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

Taoxing Peng ¹Xinyue Shao ²Wenqin Song ³Weihua Xu ⁴Wei Xiong ⁵Yihao He ⁴Yang Ding ⁶Yongzhuo Huang⁷

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作者信息

1. 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
2. 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
3. School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China
4. State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China
5. Zhongshan Institute for Drug Discovery,Shanghai Institutes of Materia Medica,Chinese Academy of Sciences,Zhongshan 528400,China
6. State Key Laboratory of Natural Medicines,Department of Pharmaceutics,China Pharmaceutical University,Nanjing 210009,China
7. 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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Abstract

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.

Key words

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

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出版年

2024

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

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