Chemodrug-gated biodegradable hollow mesoporous organosilica nanotheranostics for multimodal imaging-guided low-temperature photothermal therapy/chemotherapy of cancer

Noninvasive 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) nanoplatform 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 and shows a reduced risk for drug accumulation. After loading indocyanine green (ICG), the heat-shock protein 90 (Hsp 90) inhibitor, and 17AAG and modification with polyethylene glycol (NH ₂ -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 loading conferred 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 payload release and theranostic performance but also provides an outstanding low-temperature PTT strategy, which is highly valid in the 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.