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Vol. 13 (2021)

Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy

https://doi.org/10.1007/s40820-021-00616-4
Di Gao
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
Ting Chen
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
Shuojia Chen
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
Xuechun Ren
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
Yulong Han
Paulson School of Engineering and Applied Sciences, John A, Harvard University, Cambridge, MA 02138, USA
Yiwei Li
Paulson School of Engineering and Applied Sciences, John A, Harvard University, Cambridge, MA 02138, USA
Ying Wang
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
Xiaoqing Guo
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
Hao Wang
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
Xing Chen
School of Public Health, Guangxi Medical University, Nanning 530000, People’s Republic of China
Ming Guo
School of Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Yu Shrike Zhang
Division of Engineering in Medicine, Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, Cambridge, MA 02139, USA
Guosong Hong
Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA
Xingcai Zhang
Paulson School of Engineering and Applied Sciences, John A, Harvard University, Cambridge, MA 02138, USA
Zhongmin Tian
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
Zhe Yang
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

Corresponding Author: Zhe Yang

yangzhe@xjtu.edu.cn

Nano-Micro Letters, Vol. 13 (2021), Article Number: 99

Abstract

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.


Highlights:


1 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.
2 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.
3 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.

Keywords

Photothermal therapy (PTT) Thermodynamic therapy (TDT) Targeting hybrid nanobullet Hypoxia tumor Zinc phthalocyanine aggregate (ZPA)
Gao, Di, Ting Chen, Shuojia Chen, Xuechun Ren, Yulong Han, Yiwei Li, Ying Wang, Xiaoqing Guo, Hao Wang, Xing Chen, Ming Guo, Yu Shrike Zhang, Guosong Hong, Xingcai Zhang, Zhongmin Tian, and Zhe Yang. 2021. “Targeting Hypoxic Tumors With Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy”. Nano-Micro Letters 13 (March):99. https://doi.org/10.1007/s40820-021-00616-4.
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