Gao Di, Chen Ting, Chen Shuojia, Ren Xuechun, Han Yulong, Li Yiwei, Wang Ying, Guo Xiaoqing, Wang Hao, Chen Xing, Guo Ming, Zhang Yu Shrike, Hong Guosong, Zhang Xingcai, Tian Zhongmin, Yang Zhe
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, People's Republic of China.
Paulson School of Engineering and Applied Sciences, John A, Harvard University, Cambridge, MA, 02138, USA.
Nanomicro Lett. 2021 Mar 31;13(1):99. doi: 10.1007/s40820-021-00616-4.
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.
缺氧是实体瘤的一个特征，它会阻碍依赖氧气的癌症治疗的疗效。在此，我们开发了全有机非氧依赖型混合纳米子弹ZPA@HA-ACVA-AZ，通过表面修饰的透明质酸（HA）和缺氧依赖因子碳酸酐酶IX（CA IX）抑制剂乙酰唑胺（AZ）的双重靶向作用，对缺氧肿瘤进行“精确打击”。纳米子弹的核心是特殊的锌（II）酞菁聚集体（ZPA），其在808纳米激光照射下可加热肿瘤组织以进行光热疗法（PTT），同时HA侧链上的烷基链功能化热分解自由基引发剂ACVA-HDA可提供非氧依赖型烷基自由基，通过热动力学疗法（TDT）消融缺氧癌细胞。结果提供了重要证据，表明以CA IX作为反向缺氧标志物并通过AZ进行抑制，以及协同PTT/TDT相结合，在抑制缺氧肿瘤生长及其转移方面，比传统的（活性氧（ROS）介导的）癌症治疗具有无可比拟的治疗优势。
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