Evaluation of PLGA containing anti -CTLA4 inhibited endometriosis progression by regulating CD4 + CD25 + Treg cells in peritoneal fluid of mouse endometriosis model

Liu Q, Qi Liu, Pingchuan Ma, Ma P, Liu L, Lanxia Liu, Ma G, Guilei Ma, Ma J, Jingjing Ma, Xiaoxuan Liu, Liu X, Liu Y, Yijin Liu, Lin W, Wanjun Lin, Zhu Y, Yingjun Zhu
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2016 · vol. 96 , pp. 542–550 · doi:10.1016/j.ejps.2016.10.031 · PMID:27989857 · W2540488263
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PLGA containing anti-CTLA4 therapy inhibited endometriosis progression in a mouse model by regulating CD4+CD25+ Treg cells in peritoneal fluid.

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Abstract

Our study investigated poly(lactic-co-glycolic acid) (PLGA) as protein delivery vehicles encapsulate CTLA-4-antibody (anti-CTLA-4) which is essential for CD4+CD25+Treg cells suppressive function exposing superior potential for inhibiting endometriosis progress in mouse model than single anti-CTLA-4. Anti-CTLA-4 loaded PLGA combined to ligands CTLA-4 in surface of CD4+CD25+Treg cells which distributed in peritoneal fluid of mouse endometriosis model. The particle size, zeta potential of the anti-CTLA-4 loaded nanoparticles was detected by dynamic light scattering. Morphology of nanoparticles was evaluated by transmission electron microscopy (TEM). Confocal laser scanning microscopy (CLSM) indicated distribution of anti-CTLA-4 with PLGA or without in peritoneal fluid. Cumulative anti-CTLA-4 release from nanoparticles was evaluated by Micro BCA assay. The percentage of CD4+CD25+Treg cells in peritoneal fluid was demonstrated by flow cytometer. In vitro experiment we co-culture ectopic endometrial cells (EEC) with isolated CD4+CD25+Treg cells in peritoneal fluid (PF), proliferation and invasion of ectopic endometrial cells (EEC) was measured by BrdU ELISA assay and Matrigel invasion assay. In comparison with anti-CTLA-4 without nanoparticles, the bioconjugates PLGA/anti-CTLA-4 were tolerated in peritoneal fluid with a controlled release of anti-CTLA-4 in 3, 7, 14days. Moreover, PLGA/anti-CTLA-4 had superior protective regulation ability to reduce level of CD4+CD25+Treg cells in peritoneal fluid. Most strikingly, in vitro experiment, PLGA/anti-CTLA-4 exhibited better ability in inhibiting proliferation and invasion of ectopic endometrial cells in co-culture system compared with anti-CTLA-4. Progressively, PLGA/anti-CTLA-4 had better suppressive activity to inhibited IL-10 and TGF-beta secreted by CD4+CD25+Treg cells which indicating that PLGA/anti-CTLA-4 suppressed cells proliferation and invasion through reduced IL-10 and TGF-beta production. Thus, PLGA/anti-CTLA-4 may be a potential strategy for endometriosis therapy.

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Condition tags

endometriosis

MeSH descriptors

Antibodies CTLA-4 Antigen Endometriosis Lactic Acid Polyglycolic Acid T-Lymphocytes, Regulatory Animals Antibodies Ascitic Fluid Ascitic Fluid Cell Culture Techniques Cell Proliferation CTLA-4 Antigen Drug Carriers Drug Carriers Endometriosis Endometriosis Female Humans Interleukin-10

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