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Research Article | Online first | Published: 27 February 2023

Hybrid transcytosis nanopomegranates for sensitizing breast cancer radiotherapy in deep tumor tissue

Show Author's Information Li Wang2,§,  Liang Xiao4,§,  Zhengyang Zhao4,§,  Kai Zhong4,  Weiliang Zhu1( ),  Hao Liu3( ),  Xiaoqiu Li1( )
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, China
Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

§ Li Wang, Liang Xiao, and Zhengyang Zhao contributed equally to this work.

Keywords:
breast cancer, transcytosis, hybrid nanopomegranate, hypoxia alleviation, radiosensitization
Subject:
  theranostics
Cite this article:
Wang L, Xiao L, Zhao Z, et al. Hybrid transcytosis nanopomegranates for sensitizing breast cancer radiotherapy in deep tumor tissue. Nano Research, 2023, https://doi.org/10.1007/s12274-023-5375-2
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Abstract Full text Electronic supplementary material About this article

As a standard cancer treatment method, radiotherapy (RT) has cured or alleviated over half cancer bearing patients worldwide more than 100 years. However, the therapeutic outcome is seriously hindered by the resistant tumor microenvironment (TME). Hypoxia is a critical factor of vicious TME that causes radiation resistance owing to the insufficiency of oxygen for DNA damage maintenance. Moreover, severe vascular dysfunction and pyknomorphic extracellular matrix (ECM) in deep tumor tissues substantially limit radiosensitizer penetration and oxygen diffusion from vessels into tightly packed tumor core. In this study, we develop a hybrid transcytosis nanopomegranate (HTP) with high transcytosis potential in response to TME condition. HTP is architected by self-assembly of small CuS and Au nanoparticles (NPs) at normal physiological condition. HTP can rapidly collapse to transcytosis NPs (CuS and Au NPs) in TME with cationized surface, which enables excellent transcytosis potential and effectively elevates the penetration of CuS and Au into deep tumor tissues. Following the second near-infrared (NIR(II)) biowindow laser irradiation, CuS heats the tumor and enhances blood perfusion, eliciting tumor hypoxia alleviation and DNA damage aggravation. Moreover, Au NPs enriched in deep tumor tissues effectively sensitize radio-therapeutic response. Our study provides a new and potential nano-platform to ameliorate tumor hypoxia and sensitize deep tumor tissue radiotherapy.


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Abstract
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Electronic supplementary material
About this article

Hybrid transcytosis nanopomegranates for sensitizing breast cancer radiotherapy in deep tumor tissue

Show Author's information Li Wang2,§, Liang Xiao4,§, Zhengyang Zhao4,§, Kai Zhong4, Weiliang Zhu1( ), Hao Liu3( ), Xiaoqiu Li1( )
Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai 519000, China
Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

§ Li Wang, Liang Xiao, and Zhengyang Zhao contributed equally to this work.

Abstract

As a standard cancer treatment method, radiotherapy (RT) has cured or alleviated over half cancer bearing patients worldwide more than 100 years. However, the therapeutic outcome is seriously hindered by the resistant tumor microenvironment (TME). Hypoxia is a critical factor of vicious TME that causes radiation resistance owing to the insufficiency of oxygen for DNA damage maintenance. Moreover, severe vascular dysfunction and pyknomorphic extracellular matrix (ECM) in deep tumor tissues substantially limit radiosensitizer penetration and oxygen diffusion from vessels into tightly packed tumor core. In this study, we develop a hybrid transcytosis nanopomegranate (HTP) with high transcytosis potential in response to TME condition. HTP is architected by self-assembly of small CuS and Au nanoparticles (NPs) at normal physiological condition. HTP can rapidly collapse to transcytosis NPs (CuS and Au NPs) in TME with cationized surface, which enables excellent transcytosis potential and effectively elevates the penetration of CuS and Au into deep tumor tissues. Following the second near-infrared (NIR(II)) biowindow laser irradiation, CuS heats the tumor and enhances blood perfusion, eliciting tumor hypoxia alleviation and DNA damage aggravation. Moreover, Au NPs enriched in deep tumor tissues effectively sensitize radio-therapeutic response. Our study provides a new and potential nano-platform to ameliorate tumor hypoxia and sensitize deep tumor tissue radiotherapy.

Keywords: breast cancer, transcytosis, hybrid nanopomegranate, hypoxia alleviation, radiosensitization

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Publication history

Received: 10 August 2022
Revised: 30 November 2022
Accepted: 03 December 2022
Published: 27 February 2023

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© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 32101139 and 81901888), the Fundamental Research Fund for the Central Universities (No. WK9100000006), the China Postdoctoral Science Foundation (No. 2020M683160), the Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515220028), and the Natural Science Foundation of Anhui Province of China (No. 1908085MH247). All animals received were in compliance with the guidelines outlined in the Guide for the Care and Use of Laboratory Animals, and all procedures were approved by the University of Science and Technology of China Animal Care and Use Committee (No. USTCACUC1801062).

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