Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

Xiaoju Guo; Xiaoxiao Chen; Jiayi Ding; Feng Zhang; Shunyang Chen; Xin Hu; Shiji Fang; Lin Shen; Chenying Lu; Zhongwei Zhao; Jianfei Tu; Gaofeng Shu; Minjiang Chen; Jiansong Ji

Asian Journal of Pharmaceutical Sciences (Apr 2024)

Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

Xiaoju Guo,
Xiaoxiao Chen,
Jiayi Ding,
Feng Zhang,
Shunyang Chen,
Xin Hu,
Shiji Fang,
Lin Shen,
Chenying Lu,
Zhongwei Zhao,
Jianfei Tu,
Gaofeng Shu,
Minjiang Chen,
Jiansong Ji

Affiliations

Xiaoju Guo: Lishui Central Hospital, Shaoxing University, Shaoxing 312000, China; Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China
Xiaoxiao Chen: Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Key Laboratory of Precision Medicine of Lishui, Lishui 323000, China
Jiayi Ding: Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China
Feng Zhang: Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China
Shunyang Chen: Lishui Central Hospital, Shaoxing University, Shaoxing 312000, China; Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China
Xin Hu: Lishui Central Hospital, Shaoxing University, Shaoxing 312000, China; Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China
Shiji Fang: Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui 323000, China
Lin Shen: Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China
Chenying Lu: Lishui Central Hospital, Shaoxing University, Shaoxing 312000, China; Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui 323000, China; Key Laboratory of Precision Medicine of Lishui, Lishui 323000, China
Zhongwei Zhao: Lishui Central Hospital, Shaoxing University, Shaoxing 312000, China; Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui 323000, China; Key Laboratory of Precision Medicine of Lishui, Lishui 323000, China
Jianfei Tu: Lishui Central Hospital, Shaoxing University, Shaoxing 312000, China; Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui 323000, China; Key Laboratory of Precision Medicine of Lishui, Lishui 323000, China
Gaofeng Shu: Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Key Laboratory of Precision Medicine of Lishui, Lishui 323000, China; Corresponding authors.
Minjiang Chen: Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Key Laboratory of Precision Medicine of Lishui, Lishui 323000, China; Corresponding authors.
Jiansong Ji: Lishui Central Hospital, Shaoxing University, Shaoxing 312000, China; Zhejiang Key Laboratory of Imaging and Interventional Medicine, Imaging Diagnosis and Interventional Minimally Invasive Institute, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China; Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui 323000, China; Key Laboratory of Precision Medicine of Lishui, Lishui 323000, China; Corresponding authors.

Journal volume & issue: Vol. 19, no. 2
p. 100905

Abstract

Read online

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

Published in Asian Journal of Pharmaceutical Sciences

ISSN: 1818-0876 (Print)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.journals.elsevier.com/asian-journal-of-pharmaceutical-sciences/

About the journal

Abstract

Keywords