Pillar[5]arene-based supramolecular nano-photosensitizer enhances cancer therapeutic effectiveness by generating multiple hypertoxic reactive species

Abstract

Damaging crucial molecular elements and structures, including lipids, proteins, and DNA within cancer cells, hypertoxic reactive species are capable of initiating the cell death process. However, single-reactive-specie-based therapeutic strategies frequently have poor effectiveness in damaging cancer cells due to cancer cells adapt or develop defence mechanisms to mitigate damage caused by oxidative stress. Developing therapeutic strategies that can produce multiple hypertoxic reactive species simultaneously is significant for improving cancer therapeutic effectiveness. Herein, a novel supramolecular photosensitizer WP5⊃NA was constructed based on the host-guest interactions between carboxylated pillar[5]arene (WP5) and L-arginine-functionalized benzophenothiazine (NA). The experimental results showed that WP5⊃NA NPs could efficiently reduce the uptake of NA by normal cells. This supramolecular photosensitizer can produce multiple hypertoxic reactive species in cancer cells through type I PDT and a series of oxidative reactions after exposure to 660 nm light, which can directly damage cancer cells and cause cancer cell apoptosis. This present study provides a novel strategy for enhanced cancer therapeutic effectiveness by supramolecular photosensitizers with the ability of generating multiple hypertoxic reactive species.