Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Research on the Inhibitory Effect of Doxorubicin-loaded Liposomes Targeting GFAP for Glioma Cells

Author(s): Qifeng Li* and Jiaming Xu

Volume 24, Issue 3, 2024

Published on: 02 November, 2023

Page: [177 - 184] Pages: 8

DOI: 10.2174/0118715206265311231030102307

Price: $65

Abstract

Background: Glioma is the most common and devastating brain tumor. In recent years, doxorubicin (DOX) is one of the drugs used in the treatment of gliomas, but it has side effects and poor clinical outcomes. Therefore, the delivery of drugs to the tumor site by targeted transport is a new approach to tumor treatment.

Objective: This study focuses on the anti-tumor effects of GFAP-modified drug-carrying liposomes loaded with DOX (GFAP-DOX-LPs) on gliomas.

Methods: GFAP-DOX-LPs were prepared by solvent evaporation method. After characterization analysis of GFAP-DOX-LPs, the encapsulation efficiency, the drug loading capacity and in vitro release performance were determined. Then, the MTT method was used to investigate the cytotoxicity and proliferative behavior of U251 and U87 cell lines. After that, flow cytometry was used to investigate the effect of the drug administration group on tumor cell apoptosis. Eventually, the anti-tumor activity was tested in vivo.

Results: The average particle size of GFAP-DOX-LPs was determined to be 116.3 ± 6.2 nm, and the average potential was displayed as 22.8 ± 7.2 mv. Besides, the morphology of the particle indicated a spherical shape. The encapsulation rate and drug loading were calculated and determined, which were 91.84 ± 0.41% and 9.27 ± 0.55%. In an acidic medium, the DOX release rate reached about 87%. GFAP-DOX-LPs could target glioma cells with low cytotoxicity and inhibit glioma cell proliferation with high efficiency, resulting in promoting apoptosis. The anti-tumor effect of GFAP-DOX-LPs was significantly enhanced. At the same time, the number of GFAPpositive cells in tumor tissues was significantly lower after treatment. Therefore, the overall survival time could be significantly prolonged.

Conclusion: The prepared GFAP-DOX-LPs had good targeting and glioma cell inhibition ability. This demonstrated the promising application of the prepared liposomes in tumor targeting, especially in the field of targeted drug delivery for the treatment of brain tumor.

