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Co-delivering irinotecan and imiquimod by pH-responsive micelle amplifies anti-tumor immunity against colorectal cancer

文献类型：期刊论文

作者Yan, Wenlu3,4,6,7; Li, Yu5,6,7; Zou, Yiting5; Zhu, Runqi3,6,7; Wu, Ting1,6,7; Yuan, Wenhui3,6,7; Lang, Tianqun6,7; Li, Yaping2,3,4,5,6,7; Yin, Qi3,4,6,7
刊名INTERNATIONAL JOURNAL OF PHARMACEUTICS
出版日期2023-12-15
卷号648页码:14
关键词Colorectal cancer Irinotecan Imiquimod Micelle Immune response
ISSN号0378-5173
DOI10.1016/j.ijpharm.2023.123583
通讯作者Lang, Tianqun(langtq@lglab.ac.cn) ; Li, Yaping(ypli@simm.ac.cn) ; Yin, Qi(qyin@simm.ac.cn)
英文摘要Irinotecan (IRT), a classic clinical chemotherapeutic agent for treating colorectal cancer, has been found to induce immunogenic cell death (ICD) while exerting cytotoxicity in tumor cells. This effect is likely to be amplified in combination with immune modulators. Unfortunately, free drugs without targeting capacity would receive poor outcomes and strong side effects. To address these issues, in this work, an acid-sensitive micelle based on an amphiphilic poly(beta-amino ester) derivative was constructed to co-deliver IRT and the immune adjuvant imiquimod (IMQ), termed PII. PII kept stable under normal physiological conditions. After internalization by tumor cells, PII dissociated in acidic lysosomes and released IRT and IMQ rapidly. In the CT26 tumor mouse model, PII increased the intra-tumoral SN38 (the active metabolite of IRT) and IMQ concentrations by up to 9.39 and 3.44 times compared with the free drug solution. The tumor inhibition rate of PII achieved 87.29%. This might profit from that IRT induced ICD, which promoted dendritic cells (DCs) maturation and intra-tumoral infiltration of CD8+ T cells. In addition, IMQ enhanced the antigen presenting ability of DCs and stimulated tumor associated macrophages to secrete tumor-killing cytokines. PII provided an effective strategy to combat colorectal cancer by synergy of chemotherapy and immunoregulation.
WOS关键词GENE DELIVERY ; NANOPARTICLES ; DOXORUBICIN ; CELLS
资助项目National Key R & D Program of China[2022YFC3401404] ; National Natural Science Foundation of China[32171315] ; National Natural Science Foundation of China[31930066] ; National Natural Science Foundation of China[32130058] ; Natural Science Foundation of Shandong[ZR2019ZD25] ; Science and Technology Innovation Action Plan Sailing Plan of Shanghai[22YF1460500]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001113218600001
出版者ELSEVIER
源URL[http://119.78.100.183/handle/2S10ELR8/308152]  
专题新药研究国家重点实验室
通讯作者Lang, Tianqun; Li, Yaping; Yin, Qi
作者单位1.Nanjing Med Univ, Sch Pharm, Dept Pharmaceut, Nanjing 211116, Peoples R China
2.Bohai Rim Adv Res Inst Drug Discovery, Yantai 264000, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
4.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Peoples R China
5.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, 501 Haike Rd, Shanghai 201203, Peoples R China
7.Chinese Acad Sci, State Key Lab Drug Res, 501 Haike Rd, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Yan, Wenlu,Li, Yu,Zou, Yiting,et al. Co-delivering irinotecan and imiquimod by pH-responsive micelle amplifies anti-tumor immunity against colorectal cancer[J]. INTERNATIONAL JOURNAL OF PHARMACEUTICS,2023,648:14.
APA Yan, Wenlu.,Li, Yu.,Zou, Yiting.,Zhu, Runqi.,Wu, Ting.,...&Yin, Qi.(2023).Co-delivering irinotecan and imiquimod by pH-responsive micelle amplifies anti-tumor immunity against colorectal cancer.INTERNATIONAL JOURNAL OF PHARMACEUTICS,648,14.
MLA Yan, Wenlu,et al."Co-delivering irinotecan and imiquimod by pH-responsive micelle amplifies anti-tumor immunity against colorectal cancer".INTERNATIONAL JOURNAL OF PHARMACEUTICS 648(2023):14.

入库方式： OAI收割

来源：上海药物研究所

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