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Evaluation of PLGA containing anti-CTLA4 inhibited endometriosis progression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model.
Liu, Qi; Ma, Pingchuan; Liu, Lanxia; Ma, Guilei; Ma, Jingjing; Liu, Xiaoxuan; Liu, Yijin; Lin, Wanjun; Zhu, Yingjun.
Afiliação
  • Liu Q; Department of Obstetrics & Gynecology, Graduate School of Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China.
  • Ma P; Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, 156 San Ma Road, Nankai District, Tianjin 300100,China.
  • Liu L; Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, China.
  • Ma G; Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, China.
  • Ma J; Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, China.
  • Liu X; Lab of Bioengineering, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, China.
  • Liu Y; Department of Obstetrics & Gynecology, Graduate School of Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China.
  • Lin W; Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, 156 San Ma Road, Nankai District, Tianjin 300100,China.
  • Zhu Y; Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, 156 San Ma Road, Nankai District, Tianjin 300100,China. Electronic address: zhuyj8072@sina.com.
Eur J Pharm Sci ; 96: 542-550, 2017 Jan 01.
Article em En | MEDLINE | ID: mdl-27989857
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Poliglicólico / Linfócitos T Reguladores / Ácido Láctico / Endometriose / Antígeno CTLA-4 / Anticorpos Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Eur J Pharm Sci Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ácido Poliglicólico / Linfócitos T Reguladores / Ácido Láctico / Endometriose / Antígeno CTLA-4 / Anticorpos Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Revista: Eur J Pharm Sci Ano de publicação: 2017 Tipo de documento: Article