Biodegradable iron-doped ZIF-8 based nanotherapeutic system with synergistic chemodynamic/photothermal/chemo-therapy

Developing nanotherapeutic system with combined antitumor capability has increasingly become a promising strategy for cancer treatment. Herein, we present a biodegradable iron-doped ZIF-8 based nanoconstruct to integrate merits of chemodynamic therapy, photothermal therapy and chemotherapy into "all-in-one'' nanoplatform. Specifically, the nanoconstruct is assembled by loading chemotherapeutic drug (doxorubicin, DOX) and photothermal transforming agent (indocyanine green, ICG) into Fe2+-doped ZIF-8 nanocrystals. Benefiting from the intrinsic pH-responsive property, the ZIF-8 nanoconstruct can be degraded easily in the typically acidic tumor microenvironment or cancer cells, leading to smart tumor microenvironment-responsive Fe2+, DOX and ICG release at high-rate. Particularly, the ZIF-8 nanoconstruct can release Fe2+ rather than Fe3+ of lower Fenton catalytic activity, leading to efficient Fenton reaction to generate abundant hydroxyl radical (center dot OH) for chemodynamic therapy. The released DOX and ICG demonstrate exceptional chemotherapy and near infrared laser triggered photothermal therapy capability with high photothermal conversion efficiency (35.9%), respectively. In turn, the photothermal therapy can significantly enhance the chemodynamic therapy effect. The as-designed nanoconstruct with synergistic therapeutic efficacy provide a fatality rate as high as 93.7% for cancer cells, which is promising for efficient cancer eradication.