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Precise clinical treatment of triple-negative breast cancer (TNBC) is an obstacle in clinic. Nanotechnology-assisted photothermal therapy (PTT) is a superior treatment modality for TNBC in terms of precision. However, thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of PTT. AT13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study, showing satisfactory antitumour activity through molecularly targeted therapy (MTT). Whereas, it has poor solubility. Hence hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds, forming an amphipathic copolymer that could self-assembled into nanomicelles, followed by encapsulating Cypate and AT13387. These nanomicelles exhibited great features, including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs, increasing the solubility of Cypate and AT13387, showing a pH/redox dual response that contributes to drug release, and having the ability of active targeting. Thus, the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.


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Hyaluronic acid-based dual-responsive nanomicelles mediated mutually synergistic photothermal and molecular targeting therapies

Show Author's information Liangliang Cai1,§Ronghua Ni1,§Xiaofei Ma1,§Rongrong Huang1Zhiyuan Tang1Jinqiu Xu1Yong Han2( )Yuehua Guo3( )Zhifeng Gu4( )
Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong 226001, China
Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong 226001, China

§ Liangliang Cai, Ronghua Ni, and Xiaofei Ma contributed equally to this work.

Abstract

Precise clinical treatment of triple-negative breast cancer (TNBC) is an obstacle in clinic. Nanotechnology-assisted photothermal therapy (PTT) is a superior treatment modality for TNBC in terms of precision. However, thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of PTT. AT13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study, showing satisfactory antitumour activity through molecularly targeted therapy (MTT). Whereas, it has poor solubility. Hence hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds, forming an amphipathic copolymer that could self-assembled into nanomicelles, followed by encapsulating Cypate and AT13387. These nanomicelles exhibited great features, including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs, increasing the solubility of Cypate and AT13387, showing a pH/redox dual response that contributes to drug release, and having the ability of active targeting. Thus, the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.

Keywords: hyaluronic acid, photothermal therapy, nanomicelles, dual responsive, molecular targeting therapy

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Publication history
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Acknowledgements

Publication history

Received: 12 February 2022
Revised: 25 March 2022
Accepted: 28 March 2022
Published: 07 May 2022
Issue date: July 2022

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© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 81900528), the China Postdoctoral Science Foundation (Nos. 2019M661908 and 2018M642297), the Postdoctoral Science Foundation of Jiangsu Province (No. 2020Z435), and the Science and technology Program of Nantong City (No. JC2021150).

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