Nanostructured Organosilica Nitric Oxide Donors Intrinsically Regulate Macrophage Polarization with Antitumor Effect
Shevanuja Theivendran, Zhengying Gu, Jie Tang, Yannan Yang, Hao Song, Yang Yang, Min Zhang, Dan Cheng, Chengzhong Yu
Abstract
Nitric oxide (NO) has many important biological functions; however, it has been a long-standing challenge to utilize the exogenous NO donor itself in the activation of macrophages for cancer immunotherapy. Herein, we report the synthesis of a nanoparticle-based NO delivery platform with a rational design for effective NO delivery and macrophage activation. S-Nitrosothiol (SNO) modified organosilica nanoparticles with a tetrasulfide-containing composition produced a higher level of intracellular NO than their bare silica counterparts in macrophages. Enhanced intracellular delivery of NO resulted in mitochondrial dysfunction and disruption of the tricarboxylic acid cycle, leading to macrophage activation and delayed tumor growth. This study provides insights on intracellularly delivered NO for regulating the polarization of macrophages and cancer immunotherapy.