Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Perspective

Saponins-uptake and Targeting Issues for Brain-specific Delivery for Enhanced Cell Death Induction in Glioblastoma

Author(s): P.K. Suresh*

Volume 19, Issue 6, 2022

Published on: 31 March, 2022

Page: [473 - 480] Pages: 8

DOI: 10.2174/1570180819666220121145332

Abstract

Saponins represent a category of diverse, natural glycoside molecules that belong to the triterpenoid or the steroid class. They vary in terms of their solubility and permeability characteristics and are classifiable based on the biopharmaceutics classification system. They have drug delivery potential as surfactants that can solubilize cholesterol in the plasma membrane of tumorigenic cells. Glioblastoma is an important malignancy that can aggressively afflict the brain of humans with a poor prognosis. Glioblastoma Stem Cells (GSCs) are an important subset of cancer cells and major determinants for drug resistance and tumour relapse. These cells are quiescent and have been known to survive current therapeutic strategies. Certain saponins have shown potential to eliminate glioblastoma cells in a variety of model systems and hence provide a sound scientific basis for their development as a “stand-alone” drug or as part of a drug combination (from the existing arsenal of drugs) developed for the treatment of glioblastoma. However, due to their reactogenicity towards the immune system and hemolytic potential, selective delivery to the tumorigenic site is essential. Hence, nano-formulations (liposome/emulsion-based delivery systems/nano-structured lipid and calix[n]arenes-based carriers) and variants that are resistant to saponin may serve as delivery tools that can be functionalized to improve the selectivity. It is necessary to develop/ validate/refine in vitro higher order models that replicate the features of the glioma microenvironment (BBB/BTB). Reproducible validation of the model as well as the drug/delivery system will help in the development of formulations that can augment cell death in this recalcitrant brain tumour.

Keywords: Saponins, liposomes, targeting, brain-specific delivery, cell death, glioblastoma.

