Tumor Cell Distinguishable Nanomedicine Integrating Chemotherapeutic Sensitization and Protection

Sen Liu,Zhongmei Yang,Yong Hu,Li Quan,Wei Ye,Yanchun Wei,Can Shen,Changjiang Pan,Jianquan Wang,Cheng Qian

doi:10.3389/fbioe.2021.773021

Sen Liu, Zhongmei Yang + Show 8 more

Open Access

https://doi.org/10.3389/fbioe.2021.773021

Copy DOI

Abstract

Theoretically, with a high enough drug dosage, cancer cells could be eliminated. However, the dosages that can be administered are limited by the therapeutic efficacy and side effects of the given drug. Herein, a nanomedicine integrating chemotherapeutic sensitization and protection was developed to relieve the limitation of administration dosage and to improve the efficacy of chemotherapy. The nanomedicine was endowed with the function of synergistically controlled release of CO and drugs under near-infrared (NIR) light irradiation. CO photo-induced release system (COPIRS) was synthesized by constructing an electron excitation–electron transfer group–electron-induced CO release structure and was used as the hydrophobic part, and then hydrophilic polymer (polyethylene glycol; PEG) was introduced by a thermal-responsive groups (DA group), forming a near-infrared-induced burst-release nanocarrier. In vitro and in vivo experiments showed that the nanomedicine can distinguish between tumor and normal cells and regulates the resistance of these different cells through the controlled release of carbonic oxide (CO), simultaneously enhancing the efficacy of chemotherapy drugs on tumor cells and chemotherapeutic protection on normal cells. This strategy could solve the current limitations on dosages due to toxicity and provide a solution for tumor cure by chemotherapy.

Highlights

Chemotherapy is a widely used cancer treatment that could theoretically cure tumors provided that a sufficiently high drug dose is administered (Fung and Travis, 2018)
The combination of Chemotherapeutic sensitization (CS) and chemotherapeutic protection (CP) could reduce the dose required for cure by enhancing the efficacy of drugs on tumors but could increase the maximum-tolerated dose (MTD) by protecting normal cells from the toxicity of drugs, which might be an effective strategy to break through the limits of MTD on the effect of chemotherapy
The peak at 1740 cm−1 assigned to the C O stretching vibration of amide bond in carbonic oxide (CO) photo-induced release system (COPIRS) appeared

Summary

INTRODUCTION

Chemotherapy is a widely used cancer treatment that could theoretically cure tumors provided that a sufficiently high drug dose is administered (Fung and Travis, 2018). Synthesis of COPIRS-DA-PEG mPEG-DA was prepared by the Dies–Alder reaction, wherein 2.0 g of mPEG-Mal were dissolved in DMF and 1.1 ml of furfurylamine were added, stirred at room temperature in an N2 atmosphere for 48 h, and purified by dialysis and lyophilization. Temperature variation profiles of the COPIRS were obtained by measuring the change in temperature of a water and CO&Dox@NPs solution (1 mg/ml) exposed to laser irradiation (808 nm, 0.78 W/cm). When cells proliferated to ∼80–85% of confluence in every well, 100 μl of the medium containing different samples was added to each well: (1) IR3BPY2-DA-PEG@NPs, (2) Dox@NPs, (3) CO@NPs, (4) CO&Dox@NPs, and (5) CO&Dox@NPs. Groups 3 and 5 were irradiated by 808 nm laser for 10 min at 6 h post the incubation. Blood was collected in sodium EDTA anticoagulant tubes and analyzed

RESULTS AND DISCUSSION

DATA AVAILABILITY STATEMENT

ETHICS STATEMENT