Journal
NANO-MICRO LETTERS
Volume 13, Issue 1, Pages -Publisher
SHANGHAI JIAO TONG UNIV PRESS
DOI: 10.1007/s40820-021-00616-4
Keywords
Photothermal therapy (PTT); Thermodynamic therapy (TDT); Targeting hybrid nanobullet; Hypoxia tumor; Zinc phthalocyanine aggregate (ZPA)
Funding
- National Natural Science Foundation of China [51903203, 51703178, 81770728]
- China Postdoctoral Science Foundation [2019M653661, 2019M663742]
- Natural Science Foundation of Shaanxi Province [2020JQ-046]
- Natural Science Foundation of Zhejiang Province [LWY20H180002]
- Natural Science Foundation of Guangxi Zhuang Autonomous Region [2017GXNSFBA198028]
- MIT, Harvard
- Stanford University
- Brigham Research Institute
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The development of all-organic oxygen-independent hybrid nanobullets, utilizing surface-modified hyaluronic acid and hypoxia-dependent factors for precise targeting of hypoxic tumors, provides significant therapeutic advantages in suppressing the growth of hypoxic tumors and their metastasis.
Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment. Herein, we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the precise strike of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid (HA) and hypoxia-dependent factor carbonic anhydrase IX (CA IX)-inhibitor acetazolamide (AZ). The core of nanobullets is the special zinc (II) phthalocyanine aggregates (ZPA) which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy (PTT), along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy (TDT). The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional (reactive oxygen species (ROS)-mediated) cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.
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