Next »
Graphical Abstract

[1]
Han, J.; Shen, X.; Zhang, Y.; Wang, S.; Zhou, L. Astragaloside IV suppresses transforming growth factor-β1-induced epithelial-mesenchymal transition through inhibition of Wnt/β-catenin pathway in glioma U251 cells. Biosci. Biotechnol. Biochem., 2020, 84(7), 1345-1352.
[http://dx.doi.org/10.1080/09168451.2020.1737502] [PMID: 32154763]
[2]
Dai, Z.; Liu, H.; Wang, B.; Yang, D.; Zhu, Y.Y.; Yan, H.; Zhu, P.F.; Liu, Y.P.; Chen, H.C.; Zhao, Y.L.; Zhao, L.X.; Zhao, X.D.; Liu, H.Y.; Luo, X.D. Structures/cytotoxicity/selectivity relationship of natural steroidal saponins against GSCs and primary mechanism of tribulosaponin A. Eur. J. Med. Chem., 2021, 210, 113068.
[http://dx.doi.org/10.1016/j.ejmech.2020.113068] [PMID: 33310292]
[3]
Zhang, S.; Lu, Y.; Li, H.; Ji, Y.; Fang, F.; Tang, H.; Qiu, P. A steroidal saponin form Paris vietnamensis (Takht.) reverses temozolomide resistance in glioblastoma cells via inducing apoptosis through ROS/PI3K/Akt pathway. Biosci. Trends, 2020, 14(2), 123-133.
[http://dx.doi.org/10.5582/bst.2020.01005] [PMID: 32173672]
[4]
Prados, M.D.; Byron, S.A.; Tran, N.L.; Phillips, J.J.; Molinaro, A.M.; Ligon, K.L.; Wen, P.Y.; Kuhn, J.G.; Mellinghoff, I.K.; de Groot, J.F.; Colman, H.; Cloughesy, T.F.; Chang, S.M.; Ryken, T.C.; Tembe, W.D.; Kiefer, J.A.; Berens, M.E.; Craig, D.W.; Carpten, J.D.; Trent, J.M. Toward precision medicine in glioblastoma: The promise and the challenges. Neuro-oncol., 2015, 17(8), 1051-1063.
[http://dx.doi.org/10.1093/neuonc/nov031] [PMID: 25934816]
[5]
Pang, D.; Li, C.; Yang, C.; Zou, Y.; Feng, B.; Li, L.; Liu, W.; Geng, Y.; Luo, Q.; Chen, Z.; Huang, C. Polyphyllin VII promotes apoptosis and autophagic cell death via ROS-inhibited AKT activity, and sensitizes glioma cells to temozolomide. Oxid. Med. Cell. Longev., 2019, 2019, 1805635.
[http://dx.doi.org/10.1155/2019/1805635] [PMID: 31814867]
[6]
Hong, J.M.; Kim, J.H.; Kim, H.; Lee, W.J.; Hwang, Y.I. SB365, Pulsatilla saponin D induces caspase-independent cell death and augments the anticancer effect of temozolomide in glioblastoma multiforme cells. Molecules, 2019, 24(18), 3230.
[http://dx.doi.org/10.3390/molecules24183230] [PMID: 31491945]
[7]
Chen, Z.; Wei, X.; Shen, L.; Zhu, H.; Zheng, X. 20(S)-ginsenoside-Rg3 reverses temozolomide resistance and restrains epithelial-mesenchymal transition progression in glioblastoma. Cancer Sci., 2019, 110(1), 389-400.
[http://dx.doi.org/10.1111/cas.13881] [PMID: 30431207]
[8]
Moskwa, J.; Naliwajko, S.K.; Markiewicz-Żukowska, R.; Gromkowska-Kępka, K.J.; Nowakowski, P.; Strawa, J.W.; Borawska, M.H.; Tomczyk, M.; Socha, K. Chemical composition of Polish propolis and its antiproliferative effect in combination with Bacopa monnieri on glioblastoma cell lines. Sci. Rep., 2020, 10(1), 21127.
[http://dx.doi.org/10.1038/s41598-020-78014-w] [PMID: 33273550]
[9]
Kim, T.J.; Kim, H.J.; Kang, M.; Cho, J.H.; Kim, Y.G.; Lee, S.M.; Byun, J.S.; Kim, D.Y. Ginsenoside F2 induces cellular toxicity to glioblastoma through the impairment of mitochondrial function. Phytomedicine, 2021, 83, 153483.
[http://dx.doi.org/10.1016/j.phymed.2021.153483] [PMID: 33578358]
[10]
Lee, S.; Kwon, M.C.; Jang, J.P.; Sohng, J.K.; Jung, H.J. The ginsenoside metabolite compound K inhibits growth, migration and stemness of glioblastoma cells. Int. J. Oncol., 2017, 51(2), 414-424.
