Overcoming multidrug resistance by reversan and exterminating glioblastoma and glioblastoma stem cells by delivering drug-loaded nanostructure hybrid lipid capsules (nHLCs).

Autor: Hasan U; Department of Biotechnology, Indian Institute of Technology, Hyderabad, India.; Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India., Chauhan M; Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India., Basu SM; Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India., R J; Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India., Giri J; Department of Biomedical Engineering, Indian Institute of Technology, Hyderabad, India. jgiri@iith.ac.in.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 Feb; Vol. 14 (2), pp. 342-359. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1007/s13346-023-01401-z
Abstrakt: Glioblastoma multiforme (GBM) is regarded as a highly aggressive brain cancer with a poor prognosis. There is an increase in the expression of P-glycoprotein (P-gp), responsible for multidrug resistance (MDR), making it a potential target for improving drug responses. Additionally, glioblastoma stem cells (GSCs) increase resistance to chemo- and radiotherapy and play a major role in cancer relapse. In this study, we targeted P-gp using a small molecule inhibitor, reversan (RV), to inhibit MDR that prolonged the retention of drugs in the cytosolic milieu. To eliminate GBM and GSCs, we have used two well-established anti-cancer drugs, regorafenib (RF) and curcumin (CMN). To improve the pharmacokinetics and decrease systemic delivery of drugs, we developed nanostructure hybrid lipid capsules (nHLCs), where hydrophobic drugs can be loaded in the core, and their physicochemical properties were determined by dynamic light scattering (DLS) and cryo-scanning electron microscopy (SEM). Inhibition of MDR by RV has also shown enhanced retention of nHLC in GBM cells. Co-delivery of drug-loaded nHLCs, pre-treated with RV, exhibited superior cytotoxicity in both GBM and GSCs than their individual doses and effectively reduced the size and stemness of tumor spheres and accelerated the rate of apoptosis, suggesting a promising treatment for glioblastoma.
(© 2023. Controlled Release Society.)
Databáze: MEDLINE
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