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Mitigation of Anti-Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co-Injection of Nano-Rapamycin

文献类型：期刊论文

作者Chang, Ya6,7; Xiong, Wei4,5,6; Zou, Chenming7; Zeng, Ping7; Hou, Jiazhen3,6; Muhitdinov, Bahtiyor2,6; Shen, Yuanyuan7; Huang, Yongzhuo1,4,6; Guo, Shengrong7
刊名SMALL
出版日期2023-09-13
页码12
ISSN号1613-6810
关键词anti-drug antibody co-injection immunological tolerance rapamycin nanoparticles trichosanthin
DOI10.1002/smll.202303916
通讯作者Huang, Yongzhuo(yzhuang@simm.ac.cn) ; Guo, Shengrong(srguo@sjtu.edu.cn)
英文摘要The induction of anti-drug antibody (ADA) is a formidable challenge for protein-based therapy. Trichosanthin (TCS) as a class of ribosome-inactivating proteins is widely studied in tumor treatment. However, the immunogenicity can induce the formation of ADA, which can cause hypersensitivity reactions and neutralize the efficacy of TCS, thus limiting its clinical application in cancer therapy. Here, a promising solution to this issue is presented by co-administration of the rapamycin nanoparticles and TCS. PEGylated rapamycin amphiphilic molecule is designed and synthesized as a prodrug and a delivery carrier, which can self-assemble into a nanoparticle system with encapsulation of free rapamycin, a hydrophobic drug. It is found that co-injection of the PEGylated rapamycin nanoparticles and TCS could mitigate the formation of anti-TCS antibody via inducing durable immunological tolerance. Importantly, the combination of TCS and the rapamycin nanoparticles has an enhanced effect on inhibit the growth of breast cancer. This work provides a promising approach for protein toxin-based anticancer therapy and for promoting the clinical translation. Co-injection of the PEGylated rapamycin nanoparticles and a protein toxin (trichosanthin) can mitigate the formation of anti-drug antibody via inducing durable antigen-specific tolerance. The combination of trichosanthin and the rapamycin nanoparticles yields an enhanced effect to inhibit the growth of breast tumor.image
WOS关键词DENDRITIC CELLS ; T-CELLS ; NANOPARTICLES ; SIROLIMUS ; DELIVERY ; SAFETY ; SITE
资助项目National Key Research and Development Program of China (China)[2021YFE0103100] ; National Key Research and Development Program of China (China)[2021YFC2400600] ; NFSC (China)[81925035] ; NFSC (China)[82073776] ; NFSC (China)[82050410361] ; Department of Science and Technology of Guangdong Province (Highlevel new RD institute)[2019B090904008] ; Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute)[2021B0909050003] ; Zhongshan Municipal Bureau of Science and Technology[LJ2021001] ; Zhongshan Municipal Bureau of Science and Technology[CXTD2022011] ; Chinese Pharmaceutical Association-Yiling Pharm Joint Grants (China)[CPAYLJ201901]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
出版者WILEY-V C H VERLAG GMBH
WOS记录号WOS:001064846100001
源URL[http://119.78.100.183/handle/2S10ELR8/307152]  
专题新药研究国家重点实验室
通讯作者Huang, Yongzhuo; Guo, Shengrong
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Uzbek Acad Sci, Inst Bioorgan Chem, Tashkent 100125, Uzbekistan
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, 138 Xianlin Ave, Nanjing 210023, Peoples R China
4.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China
5.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
7.Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200240, Peoples R China
推荐引用方式
GB/T 7714		 Chang, Ya,Xiong, Wei,Zou, Chenming,et al. Mitigation of Anti-Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co-Injection of Nano-Rapamycin[J]. SMALL,2023:12.
APA Chang, Ya.,Xiong, Wei.,Zou, Chenming.,Zeng, Ping.,Hou, Jiazhen.,...&Guo, Shengrong.(2023).Mitigation of Anti-Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co-Injection of Nano-Rapamycin.SMALL,12.
MLA Chang, Ya,et al."Mitigation of Anti-Drug Antibody Production for Augmenting Anticancer Efficacy of Therapeutic Protein via Co-Injection of Nano-Rapamycin".SMALL (2023):12.

入库方式： OAI收割

来源：上海药物研究所

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