« Previous Next »
Graphical Abstract

[1]
Chen, X.; Guo, G.; Lu, Y.; Wang, S.; Zhang, Y.; Huang, Q. Mechanisms and functions of long non coding RNAs in glioma. Oncol. Rep., 2021, 45(4), 9.
[http://dx.doi.org/10.3892/or.2021.7960] [PMID: 33649805]
[2]
Yang, Q.; Zhang, J.; Zhang, X.; Miao, L.; Zhang, W.; Jiang, Z.; Zhou, W. C-C motif chemokine ligand 2/C-C receptor 2 is associated with glioma recurrence and poor survival. Exp. Ther. Med., 2021, 21(6), 564-564.
[http://dx.doi.org/10.3892/etm.2021.9996] [PMID: 33850536]
[3]
Oishi, T.; Koizumi, S.; Kurozumi, K. Molecular mechanisms and clinical challenges of glioma invasion. Brain Sci., 2022, 12(2), 291-291.
[http://dx.doi.org/10.3390/brainsci12020291] [PMID: 35204054]
[4]
Nie, W.; Zan, X.; Yu, T.; Ran, M.; Hong, Z.; He, Y.; Yang, T.; Ju, Y.; Gao, X. Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways. Cell Death Dis., 2020, 11(10), 928.
[http://dx.doi.org/10.1038/s41419-020-03133-1] [PMID: 33116114]
[5]
Niu, W.; Xiao, Q.; Wang, X.; Zhu, J.; Li, J.; Liang, X.; Peng, Y.; Wu, C.; Lu, R.; Pan, Y.; Luo, J.; Zhong, X.; He, H.; Rong, Z.; Fan, J.B.; Wang, Y. A biomimetic drug delivery system by integrating grapefruit extracellular vesicles and doxorubicin-loaded heparin-based nanoparticles for glioma therapy. Nano Lett., 2021, 21(3), 1484-1492.
[http://dx.doi.org/10.1021/acs.nanolett.0c04753] [PMID: 33475372]
[6]
Adam, C.; Bray, T.L.; Pérez-López, A.M.; Tan, E.H.; Rubio-Ruiz, B.; Baillache, D.J.; Houston, D.R.; Salji, M.J.; Leung, H.Y.; Unciti-Broceta, A.A. 5-FU precursor designed to evade anabolic and catabolic drug pathways and activated by pd chemistry in vitro and in vivo. J. Med. Chem., 2022, 65(1), 552-561.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01733] [PMID: 34979089]
[7]
Zhang, H; Yamaguchi, T; Kawabata, K In vitro blood–brain barrier model derived from human iPS cells and its applications. Recent Adv. iPSC Technol, 2021, 5, 63-85.
[8]
Fabel, K.; Dietrich, J.; Hau, P.; Wismeth, C.; Winner, B.; Przywara, S.; Steinbrecher, A.; Ullrich, W.; Bogdahn, U. Long-term stabilization in patients with malignant glioma after treatment with liposomal doxorubicin. Cancer, 2001, 92(7), 1936-1942.
[http://dx.doi.org/10.1002/1097-0142(20011001)92:7<1936:AID-CNCR1712>3.0.CO;2-H] [PMID: 11745268]
[9]
Zhang, M.; Lou, C.; Cao, A. Progresses on active targeting liposome drug delivery systems for tumor therapy. Sheng Wu I Hsueh Kung Cheng Hsueh Tsa Chih, 2022, 39(3), 633-638.
[PMID: 35788534]
[10]
Zhao, Y.Q.; Li, L.J.; Zhou, E.F.; Wang, J-Y.; Wang, Y.; Guo, L-M.; Zhang, X-X. Lipid-based nanocarrier systems for drug delivery: Advances and applications. Pharm. Fronts, 2022, 4(2), e43-e60.
[http://dx.doi.org/10.1055/s-0042-1751036]
[11]
Chopra, S.; Venkatesan, N.; Betageri, G.V. Liposomes as nanocarriers for anti-HIV therapy. Drug Deliv. Transl. Res., 2013, 3(5), 471-478.
[http://dx.doi.org/10.1007/s13346-013-0134-2] [PMID: 25788354]
[12]
Alrbyawi, H.; Poudel, I.; Annaji, M.; Arnold, R.D.; Tiwari, A.K.; Babu, R.J. Recent advancements of stimuli-responsive targeted liposomal formulations for cancer drug delivery. Pharm. Nanotechnol., 2022, 10(1), 3-23.
[http://dx.doi.org/10.2174/2211738510666220214102626] [PMID: 35156590]
[13]
Maruyama, M.; Tojo, H.; Toi, K.; Ienaka, Y.; Hyodo, K.; Kikuchi, H.; Ogawara, K.; Higaki, K. Effect of doxorubicin release rate from polyethylene glycol-modified liposome on anti-tumor activity in B16-BL6 tumor-bearing mice. J. Pharm. Sci., 2022, 111(2), 293-297.
