Issue 21, 2019

An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance

Abstract

Multi-drug resistance (MDR) of tumor cells has greatly hindered the therapeutic efficacy of chemotherapeutic drugs, resulting in chemotherapy failure, while overexpression of ATP-binding cassette (ABC) transporters in cell membranes is the leading cause of MDR. In this study, we reported novel self-assembled triphenylphosphine-quercetin–polyethylene glycol–monoclonal antibody nanoparticles (TQ–PEG–mAb NPs) for overcoming MDR primarily through mitochondrial damage to block ATP supply to ABC transporters both in vitro and in vivo. The doxorubicin (DOX)-loaded NPs (TQ/DOX–PEG–mAb) were composed of two drugs (TQ and DOX) and an outer shielding shell of the PEG–mAb conjugate. Besides, the outer shell could be acid-responsively detached to expose the positive charge of TQ inside the NPs to enhance cellular uptake. TQ was proved to effectively induce mitochondrial damage with increased ROS levels and depolarization of mitochondrial membrane potential (MMP), leading to prominently reduced ATP supply to ABC transporters. Moreover, the involvement of the anti-vascular endothelial growth factor (VEGF) mAb was not only for efficient targeting but also for combined therapy. Consequently, TQ/DOX–PEG–mAb showed that the internalized amount of DOX was largely improved while the efflux amount was dramatically inhibited on MCF-7/ADR cells, indicating excellent reversal of DOX resistance. Importantly, the growth of DOX-resistant breast tumors was significantly inhibited with no evident systemic toxicity. Therefore, the employment of TQ–PEG–mAb is believed to be a new approach to improve the efficacy of chemotherapeutic drugs in MDR tumors.

Graphical abstract: An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance

Supplementary files

Article information

Article type
Paper
Submitted
22 Feb 2019
Accepted
03 Apr 2019
First published
16 Apr 2019
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2019,9, 12110-12123

An energy-blocking nanoparticle decorated with anti-VEGF antibody to reverse chemotherapeutic drug resistance

L. Gu, P. Cui, L. Xing, Y. He, X. Chang, T. Zhou, Y. Liu, L. Li and H. Jiang, RSC Adv., 2019, 9, 12110 DOI: 10.1039/C9RA01356C

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