Chemodrug-Gated Biodegradable Hollow Mesoporous Organosilica Nanotheranostics for Multimodal Imaging-Guided Low-Temperature Photothermal Therapy/Chemotherapy of Cancer

摘要： Non-invasive physical treatment with relatively low intensity stimulation and the development of highly efficient anticancer medical strategy are still desirable for cancer therapy. Herein, a versatile biodegradable hollow mesoporous organosilica nanocapsule (HMONs) nananoplatform that is capped by the gemcitabine (Gem) molecule through a pH-sensitive acetal covalent bond is designed. The fabricated nanocapsule exhibits desirable small molecule release at the tumor tissues/cell sites, shows a reduced potential for drug accumulation risk. After loading indocyanine green (ICG), the heat-shock protein 90 (Hsp 90) inhibitor, 17AAG and modification with polyethylene glycol (NH2-PEG), the resulting ICG-17AAG@HMONs-Gem-PEG exhibited a precisely controlled release of ICG and 17AAG and low-temperature photothermal therapy (PTT) (~41 °C) with excellent tumor destruction efficacy. In addition, ICG loaded conferring the nanoplatform with near-infrared fluorescence imaging (FL) and photoaccoustic (PA) imaging capability. In short, this work not only presents a smart drug self-controlled nanoplatform with pH-responsive payloads released and theranostic performance, but also provides an outstanding low-temperature PTT strategy, which is highly valid in inhibition of cancer cells with minimal damage to the organism. Therefore, this research provides a paradigm that has a chemodrug-gated HMONs-based theranostic nanoplatform with intrinsic biodegradability, multimodal imaging capacity, high low-temperature PTT/chemotherapy efficacy and reduced systemic toxicity.