Porphyrin-based porous organic polymer coated ZIF-8 nanoparticles as tumor targeted photosensitizer for combination cancer photodynamic/photothermal therapy

Abstract

The issue of low tumor-targeting and easy aggregation of small-molecule photosensitizers (PSs), as well as the heterogeneity and complexity of tumor tissue, greatly limit the therapeutic efficiency of phototherapy. Herein, a porphyrin-based organic polymer (POP) coated zeolitic imidazolate framework-8 (ZIF-8) hybrid nanoparticles (POP@ZIF-8) was developed, for delivering photosensitizer (porphyrin-based POP) specifically into tumor sites. The low-cost, biocompatible, tumor-specific POP@ZIF-8 with core-shell structure was prepared via a simple but efficient covalent surface-coating strategy, in which the pH-responsive ZIF-8 functioned as templates, finely controlling the nanometer size of the hybrid and ensuring targeted delivery of PSs to tumor tissue. Moreover, a direct covalently coated polymer-based PSs on ZIF-8 can better preserve optical properties compared to conventional physical adsorption methods. Under laser irradiation, the resulting hybridization not only efficiently converts light into local heat, causing severe photothermal damage to tumor tissue, but also synergistically promotes the production of strongly toxic 1O2, which exerts a photodynamic treatment on tumor sites. Therefore, this special POP@ZIF-8 hybrid presented a cooperatively enhanced synergistic photodynamic/photothermal anticancer efficacy, as demonstrated both the in vitro and in vivo assay, systematically. This study presents a practicable and reliable strategy to develop stable and high-efficiency cancer phototherapy agents which could simultaneously manipulate the structural characteristics and performance of targeted materials for promising noninvasive multi-mode anti-cancer.