Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 38, Pages 34755-34765Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b12879
Keywords
Janus gold triangle-mesoporous silica; liver cancer; hypoxia-activated chemotherapy; radiosensitization; photothermal therapy
Funding
- National Key R&D Program of China [2017YFF0108600, 2017YFC0211900, 2016YFF0103800]
- National Natural Science Foundation of China [81771982, 81601609, 61535010, 8160071152, 21803075]
- Key Research Program of the Chinese Academy of Sciences [KFZDSW-210]
- Natural Science Foundation of Jiangsu Province [BE2015601, BK20181236]
- Science and Technology Department of Suzhou City [SS201539, SYG201724, ZXY201434]
- Developing Plan of Suzhou City [SZS201721]
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Radiation dosage constraints and hypoxia-associated resistance lead to the failure of radiotherapy (RT), especially in hypoxic liver cancer. Therefore, the intricate use of combined strategies for potentiating and complementing RT is especially important. In this work, we fabricated multifunctional Janus-structured gold triangle-mesoporous silica nanoparticles (NPs) as multifunctional platforms to deliver the hypoxia-activated prodrug tirapazamine (TPZ) for extrinsic radiosensitization, local photothermal therapy, and hypoxia-specific chemotherapy. The subsequent conjugation of folic acid-linked poly(ethylene glycol) provided the Janus nanoplatforms with liver cancer targeting and minimized opsonization properties. In vitro and in vivo experiments revealed the combined radiosensitive and photothermal antitumor effects of the Janus nanoplatforms. Importantly, the TPZ-loaded Janus nanoplatforms exhibited pH-responsive release behavior, which effectively improved the cellular internalization and therapeutic efficiency in hypoxic rather than normoxic liver cancer cells. Hypoxiaspecific chemotherapy supplemented the ineffectiveness of radio-photothermal therapy in hypoxic tumor tissues, resulting in remarkable tumor growth inhibition without systematic toxicity. Therefore, our Janus nanoplatforms integrated radio-chemophotothermal therapy in a hypoxia-activated manner, providing an efficient and safe strategy for treating liver cancer.
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