Improved Protein Toxin Delivery Based on ATTEMPTS Systems

doi:10.2174/1389450118666170302094758

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物制剂研究中心

	Improved Protein Toxin Delivery Based on ATTEMPTS Systems
	Chen, Yingzhi 5; Zhang, Meng 5; Min, Kyoung Ah 1,6; Wang, Huiyuan5 ; Shin, Meong Cheol 2,3,7; Li, Feng 4; Yang, Victor C.3; Huang, Yongzhuo5
刊名	CURRENT DRUG TARGETS
	2018
卷号	19 期号:4 页码:380-392
关键词	Protein toxin ribosome-inactivating protein immunotoxin cell-penetrating peptide (CPP) gelonin tumor-targeting delivery
ISSN号	1389-4501
DOI	10.2174/1389450118666170302094758
文献子类	Review
英文摘要	Background: Ribosome-inactivating proteins (RIPs) are wildly found in multiple species of plants, bacteria and fungi. As a special family of protein toxins, RIPs can inhibit protein synthesis and induce cell death via inactivating ribosome in eukaryotic cells. Thus, RIPs have been applied for anti-tumor therapy in the past two decades. However, because of poor cell permeability, nonselective mode of action for tumor cells, poor pharmacokinetic profiles and immunogenicity, their clinical application has been severely constrained. As an effort to overcome these obstacles, tumor-specific monoclonal antibodies (mAb) have been conjugated to RIPs (forming so called "immunotoxins") specifically to increase their cytotoxicity and provide tumor targeting. Nevertheless, immunotoxins yet have not fully resolved all the issues and critical challenges still remain, such as immunogenicity and inability to penetrate into the deep site of tumor. Objective: To overcome the constrain of immunotoxins, the novel cell-penetrating peptide (CPP)modified ATTEMPTS systems based on combination of CPP-mediated penetration and antibody-mediated tumor targeting, with triggerable drug release function, were developed to achieve effective and safe delivery of protein toxin. Results: The CPP-modified ATTEMPTS systems showed effective protamine-triggered CPP-toxin release and thus enhanced CPP-mediated cellular uptake and cytotoxicity. It also showed antibody-mediated in vivo tumor targeting and significantly increased in vivo tumor growth suppression with limited systematic toxicity. Conclusion: The CPP-modified ATTEMPTS systems were developed and demonstrated as a proof-of-concept for CPP-based protein toxin delivery with triggerable antibody targeting to improve the druggability of protein toxin drugs. The systems showed the potential application of protein toxin clinical translation in anticancer treatment.
资助项目	973 Program, China[2014CB931900] ; 973 Program, China[2013CB932503] ; NFSC[81172996] ; NFSC[81373357] ; NFSC[81361140344] ; NFSC[81422048] ; NFSC[81673382] ; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology[NRF-2015R1A6A3A 01020598] ; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology[NRF-2015R1C1A1A02036781]
WOS关键词	RIBOSOME-INACTIVATING PROTEINS ; CELL-PENETRATING PEPTIDES ; PROOF-OF-CONCEPT ; CANCER-THERAPY ; DRUG-DELIVERY ; FUSION TOXIN ; IN-VITRO ; PHASE-I ; RECOMBINANT IMMUNOTOXIN ; LYMPHOBLASTIC-LEUKEMIA
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000426208400007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272330]
专题	药物制剂研究中心
通讯作者	Shin, Meong Cheol; Huang, Yongzhuo
作者单位	1.Inje Inst Pharmaceut Sci & Res, Gimhae, Gyeongnam, South Korea; 2.Res Inst Pharmaceut Sci, Jinju, Gyeongnam, South Korea; 3.Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA; 4.Hampton Univ, Sch Pharm, Hampton, VA 23668 USA 5.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China; 6.Inje Univ, Coll Pharm, Gimhae, Gyeongnam, South Korea; 7.Gyeongsang Natl Univ, Coll Pharm, Jinju, Gyeongnam, South Korea;
推荐引用方式 GB/T 7714	Chen, Yingzhi,Zhang, Meng,Min, Kyoung Ah,et al. Improved Protein Toxin Delivery Based on ATTEMPTS Systems[J]. CURRENT DRUG TARGETS,2018,19(4):380-392.
APA	Chen, Yingzhi.,Zhang, Meng.,Min, Kyoung Ah.,Wang, Huiyuan.,Shin, Meong Cheol.,...&Huang, Yongzhuo.(2018).Improved Protein Toxin Delivery Based on ATTEMPTS Systems.CURRENT DRUG TARGETS,19(4),380-392.
MLA	Chen, Yingzhi,et al."Improved Protein Toxin Delivery Based on ATTEMPTS Systems".CURRENT DRUG TARGETS 19.4(2018):380-392.