Issue 1, 2024

Sensitizing chemotherapy for glioma with fisetin mediated by a microenvironment-responsive nano-drug delivery system

Abstract

Drug resistance has become an obstacle to successful cancer chemotherapies, with therapeutic agents effectively traversing the blood–brain barrier (BBB) remaining a great challenge. A microenvironment responsive and active targeting nanoparticle was constructed to enhance the penetration of drugs, leading to improved therapeutic effects. Dynamic light scattering demonstrated that the prepared nanoparticle had a uniform size. The cRGD modification renders the nanoparticle with active targeting capabilities to traverse the BBB for chemotherapy. The disulfide-bond-containing nanoparticle can be disintegrated in response to a high concentration of endogenous glutathione (GSH) within the tumor microenvironment (TME) for tumor-specific drug release, resulting in more effective accumulation. Notably, the released fisetin further increased the uptake of doxorubicin by glioma cells and exerted synergistic effects to promote apoptosis, induce cellular G2/M cycle arrest, and inhibit cell proliferation and migration in vitro. Moreover, the nanoparticle showed favorable anti-glioma effects in vivo. Our study provides a new strategy to overcome drug resistance by utilizing a natural product to sensitize conventional chemotherapeutics with well-designed targeted nanodelivery systems for cancer treatment.

Graphical abstract: Sensitizing chemotherapy for glioma with fisetin mediated by a microenvironment-responsive nano-drug delivery system

Supplementary files

Article information

Article type
Paper
Submitted
15 Okt. 2023
Accepted
19 Nov. 2023
First published
22 Nov. 2023

Nanoscale, 2024,16, 97-109

Sensitizing chemotherapy for glioma with fisetin mediated by a microenvironment-responsive nano-drug delivery system

W. Wang, Y. Zhang, Y. Jian, S. He, J. Liu, Y. Cheng, S. Zheng, Z. Qian, X. Gao and X. Wang, Nanoscale, 2024, 16, 97 DOI: 10.1039/D3NR05195A

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