Self-Delivery Photodynamic Nanoinhibitors for Tumor Targeted Therapy and Metastasis Inhibition.

Abstract

Simultaneous inhibitions of primary tumor growth and distant metastasis are very critical for cancer patients to improve their survival and cure rates. Although photodynamic therapy (PDT) shows great potential for primary tumor treatment, it often exacerbates hypoxia with a reduced therapeutic efficacy and subsequently contributes to carcinoma progression and metastatic dissemination. To solve these issues, self-delivery photodynamic nanoinhibitors (PNI) are developed for tumor targeted therapy and metastasis inhibition. PNI are composed of a carbonic anhydrase inhibitor (CAi), a hydrophilic poly(ethylene glycol) (PEG) linker, and a hydrophobic photosensitizer protoporphyrin IX (PpIX). Such self-delivery design of PNI avoids the premature release and heterogeneous distribution of CAi and PpIX to enhance the availability and synergism. Briefly, the CAi-based nanoinhibitors improve the selectivity of CAi for specific recognition and inhibition of tumor-associated isoform carbonic anhydrase (CA) IX, which would not only facilitate the targeted drug delivery of PNI but also regulate the hypoxia-induced signaling cascade and PDT resistance. Benefiting from the CA IX inhibition and targeted PDT, PNI exhibit a robust inhibitory effect on primary tumor growth and distant metastasis. This targeted self-delivery strategy sheds light on the photosensitizer-based molecular design to overcome the defect of traditional PDT.