[http://dx.doi.org/10.1016/j.xphs.2021.11.020] [PMID: 34861247]
[14]
Minamisakamoto, T.; Nishiguchi, S.; Hashimoto, K.; Ogawara, K.; Maruyama, M.; Higaki, K. Sequential administration of PEG-Span 80 niosome enhances anti-tumor effect of doxorubicin-containing PEG liposome. Eur. J. Pharm. Biopharm., 2021, 169, 20-28.
[http://dx.doi.org/10.1016/j.ejpb.2021.08.013] [PMID: 34461216]
[15]
Huang, X.; Chen, L.; Zhang, Y.; Zhou, S.; Cai, H.H.; Li, T.; Jin, H.; Cai, J.; Zhou, H.; Pi, J. GE11 peptide conjugated liposomes for EGFR-Targeted and chemophotothermal combined anticancer therapy. Bioinorg. Chem. Appl., 2021, 2021(31), 1-15.
[http://dx.doi.org/10.1155/2021/5534870] [PMID: 33868396]
[16]
Bodegraven, E.J.; Sluijs, J.A.; Tan, A.K.; Robe, P.A.J.T.; Hol, E.M. New GFAP splice isoform (GFAPµ) differentially expressed in glioma translates into 21 kDa N‐terminal GFAP protein. FASEB J., 2021, 35(3), e21389-e21389.
[http://dx.doi.org/10.1096/fj.202001767R] [PMID: 33583081]
[17]
Chekhonin, V.P.; Baklaushev, V.P.; Yusubalieva, G.M.; Belorusova, A.E.; Gulyaev, M.V.; Tsitrin, E.B.; Grinenko, N.F.; Gurina, O.I.; Pirogov, Y.A. Targeted delivery of liposomal nanocontainers to the peritumoral zone of glioma by means of monoclonal antibodies against GFAP and the extracellular loop of Cx43. Nanomedicine, 2012, 8(1), 63-70.
[http://dx.doi.org/10.1016/j.nano.2011.05.011] [PMID: 21703991]
[18]
Pan, B.; Li, P.; Chen, J.; Sun, J.; Huang, N. Study on the effect and mechanism of paclitaxel-succinic acid drug-loaded nanofibers in treating lung cancer. J. Nanosci. Nanotechnol., 2021, 21(2), 909-913.
[http://dx.doi.org/10.1166/jnn.2021.18649] [PMID: 33183423]
[19]
Sun, W.; Chen, G.; Du, F.; Li, X. Targeted drug delivery to cancer stem cells through nanotechnological approaches. Curr. Stem Cell Res. Ther., 2021, 16(4), 367-384.
[http://dx.doi.org/10.2174/1574888X15999201001204727] [PMID: 33023455]
[20]
Sonker, M.; Bajpai, S.; Khan, M.A.; Yu, X.; Tiwary, S.K.; Shreyash, N. Review of recent advances and their improvement in the effectiveness of hydrogel-based targeted drug delivery: A hope for treating cancer. ACS Appl. Bio Mater., 2021, 4(12), 8080-8109.
[http://dx.doi.org/10.1021/acsabm.1c00857] [PMID: 35005919]
[21]
Meng, L.; Wang, C.; Lu, Y.; Sheng, G.; Yang, L.; Wu, Z.; Xu, H.; Han, C.; Lu, Y.; Han, F. Targeted regulation of blood–brain barrier for enhanced therapeutic efficiency of hypoxia-modifier nanoparticles and immune checkpoint blockade antibodies for glioblastoma. ACS Appl. Mater. Interfaces, 2021, 13(10), 11657-11671.
[http://dx.doi.org/10.1021/acsami.1c00347] [PMID: 33684289]
[22]
Vatutin, M.T.; Sklyannaya, E.V.; El-Khatib, M.A. Hepatotoxicity of chemotherapeutic agents. Curr. State Problem, 2016, 21(6), 325-333.
[23]
Shivapriya, G.; Bhagavathy, S. Formulation, characterization and in vitro drug delivery of vitexin loaded liposomes. Int. J. Pharm. Sci. Technol., 2021, 16(6), 637-644.
[24]
Singh, A.; Srivastava, A.; Gupta, A. Liposomal drug delivery system – a review. J. Appl. Pharm. Sci. Res., 2020, 3(3), 07-10.
[http://dx.doi.org/10.31069/japsr.v3i3.2]
[25]
Gorbik, V.S.; Shprakh, Z.S.; Kozlova, Z.M.; Salova, V.G. Liposomes as a targeted delivery system of drugs. Russian J. Biother., 2021, 20(1), 33-41.
[http://dx.doi.org/10.17650/1726-9784-2021-20-1-33-41]
[26]
Yan, H.; Wei, P.; Song, J.; Jia, X.; Zhang, Z. Enhanced anticancer activity in vitro and in vivo of luteolin incorporated into long-circulating micelles based on DSPE-PEG2000 and TPGS. J. Pharm. Pharmacol., 2016, 68(10), 1290-1298.