[http://dx.doi.org/10.3892/ijo.2017.4054] [PMID: 28656196]
[11]
Harford-Wright, E.; Bidère, N.; Gavard, J. β-escin selectively targets the glioblastoma-initiating cell population and reduces cell viability. Oncotarget, 2016, 7(41), 66865-66879.
[http://dx.doi.org/10.18632/oncotarget.11784] [PMID: 27589691]
[12]
Sherer, C.; Snape, T.J. Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives. Eur. J. Med. Chem., 2015, 97, 552-560.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.007] [PMID: 25466446]
[13]
Issa, S.; Prandina, A.; Bedel, N.; Rongved, P.; Yous, S.; Le Borgne, M.; Bouaziz, Z. Carbazole scaffolds in cancer therapy: A review from 2012 to 2018. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1321-1346.
[http://dx.doi.org/10.1080/14756366.2019.1640692] [PMID: 31328585]
[14]
Roesch, S.; Fermi, V.; Rominger, F.; Herold-Mende, C.; Romero-Nieto, C. Gold(i) complexes based on six-membered phosphorus heterocycles as bio-active molecules against brain cancer. Chem. Commun. (Camb.), 2020, 56(93), 14593-14596. Gold(I) complexes based on six-membered phosphorus heterocycles as bio-active molecules against brain cancer. Chem. Commun. (Camb.), 2020, 56(95), 15088. Erratum for. Chem. Commun. (Camb.), 2020, 56(93), 14593-14596.
[http://dx.doi.org/10.1039/D0CC05761D] [PMID: 33124620]
[15]
Zhang, Y.; Xi, K.; Fu, X.; Sun, H.; Wang, H.; Yu, D.; Li, Z.; Ma, Y.; Liu, X.; Huang, B.; Wang, J.; Li, G.; Cui, J.; Li, X.; Ni, S. Versatile metal-phenolic network nanoparticles for multitargeted combination therapy and magnetic resonance tracing in glioblastoma. Biomaterials, 2021, 278, 121163.
[http://dx.doi.org/10.1016/j.biomaterials.2021.121163] [PMID: 34601197]
[16]
Zhang, H.; Wang, R.; Yu, Y.; Liu, J.; Luo, T.; Fan, F. Glioblastoma treatment modalities besides surgery. J. Cancer, 2019, 10(20), 4793-4806.
[http://dx.doi.org/10.7150/jca.32475] [PMID: 31598150]
[17]
Jie, M.; Mao, S.; Liu, H.; He, Z.; Li, H.F.; Lin, J.M. Evaluation of drug combination for glioblastoma based on an intestine-liver metabolic model on microchip. Analyst (Lond.), 2017, 142(19), 3629-3638.
[http://dx.doi.org/10.1039/C7AN00453B] [PMID: 28853486]
[18]
Sudimack, J.J.; Guo, W.; Tjarks, W.; Lee, R.J. A novel pH-sensitive liposome formulation containing oleyl alcohol. Biochim. Biophys. Acta, 2002, 1564(1), 31-37.
[http://dx.doi.org/10.1016/S0005-2736(02)00399-1] [PMID: 12100993]
[19]
Li, T.; Shu, Y.J.; Cheng, J.Y.; Liang, R.C.; Dian, S.N.; Lv, X.X.; Yang, M.Q.; Huang, S.L.; Chen, G.; Yang, F. Pharmacokinetics and efficiency of brain targeting of ginsenosides Rg1 and Rb1 given as Nao-Qing microemulsion. Drug Dev. Ind. Pharm., 2015, 41(2), 224-231.
[http://dx.doi.org/10.3109/03639045.2013.858734] [PMID: 24237326]
[20]
Wang, Y.; Shen, J.; Yang, X.; Jin, Y.; Yang, Z.; Wang, R.; Zhang, F.; Linhardt, R.J. Mechanism of enhanced oral absorption of akebia saponin D by a self-nanoemulsifying drug delivery system loaded with phospholipid complex. Drug Dev. Ind. Pharm., 2019, 45(1), 124-129.
[http://dx.doi.org/10.1080/03639045.2018.1526183] [PMID: 30229685]
[21]
Hao, F.; He, Y.; Sun, Y.; Zheng, B.; Liu, Y.; Wang, X.; Zhang, Y.; Lee, R.J.; Teng, L.; Xie, J. Improvement of oral availability of ginseng fruit saponins by a proliposome delivery system containing sodium deoxycholate. Saudi J. Biol. Sci., 2016, 23(1), S113-S125.
[http://dx.doi.org/10.1016/j.sjbs.2015.09.024] [PMID: 26858556]
