Relief of tumor hypoxia using a nanoenzyme amplifies NIR-II photoacoustic-guided photothermal therapy

Author:

Xue Qiang1,Zeng Silue2,Ren Yaguang,Pan Yingying3,Chen Jianhai,Chen Ningbo4ORCID,Wong Kenneth K. Y.4ORCID,Song Liang,Fang Chihua2,Guo Jinhan1,Xu Jinfeng1,Liu ChengboORCID,Zeng Jie3,Sun Litao5,Zhang Hai1,Chen JingqinORCID

Affiliation:

1. The First Affiliated Hospital of Southern University of Science and Technology

2. Southern Medical University

3. Third Affiliated Hospital of Sun Yat-Sen University

4. The University of Hong Kong

5. Affiliated People’s Hospital of Hangzhou Medical College

Abstract

Hypoxia is a critical tumor microenvironment (TME) component. It significantly impacts tumor growth and metastasis and is known to be a major obstacle for cancer therapy. Integrating hypoxia modulation with imaging-based monitoring represents a promising strategy that holds the potential for enhancing tumor theranostics. Herein, a kind of nanoenzyme Prussian blue (PB) is synthesized as a metal-organic framework (MOF) to load the second near-infrared (NIR-II) small molecule dye IR1061, which could catalyze hydrogen peroxide to produce oxygen and provide a photothermal conversion element for photoacoustic imaging (PAI) and photothermal therapy (PTT). To enhance stability and biocompatibility, silica was used as a coating for an integrated nanoplatform (SPI). SPI was found to relieve the hypoxic nature of the TME effectively, thus suppressing tumor cell migration and downregulating the expression of heat shock protein 70 (HSP70), both of which led to an amplified NIR-II PTT effect in vitro and in vivo, guided by the NIR-II PAI. Furthermore, label-free multi-spectral PAI permitted the real-time evaluation of SPI as a putative tumor treatment. A clinical histological analysis confirmed the amplified treatment effect. Hence, SPI combined with PAI could offer a new approach for tumor diagnosing, treating, and monitoring.

Funder

Basic and Applied Basic Research Foundation of Guangdong Province

Shenzhen Science and Technology Innovation Program

National Natural Science Foundation of China

National Key Research and Development Program of China

Publisher

Optica Publishing Group

Subject

Atomic and Molecular Physics, and Optics,Biotechnology

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