Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy.
Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy.
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用混合纳米弹靶向缺氧肿瘤进行不依赖氧气的协同光热和热力学治疗
DOI：
10.1007/s40820-021-00616-4
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发表时间：
2021-03-31
影响因子：
26.6
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Gao D;Chen T;Chen S;Ren X;Han Y;Li Y;Wang Y;Guo X;Wang H;Chen X;Guo M;Zhang YS;Hong G;Zhang X;Tian Z;Yang Z
开发了标记为ZPA@HA-ACVA-AZ NB的全有机杂化纳米粒子，用于通过氧非依赖性协同PTT/TDT“精确打击“缺氧肿瘤，具有优于传统ROS介导的癌症治疗的治疗优势。通过表面修饰的HA（靶向CD 44受体）和AZ（靶向CA IX）的双重靶向作用，纳米球有效地在缺氧肿瘤处积聚。智能纳米球的协同作用可以通过AZ抑制CA IX和协同PTT/TDT来抑制原发性乳腺肿瘤生长和肺转移。在线版本包含补充材料，可通过10.1007/s40820-021-00616-4获得。缺氧是实体瘤的特征，并且它阻碍氧依赖性癌症治疗的治疗功效。在本文中，我们已经开发了全有机氧非依赖性杂化纳米粒子ZPA@HA-ACVA-AZ，用于通过表面修饰的透明质酸（HA）和缺氧依赖性因子碳酸酐酶IX（CA IX）抑制剂乙酰唑胺（AZ）的双重靶向作用来“精确打击”缺氧肿瘤。纳米颗粒的核心是特殊的酞菁锌聚集体（ZPA），其可以在808-nm激光照射下加热肿瘤组织用于光热治疗（PTT），沿着HA侧链上的烷基链官能化的可热分解自由基引发剂ACVA-HDA用于提供氧非依赖性烷基自由基用于通过热力学治疗（TDT）消融缺氧癌细胞。这些结果提供了重要的证据，证明反向缺氧标志CA IX作为AZ抑制的靶点和协同PTT/TDT的组合具有与传统（活性氧（ROS）介导的）癌症治疗相比不可比拟的治疗优势，用于抑制缺氧肿瘤的生长及其转移。 在线版本包含补充材料，可通过10.1007/s40820-021-00616-4获得。
An all-organic hybrid nanobullets labeled as ZPA@HA-ACVA-AZ NBs was developed for the “precise strike”of hypoxic tumors through an oxygen-independently synergistic PTT/TDT, possessing therapeutic advantages over traditional ROS-mediated cancer treatment. By feat of dual-targeting effect from surface-modified HA (targeting CD44 receptors) and AZ (targeting CA IX), the nanobullets accumulated at hypoxic tumors efficiently. The synergism of intelligent nanobullets could suppress the primary breast tumor growth and lung metastasis via CA IX inhibition by AZ and synergistic PTT/TDT. The online version contains supplementary material available at 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. The online version contains supplementary material available at 10.1007/s40820-021-00616-4.
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