[Experimental research on the treatment of mouse endometriosis model with nanoparticles loaded with CCR5-antibody]

Objective: To investigate whether poly (lactic-co-glycolic acid) (PLGA) as protein delivery vehicles that encapsulate CC chemokine receptor 5 antibody (anti-CCR5) has more suppressive function on macrophages than single anti-CCR5 in mouse endometriosis model. Methods: The PLGA/anti-CCR5 nanoparticles were synthesized. The cumulative release of anti-CCR5 from PLGA/anti-CCR5 nanoparticles was evaluated. The mouse endometriosis model was established and divided into control group, anti-CCR5 group and PLGA/anti-CCR5 group. Meanwhile, ectopic endometrial cells (EEC) and macrophages isolated from peritoneal fluid were cultured in vitro. Flow cytometry was used to detect the proportion of macrophages in the peritoneal fluid of each group. The secretion of interleukin 10 (IL-10) and transforming growth factor β (TGF-β) in each group were determined by ELISA. The proliferation and infiltration of EEC were detected by 5-bromodeoxyuridine proliferation kit and matrigel invasion kit. Results: The PLGA/anti-CCR5 nanoparticles were successfully synthesized. The mouse endometriosis model was established and the EEC and macrophages were cultured. Compared with the anti-CCR5 without nanoparticles, the bioconjugate PLGA/anti-CCR5 nanoparticles could control the release of anti-CCR5 from day 3 to day 24. The proportion of macrophages in PLGA/anti-CCR5 group were gradually reduced compared with those in anti-CCR5 group (P<0.01), the ratios of day 7 [(4.5±1.5)%] and day 3 [(6.3±0.6)%], day 14 [(2.6±0.7)%] and day 7 were significantly different (P<0.01 and P<0.05). PLGA/anti-CCR5 reduced IL-10 and TGF-β levels relative to anti-CCR5 (P<0.01),and decreased gradually on day 3, day 7, and day 14 (P<0.01). Anti-IL-10+anti-TGF-β could reduce the proliferation [(70.8±7.6)%] and invasion ability [(50.2±9.1)%] of EEC (P<0.05). Conclusions: In mouse endometriosis model, PLGA/anti-CCR5 may inhibit the proliferation and invasion of EEC by inhibiting the secretion of IL-10 and TGF-β by macrophages, suggesting that it provide a new idea for the treatment of clinical endometriosis.