Ou, Wenquan; Thapa, Raj Kumar; Jiang, Liyuan; Soe, Zar Chi; Gautam, Milan; Chang, Jae-Hoon; Jeong, Jee-Heon; Ku, Sae Kwang; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh
Journal of controlled release : official journal of the Controlled Release Society
2018Jul ; 281 ( 7 ) :84-96.
PMID : 29777794
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Ou, Wenquan - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
Thapa, Raj Kumar - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
Jiang, Liyuan - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
Soe, Zar Chi - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
Gautam, Milan - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
Chang, Jae-Hoon - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
Jeong, Jee-Heon - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea.
Ku, Sae Kwang - Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University, Gyeongsan 712-715, South Korea.
Choi, Han-Gon - College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, 55, Hanyangdaehak-ro, Sangnok-gu, Ansan 426-791, South Korea.
Yong, Chul Soon - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea. Electronic address csyong@ynu.ac.kr.
Kim, Jong Oh - College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyeongsan 712-749, South Korea. Electronic address jongohkim@yu.ac.kr.
ABSTRACT
Immunosuppression in tumor microenvironments induced by regulatory T (Treg) cells is regarded a critical mechanism of tumor immune escape and poses a major impediment to cancer immunotherapy. In this study, we developed tLyp1 peptide-conjugated hybrid nanoparticles for targeting Treg cells in the tumor microenvironment. The tLyp1 peptide-modified hybrid nanoparticles presented good stability and effective targeting to Treg cells, and they enhanced the effect of imatinib in downregulating Treg cell suppression through inhibition of STAT3 and STAT5 phosphorylation. In addition, an in vivo study revealed high tumor accumulation of the hybrid nanoparticle. Specifically, prolonged survival rate, enhanced tumor inhibition, reduced intratumoral Treg cells, and elevated intratumoral CD8(+) T cells against tumor were observed when combined with checkpoint-blockade by using anti-cytotoxic T-lymphocyte antigen-4 antibody. This study provided groundwork for a repertoire of nanoparticle-based drugs for targeting and modulating Treg cell function in the tumor microenvironment and for improving antitumor immunotherapy. CI - Copyright ??2018. Published by Elsevier B.V.
keyword
CTLA-4; Cancer immunotherapy; Hybrid nanoparticles; Imatinib; Treg cell; tLyp1 peptide
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