Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy

doi:10.1002/smll.201700666

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

	Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy
	Xu, Jiaojiao 1,2; Xu, Beihua 2; Tao, Jin 2; Yang, Yunxu 2; Hu, Ying 1,2; Huang, Yongzhuo3
刊名	SMALL
	2017-07-26
卷号	13 期号:28
ISSN号	1613-6810
DOI	10.1002/smll.201700666
文献子类	Article
英文摘要	This work aims at developing an immunotherapeutic strategy to deliver a cancer DNA vaccine targeting dendritic cells (DCs), to trigger their maturation and antitumor function, and reduce immune escape using a polymeric nanocomplex of paclitaxel (PTX)-encapsulated sulfobutylether-beta-cyclodextrin (SBE)/mannosylated N,N,N-trimethylchitosan (mTMC)/DNA. To enhance DC-targeting and revoke immunosuppression is the major challenge for eliciting effective antitumor immunity. This codelivery system is characterized by using low-dose PTX as an adjuvant that is included inside SBE, and the PTX/SBE further serves as an anionic crosslinker to self-assemble with the cationic mTMC/DNA polyplexes. This system is used in combination with a microneedle for transcutaneous vaccination. Once penetrating into the epidermis, the mannosylated nanocomplexes would preferentially deliver the pTRP-2 DNA vaccine inside the DCs. Phenotypic maturation is demonstrated by the increased expression of costimulatory molecules of CD80 and CD86, and the elevated secretion of IL-12p70. The mixed leucocyte reactions reveal that the PTX/SBE-mTMC/DNA nanocomplexes enhance the proliferation of CD4+ and CD8+ T cells, and inhibit the generation of immune-suppressive FoxP3+ T cells. The system shows high antitumor efficacy in vivo. The PTX/SBE-mTMC/DNA nanocomplexes for DC-targeted codelivery of DNA vaccine and adjuvant PTX yield synergistic effects on the DC maturation and its presenting functions, thus increasing immune stimulation and reducing immune escape.
资助项目	973 Program, China[2014CB931900] ; 973 Program, China[2013CB932503] ; NSFC[81373357] ; NSFC[81422048] ; NSFC[81673382] ; NSFC[81521005] ; Science and Technology Innovation Team Project of Ningbo Science and Technology Bureau, China[2015C110027] ; Key Laboratory of Ningbo, China[2016A22002]
WOS关键词	REGULATORY T-CELLS ; DENDRITIC CELLS ; IMMUNE TOLERANCE ; GENE DELIVERY ; DNA VACCINE ; IN-VIVO ; CANCER ; ANTIGEN ; IMMUNIZATION ; NANOPARTICLES
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:000405913400006
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272559]
专题	药物制剂研究中心
通讯作者	Hu, Ying; Huang, Yongzhuo
作者单位	1.Wenzhou Med Univ, Dept Med Wenzhou, Wenzhou 325035, Zhejiang, Peoples R China; 2.Zhejiang Pharmaceut Coll, Ningbo 315100, Zhejiang, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Xu, Jiaojiao,Xu, Beihua,Tao, Jin,et al. Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy[J]. SMALL,2017,13(28).
APA	Xu, Jiaojiao,Xu, Beihua,Tao, Jin,Yang, Yunxu,Hu, Ying,&Huang, Yongzhuo.(2017).Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy.SMALL,13(28).
MLA	Xu, Jiaojiao,et al."Microneedle-Assisted, DC-Targeted Codelivery of pTRP-2 and Adjuvant of Paclitaxel for Transcutaneous Immunotherapy".SMALL 13.28(2017).