[22]
Zwain, T.; Alder, J.E.; Sabagh, B.; Shaw, A.; Burrow, A.J.; Singh, K.K. Tailoring functional nanostructured lipid carriers for glioblastoma treatment with enhanced permeability through in-vitro 3D BBB/BBTB models. Mater. Sci. Eng. C, 2021, 121, 111774.
[http://dx.doi.org/10.1016/j.msec.2020.111774] [PMID: 33579439]
[23]
Su, X.; Zhang, D.; Zhang, H.; Zhao, K.; Hou, W. Preparation and characterization of angiopep-2 functionalized Ginsenoside-Rg3 loaded nanoparticles and the effect on C6 Glioma cells. Pharm. Dev. Technol., 2020, 25(3), 385-395.
[http://dx.doi.org/10.1080/10837450.2018.1551901] [PMID: 30601070]
[24]
Albertini, B.; Mathieu, V.; Iraci, N.; Van Woensel, M.; Schoubben, A.; Donnadio, A.; Greco, S.M.L.; Ricci, M.; Temperini, A.; Blasi, P.; Wauthoz, N. Tumor targeting by peptide-decorated gold nanoparticles. Mol. Pharm., 2019, 16(6), 2430-2444.
[http://dx.doi.org/10.1021/acs.molpharmaceut.9b00047] [PMID: 30969129]
[25]
van Tellingen, O.; Yetkin-Arik, B.; de Gooijer, M.C.; Wesseling, P.; Wurdinger, T.; de Vries, H.E. Overcoming the blood-brain tumor barrier for effective glioblastoma treatment. Drug Resist. Updat., 2015, 19, 1-12.
[http://dx.doi.org/10.1016/j.drup.2015.02.002] [PMID: 25791797]
[26]
Goyal, K.; Konar, A.; Kumar, B.S.H.; Koul, V. Lactoferrin-conjugated pH and redox-sensitive polymersomes based on PEG-S-S-PLA-PCL-OH boost delivery of bacosides to the brain. Nanoscale, 2018, 10(37), 17781-17798.
[http://dx.doi.org/10.1039/C8NR03828G] [PMID: 30215650]
[27]
Naseer, M.M.; Ahmed, M.; Hameed, S. Functionalized calix[4]arenes as potential therapeutic agents. Chem. Biol. Drug Des., 2017, 89(2), 243-256.
[http://dx.doi.org/10.1111/cbdd.12818] [PMID: 28205403]
[28]
Gallego-Yerga, L.; de la Torre, C.; Sansone, F.; Casnati, A.; Mellet, C.O.; García Fernández, J.M.; Ceña, V. Synthesis, self-assembly and anticancer drug encapsulation and delivery properties of cyclodextrin-based giant amphiphiles. Carbohydr. Polym., 2021, 252, 117135.
[http://dx.doi.org/10.1016/j.carbpol.2020.117135] [PMID: 33183594]
[29]
Basilotta, R.; Mannino, D.; Filippone, A.; Casili, G.; Prestifilippo, A.; Colarossi, L.; Raciti, G.; Esposito, E.; Campolo, M. Role of calixarene in chemotherapy delivery strategies. Molecules, 2021, 26(13), 3963.
[http://dx.doi.org/10.3390/molecules26133963] [PMID: 34209495]
[30]
Renziehausen, A.; Tsiailanis, A.D.; Perryman, R.; Stylos, E.K.; Chatzigiannis, C.; O’Neill, K.; Crook, T.; Tzakos, A.G.; Syed, N. Encapsulation of temozolomide in a calixarene nanocapsule improves its stability and enhances its therapeutic efficacy against glioblastoma. Mol. Cancer Ther., 2019, 18(9), 1497-1505.
[http://dx.doi.org/10.1158/1535-7163.MCT-18-1250] [PMID: 31213505]
[31]
Nederman, T.; Norling, B.; Glimelius, B.; Carlsson, J.; Brunk, U. Demonstration of an extracellular matrix in multicellular tumor spheroids. Cancer Res., 1984, 44(7), 3090-3097.
[PMID: 6373002]
[32]
De Witt Hamer, P.C.; Van Tilborg, A.A.; Eijk, P.P.; Sminia, P.; Troost, D.; Van Noorden, C.J.; Ylstra, B.; Leenstra, S. The genomic profile of human malignant glioma is altered early in primary cell culture and preserved in spheroids. Oncogene, 2008, 27(14), 2091-2096.
[http://dx.doi.org/10.1038/sj.onc.1210850] [PMID: 17934519]
[33]
Mirab, F.; Kang, Y.J.; Majd, S. Preparation and characterization of size-controlled glioma spheroids using agarose hydrogel microwells. PLoS One, 2019, 14(1), e0211078.
