Abstract

The heterogeneity of tumor microenvironment leads to uneven distribution of bio-stimuli. Thus, the multi-site delivery efficiency of responsive drug delivery systems (DDS) inner tumor was always limited. Herein, we proposed a combination strategy of photodynamic therapy (PDT) with ROS-responsive nanosystem which was constructed from dextran-phenylboronic acid pinacol ester conjugates. This combination utilized PDT to amplify and homogenize tissular oxidation level, and achieve effective multi-site response and release of multi-target drugs like gambogic acid (GA). Our research demonstrated the successful preparation of GA and protoporphyrin IX (PpIX) co-loaded nanoparticles, and the PDT-mediated spatiotemporal controlled multi-site drug release in simulated conditions. Furthermore, data from in vitro and in vivo researches on B16F10 cells, HUVEC, and B16F10-bearing C57BL/6 mice potently confirmed the enhanced multi-mechanism regulations of GA mediated by the effective and homogeneous tumoral release. This tactic based on bio-stimuli amplification and homogenization proposes a paradigm to maximize the potency of multi-target drugs.