Intratumoral lactic acid neutralization strategy for boosting chemoimmunotherapy using liposomal sodium bicarbonate

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外文标题：Intratumoral lactic acid neutralization strategy for boosting chemoimmunotherapy using liposomal sodium bicarbonate

外文摘要：Glycolysis-related lactic acid overproduction creates an"ion-trapping"barrier and immunosuppressive tumor microenvironment that compromise effective intratumoral drug delivery and therapy.Therefore,normalization of tumor microenvironment via lactic acid neutralization can be a promising avenue for overcoming this therapeutic hurdle.In this study,the flexible liposomes loaded with sodium bicarbonate(NaHCO3@Flip)were used as a nano-adjuvant to boost chemoimmunotherapy.Their effects on assisting DOXIL and anti-programmed cell death protein 1(PD-1)therapy were investigated.NaHCO3@Flip achieved deep tumor penetration,with the ability to neutralize lactic acid and normalize the acidic tumor microenvironment.NaHCO3@Flip is biosafe and can enhance cellular uptake efficiency of doxorubicin(DOX)by overcoming the ion-trapping barrier and amplify immunogenic cell death induced by DOX.The combination therapy of liposomal DOX and NaHCO3@Flip demonstrated enhanced inhibition of tumor growth.NaHCO3@Flip can also synergize with PD-1 antibody therapy.NaHCO3@Flip has the potential to serve as a therapeutic adjuvant for boosting chemoimmunotherapy by overcoming the ion-trapping effect and normalizing the tumor microenvironment.

外文关键词：

Sodium bicarbonateLactic acid neutralizationTumor microenvironment normalizationChemoimmunotherapyPD-1 antibodyIon-trapping barrier

作者：

Taoxing Peng、Xinyue Shao、Wenqin Song、Weihua Xu、Wei Xiong、Yihao He、Yang Ding、Yongzhuo Huang

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作者单位：

State Key Laboratory of Natural Medicines,Department of Pharmaceutics,China Pharmaceutical University,Nanjing 210009,China

State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

University of Chinese Academy of Sciences,Beijing 100049,China

School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China

Zhongshan Institute for Drug Discovery,Shanghai Institutes of Materia Medica,Chinese Academy of Sciences,Zhongshan 528400,China

NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,Shanghai 201203,Ch

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关键词：

Sodium bicarbonate Lactic acid neutralization Tumor microenvironment normalization Chemoimmunotherapy PD-1 antibody Ion-trapping barrier

出版年：

2024

DOI：

10.1016/j.scib.2024.08.042

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

年,卷(期)：2024.69(24)