Multi-path tumor inhibition via the interactive effects between tumor microenvironment and an oxygen self-supplying delivery system for a photosensitizer.

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.