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

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

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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.

CaCO3-based nanoparticlesHypoxia attenuationAcidity neutralizationReversal of chemotherapyresistanceEnhanced 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

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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

Key Laboratory of Precision Medicine of Lishui,Lishui 323000,China

Clinical College of The Affiliated Central Hospital,School of Medicine,Lishui University,Lishui 323000,China

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Key R&D Program of Lishui CityKey R&D Program of Lishui CityKey R&D Program of Lishui CityNatural Science Foundation of ChinaNatural Science Foundation of ChinaNatural Science Foundation of ChinaZhejiang Provincial Natural Science FoundationZhejiang Provincial Natural Science FoundationProvincial and Ministerial Joint Construction of Key Projects

2021ZDYF122022ZDYF072023zdyf14820720268207202582272090LY23H180003LQ22H180010WKJ-ZJ-2317

2024

10.1016/j.ajps.2024.100905

亚洲药物制剂科学(英文版)
沈阳药科大学

亚洲药物制剂科学(英文版)

ISSN：1818-0876
年,卷(期)：2024.19(2)