[http://dx.doi.org/10.1371/journal.pone.0211078] [PMID: 30677075]
[34]
Polano, M.; Fabbiani, E.; Adreuzzi, E.; Cintio, F.D.; Bedon, L.; Gentilini, D.; Mongiat, M.; Ius, T.; Arcicasa, M.; Skrap, M.; Dal Bo, M.; Toffoli, G. A new epigenetic model to stratify glioma patients according to their immunosuppressive state. Cells, 2021, 10(3), 576.
[http://dx.doi.org/10.3390/cells10030576] [PMID: 33807997]
[35]
Turnovcova, K.; Marekova, D.; Sursal, T.; Krupova, M.; Gandhi, R.; Krupa, P.; Kaiser, R.; Herynek, V.; Netuka, D.; Jendelova, P.; Jhanwar-Uniyal, M. Understanding the biological basis of glioblastoma patient-derived spheroids. Anticancer Res., 2021, 41(3), 1183-1195.
[http://dx.doi.org/10.21873/anticanres.14875] [PMID: 33788709]
[36]
Yi, H.G.; Jeong, Y.H.; Kim, Y.; Choi, Y.J.; Moon, H.E.; Park, S.H.; Kang, K.S.; Bae, M.; Jang, J.; Youn, H.; Paek, S.H.; Cho, D.W. A bioprinted human-glioblastoma-on-a-chip for the identification of patient-specific responses to chemoradiotherapy. Nat. Biomed. Eng., 2019, 3(7), 509-519.
[http://dx.doi.org/10.1038/s41551-019-0363-x] [PMID: 31148598]
[37]
Gerigk, M.; Bulstrode, H.; Shi, H.H.; Tönisen, F.; Cerutti, C.; Morrison, G.; Rowitch, D.; Huang, Y.Y.S. On-chip perivascular niche supporting stemness of patient-derived glioma cells in a serum-free, flowable culture. Lab Chip, 2021, 21(12), 2343-2358.
[http://dx.doi.org/10.1039/D1LC00271F] [PMID: 33969368]
[38]
Hubert, C.G.; Rivera, M.; Spangler, L.C.; Wu, Q.; Mack, S.C.; Prager, B.C.; Couce, M.; McLendon, R.E.; Sloan, A.E.; Rich, J.N. A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo. Cancer Res., 2016, 76(8), 2465-2477.
[http://dx.doi.org/10.1158/0008-5472.CAN-15-2402] [PMID: 26896279]
[39]
Wang, X.; Li, X.; Dai, X.; Zhang, X.; Zhang, J.; Xu, T.; Lan, Q. Coaxial extrusion bioprinted shell-core hydrogel microfibers mimic glioma microenvironment and enhance the drug resistance of cancer cells. Colloids Surf. B Biointerfaces, 2018, 171, 291-299.
[http://dx.doi.org/10.1016/j.colsurfb.2018.07.042] [PMID: 30048904]
[40]
Linkous, A.; Balamatsias, D.; Snuderl, M.; Edwards, L.; Miyaguchi, K.; Milner, T.; Reich, B.; Cohen-Gould, L.; Storaska, A.; Nakayama, Y.; Schenkein, E.; Singhania, R.; Cirigliano, S.; Magdeldin, T.; Lin, Y.; Nanjangud, G.; Chadalavada, K.; Pisapia, D.; Liston, C.; Fine, H.A. Modeling patient-derived glioblastoma with cerebral organoids. Cell Rep., 2019, 26(12), 3203-3211.e5.
[http://dx.doi.org/10.1016/j.celrep.2019.02.063] [PMID: 30893594]
[41]
Thakur, A.; Sidu, R.K.; Zou, H.; Alam, M.K.; Yang, M.; Lee, Y. Inhibition of glioma cells’ proliferation by doxorubicin-loaded exosomes via microfluidics. Int. J. Nanomedicine, 2020, 15, 8331-8343.
[http://dx.doi.org/10.2147/IJN.S263956] [PMID: 33149579]
[42]
MacLeod, G.; Bozek, D.A.; Rajakulendran, N.; Monteiro, V.; Ahmadi, M.; Steinhart, Z.; Kushida, M.M.; Yu, H.; Coutinho, F.J.; Cavalli, F.M.G.; Restall, I.; Hao, X.; Hart, T.; Luchman, H.A.; Weiss, S.; Dirks, P.B.; Angers, S. Genome-wide CRISPR-Cas9 screens expose genetic vulnerabilities and mechanisms of temozolomide sensitivity in glioblastoma stem cells. Cell Rep., 2019, 27(3), 971-986.e9.
[http://dx.doi.org/10.1016/j.celrep.2019.03.047] [PMID: 30995489]

Rights & Permissions Print Cite
Article Metrics
18
1
© 2024 Bentham Science Publishers | Privacy Policy