Enhanced Cancer Starvation Therapy Based on Glucose Oxidase/3-Methyladenine-Loaded Dendritic Mesoporous OrganoSilicon Nanoparticles.

Fan Wu,Hui Cheng,Yelin Wu,Jieyun Shi,Yun Meng,Yang Liu,Yang Chen

doi:10.3390/biom11091363

Abstract

Cell autophagy is a well-known phenomenon in cancer, which limits the efficacy of cancer therapy, especially cancer starvation therapy. Glucose oxidase (GOx), which is considered as an attractive starvation reagent for cancer therapy, can effectively catalyze the conversion of glucose into gluconic acid and hydrogen peroxide (H2O2) in the presence of O2. However, tumor cells adapt to survive by inducing autophagy, limiting the therapy effect. Therefore, anti-cell adaptation via autophagy inhibition could be used as a troubleshooting method to enhance tumor starvation therapy. Herein, we introduce an anti-cell adaptation strategy based on dendritic mesoporous organosilica nanoparticles (DMONs) loaded with GOx and 3-methyladenine (3-MA) (an autophagy inhibition agent) to yield DMON@GOx/3-MA. This formulation can inhibit cell adaptative autophagy after starvation therapy. Our in vitro and in vivo results demonstrate that autophagy inhibition enhances the efficacy of starvation therapy, leading to tumor growth suppression. This anti-cell adaptation strategy will provide a new way to enhance the efficacy of starvation cancer therapy.

Highlights

Deriving from an ancient concept of anti-angiogenesis, cancer starvation therapy implemented via ensuring an insufficient supply of nutrition and oxygen by obstructing blow vessels, has been proposed as a new antitumor approach [1,2]
The biodegradable dendritic mesoporous organosilica nanoparticles (DMONs) were synthesized via the hydrolysis of tetraethyl orthosilicate (TEOS) and 1,2-bis(triethoxysilyl)ethane (BTEE) with the assistance of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal)
The surface of DMON was functionalized by -NH2 groups for the further modification of glucose oxidase (GOx), as shown in Figure 2E, the zeta potential of DMON-NH2 turned negative (−30.4 mV) to positive (+19.7 mV) after the -NH2 functionalization

Summary

Introduction

Deriving from an ancient concept of anti-angiogenesis, cancer starvation therapy implemented via ensuring an insufficient supply of nutrition and oxygen by obstructing blow vessels, has been proposed as a new antitumor approach [1,2]. Glucose oxidase (GOx) can catalyze the oxidation of glucose to gluconic acid and hydrogen peroxide (H2 O2 ) in the presence of O2 , leading to the simultaneous consumption of oxygen and glucose, and starvation [9,10,11]. Cells under this metabolizing pressure of starvation and acidosis will activate autophagy, one of the cellular adaptative mechanisms, to prolong their survival

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Conclusion