Selenium-Rich Polymeric Nanophotosensitizers for Enhanced Tumor Photodynamic Therapy through Intermolecular Heavy Atom Effect

The incorporation of heavy atoms into chromophores is a prevalent strategy employed to enhance the ROS generation of photosensitizers (PSs). However, this approach often necessitates extensive modifications, leading to complex synthesis processes and reduced water solubility of PSs. Herein, we present a series of polymeric nanophotosensitizers (PolyC NPs, PolyS NPs, and PolySe NPs) to evaluate the impact of intermolecular heavy atom effects (HAE) on photosensitivity enhancement of PSs. The energy gap (Δ<i>E</i>_S-T) between the first excited singlet (S₁) and triplet (T₁) states of PPa in PolySe NPs is reduced by 0.349 eV compared to PolyC NPs. Therefore, PolySe NPs exhibit approximately 1.5-fold increase in ROS generation and 1.4-fold greater phototoxicity against 4T1 cancer cell lines in vitro. Moreover, PolySe NPs exhibit the most pronounced tumor inhibition effects in vivo. This study first explores the application of intermolecular HAE to advance the efficacy of antitumor photodynamic therapy.