; Xia, J.; Zhao, Q.; Liu, L.; Zhang, Z. Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs. Small, 2010, 6(4), 537-544.
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