Multi-Path Tumor Inhibition via the Interactive Effects between a Tumor Microenvironment and an Oxygen Self-Supplying Delivery System for a Photosensitizer

Multi-Path Tumor Inhibition via the Interactive Effects between a Tumor Microenvironment and an Oxygen Self-Supplying Delivery System for a Photosensitizer:

Publication date: Available online 30 December 2019

Source: Photodiagnosis and Photodynamic Therapy

Author(s): Xue Rui, Ye Yang, Jingjing Wu, Jing Chen, Qingqing Chen, Rongrong Ren, Qingqing Zhang, Yingying Hu, Dengke Yin

Abstract

The tumor microenvironment (TME) affects not only tumor growth and metastasis, but also therapy efficacy. In the present study, an oxygen self-supplying delivery system for a photosensitizer (O₂-PDS), with an oxygen source of calcium peroxide (CPO), has been designed to induce multi-path tumor apoptosis through interactive effects with the TME. In anti-tumor experiments, the CPO decomposition and O₂ released from the O₂-PDS are site-activated and accelerated by high interstitial pressure and low pH level of the TME. The CPO decomposition products of O₂ and Ca²⁺ lead to direct tumor apoptosis by irradiation generated singlet oxygen and mitochondrial calcium overload. The decomposition products of OH- and O₂ relieves the acid and hypoxic state of TME, inducing a decrease in tumor proliferation and metastasis. This multi-path tumor apoptosis leads to a positive therapeutic effect on an animal tumor model and nontoxicity in normal tissue.

Graphical abstract

A simple oxygen self-supplying delivery system for photosensitizer is developed to achieve multi-path tumor inhibition through site-activated mitochondria calcium overload, singlet oxygen cytotoxicity, and microenvironment regulation in tumor tissues.