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Reversing tumor fibrosis for potentiating chemo-immunotherapy via lactic acid exhaustion by codelivery of bicarbonate and JQ1

文献类型：期刊论文

作者Peng, Taoxing5,6; He, Yihao5; Shao, Xinyue4,5; Liu, Han4,5; Yang, Lu3,5; Xiong, Wei2; Jin, Xiaoying5; Ding, Yang6; Huang, Yongzhuo1,2,3,4,5
刊名NANO TODAY
出版日期2025-04-01
卷号61页码:16
关键词sodium bicarbonate Nano-adjuvant Lactic acid exhaustion Tumor fibrosis reversal Chemo-immunotherapy
ISSN号1748-0132
DOI10.1016/j.nantod.2025.102657
英文摘要Tumor fibrosis imposes a formidable barrier against effective chemo-immunotherapy, typically resulting in limited infiltration of immune cells and poor drug penetration into the tumor. In this study, it was revealed that intratumoral lactic acid exhaustion can relieve tumor fibrosis by suppressing TGF-(3 pathway. The bicarbonate liposomes loaded with JQ1 (JQ1/NaHCO3@TLip) was constructed, with surface modification with lactoferrin (LF) that enabled tumor-targeting delivery via binding with LRP-1 receptors. Intratumoral lactic acid can be reduced via both neutralization and epigenetic-metabolism regulation. JQ1/NaHCO3@TLip was demonstrated to effectively reverse tumor fibrosis, thereby promoting immune cell infiltration, and enhancing deep penetration of both nanomedicine (e.g., liposomal doxorubicin (DOX@Lip)) and protein drugs (e.g., anti-PD-1). Importantly, the combination of low-dose DOX@Lip and JQ1/NaHCO3@TLip exhibited remarkable efficacy with reducing side toxicity. This combination approach also effectively inhibited tumor recurrence and distant metastasis. Moreover, pretreatment with JQ1/NaHCO3@TLip showed a synergistic effect on enhancing tumor inhibition efficacy of anti-PD-1 therapy. These findings indicate that JQ1/NaHCO3@TLip is promising as a nano-adjuvant to enhance chemo-immunotherapy via lactic acid exhaustion.
WOS关键词PH ; MICROENVIRONMENT ; LACTATE ; MATRIX ; CELLS ; BETA
资助项目National Key Research and Development Program of China[2022YFE0203600] ; National Natural Science Foundation of China[81925035] ; National Natural Science Foundation of China[82341232] ; International Partnership Program of the Chinese Academy of Sciences[083GJHZ2023021GC] ; International Partnership Program of the Chinese Academy of Sciences[083GJHZ2023012FN] ; Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute)[2021B0909050003] ; Chinese Academy of Sciences President's International Fellowship Initiative[2024VBB0004] ; Scientific Innovation Group Project in Zhongshan[CXTD2022011]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001424178000001
出版者ELSEVIER SCI LTD
源URL[http://119.78.100.183/handle/2S10ELR8/316272]  
专题新药研究国家重点实验室
通讯作者Ding, Yang; Huang, Yongzhuo
作者单位1.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.China Pharmaceut Univ, Dept Pharmaceut, State Key Lab Nat Med, Nanjing 210009, Peoples R China
推荐引用方式
GB/T 7714		 Peng, Taoxing,He, Yihao,Shao, Xinyue,et al. Reversing tumor fibrosis for potentiating chemo-immunotherapy via lactic acid exhaustion by codelivery of bicarbonate and JQ1[J]. NANO TODAY,2025,61:16.
APA Peng, Taoxing.,He, Yihao.,Shao, Xinyue.,Liu, Han.,Yang, Lu.,...&Huang, Yongzhuo.(2025).Reversing tumor fibrosis for potentiating chemo-immunotherapy via lactic acid exhaustion by codelivery of bicarbonate and JQ1.NANO TODAY,61,16.
MLA Peng, Taoxing,et al."Reversing tumor fibrosis for potentiating chemo-immunotherapy via lactic acid exhaustion by codelivery of bicarbonate and JQ1".NANO TODAY 61(2025):16.

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来源：上海药物研究所

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