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

• Published in: ACS applied materials & interfaces Vol. 10; no. 49; pp. 42115 - 42126
• Main Authors: Wu, Jianrong, Bremner, David H, Niu, Shiwei, Shi, Menghan, Wang, Haijun, Tang, Ranran, Zhu, Li-Min
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 12.12.2018
• Subjects: Animals; Cell Line, Tumor; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Humans; Hyperthermia, Induced; Indocyanine Green - chemistry; Indocyanine Green - pharmacokinetics; Indocyanine Green - pharmacology; Mice; Mice, Nude; Nanocapsules - chemistry; Nanocapsules - therapeutic use; Organosilicon Compounds - chemistry; Organosilicon Compounds - pharmacokinetics; Organosilicon Compounds - pharmacology; Phototherapy; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacokinetics; Polyethylene Glycols - pharmacology; nanotheranostics; biodegradability; low-temperature photothermal therapy; chemodrug gatekeeper; hollow mesoporous organosilica
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.8b16448

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 (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 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.