[http://dx.doi.org/10.1111/jphp.12598] [PMID: 27465923]
[27]
Zhang, J.; He, Y.; Jiang, J.; Li, M.; Jin, C.; Wang, L.; Wang, D. In vitro and in vivo evaluation of folate-mediated PEGylated nanostructured lipid carriers for the efficient delivery of furanodiene. Drug Dev. Ind. Pharm., 2017, 43(10), 1610-1618.
[http://dx.doi.org/10.1080/03639045.2017.1328429] [PMID: 28481661]
[28]
Feng, L.; Saulsbury, M.; Heyliger, S. Abstract 5538: A pH-responsive doxorubicin-lipid conjugate loaded nanomedicine for breast cancer treatment. Cancer Res., 2015, 75(15), 5538-5538.
[29]
Fang, C.; Shi, B.; Pei, Y. Effect of MePEG molecular weight and particle size on in vitro release of tumor necrosis factor-α-loaded nanoparticles1. Acta Pharmacol. Sin., 2005, 26(2), 242-249.
[http://dx.doi.org/10.1111/j.1745-7254.2005.00537.x] [PMID: 15663906]
[30]
Sokolova, V.; Nzou, G.; van der Meer, S.B.; Ruks, T.; Heggen, M.; Loza, K.; Hagemann, N.; Murke, F.; Giebel, B.; Hermann, D.M.; Atala, A.J.; Epple, M. Ultrasmall gold nanoparticles (2 nm) can penetrate and enter cell nuclei in an in vitro 3D brain spheroid model. Acta Biomater., 2020, 111(15), 349-362.
[http://dx.doi.org/10.1016/j.actbio.2020.04.023] [PMID: 32413579]
[31]
Grossi, C.; Guccione, C.; Isacchi, B.; Bergonzi, M.C.; Luccarini, I.; Casamenti, F.; Bilia, A.R. Development of blood-brain barrier permeable nanoparticles as potential carriers for salvianolic acid B to CNS. Planta Med., 2017, 83(5), 382-391.
[PMID: 27002395]
[32]
Sydow, K.; Nikolenko, H.; Lorenz, D.; Müller, R.H.; Dathe, M. Lipopeptide-based micellar and liposomal carriers: Influence of surface charge and particle size on cellular uptake into blood brain barrier cells. Eur. J. Pharm. Biopharm., 2016, 109, 130-139.
[http://dx.doi.org/10.1016/j.ejpb.2016.09.019] [PMID: 27702684]
[33]
Simón-Vázquez, R.; Tsapis, N.; Lorscheider, M.; Rodríguez, A.; Calleja, P.; Mousnier, L.; de Miguel Villegas, E.; González-Fernández, Á.; Fattal, E. Improving dexamethasone drug loading and efficacy in treating arthritis through a lipophilic prodrug entrapped into PLGA-PEG nanoparticles. Drug Deliv. Transl. Res., 2022, 12(5), 1270-1284.
[http://dx.doi.org/10.1007/s13346-021-01112-3] [PMID: 34993924]
[34]
Cheng, Q.F.; Qian, H.Q.; Zhang, D.H.; Huang, Y.; Sha, H.Z.; Liu, B.R. Evaluation for preparation and anticancer efficacy in vitro of drug-loaded nanoerythrosomes. Zhongguo Zhongyao Zazhi, 2016, 41(11), 2093-2097.
[PMID: 28901106]
[35]
Wu, Q.; Liu, D.; Zhang, X.; Wang, D. DongYe, M.; Chen, W.; Lin, D.; Zhu, F.; Chen, W.; Lin, H. Development and effects of tacrolimus-loaded nanoparticles on the inhibition of corneal allograft rejection. Drug Deliv., 2019, 26(1), 290-299.
[http://dx.doi.org/10.1080/10717544.2019.1582728] [PMID: 30895841]
[36]
Zhao, X.; Li, J.; Cheng, S.; Li, S.; Bai, X.; Xi, J. Study on the role of paclitaxel nano-drug delivery system in inhibiting intimal hyperplasia and improving vascular remodeling in abdominal aortic injury model. J. Nanosci. Nanotechnol., 2021, 21(2), 1385-1389.
[http://dx.doi.org/10.1166/jnn.2021.18653] [PMID: 33183488]
[37]
Di Gregorio, E.; Romiti, C.; Di Lorenzo, A.; Cavallo, F.; Ferrauto, G.; Conti, L. RGD_PLGA nanoparticles with docetaxel: A route for improving drug efficiency and reducing toxicity in breast cancer treatment. Cancers, 2022, 15(1), 8.
[http://dx.doi.org/10.3390/cancers15010008] [PMID: 36612006]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy