负载姜黄素的工程化细胞膜纳米颗粒的制备及其用于小鼠乳腺癌治疗的研究OA北大核心CSTPCD

AIM:To investigate the therapeutic efficacy of curcumin(Cur)-loaded engineered cell membrane mimetic nanoparticles(PD1-Cur@PLGA NPs)in treating breast cancer in mice,and to explore their tumor immunomodu-latory effects.METHODS:Engineered mouse breast cancer 4T1-PD1 cell line expressing programmed death 1(PD1)was established,and PD1 expression level was analyzed by flow cytometry.The 4T1-PD1 cell membranes were extracted and coated on the surface of Cur-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(Cur@PLGA NPs)using ice bath sonication to obtain PD1-Cur@PLGA NPs.The Cur loaded in various NPs was detected using UV-visible spectropho-tometry.Particle size and morphology were analyzed by using dynamic light scattering and transmission electron microsco-py.The 4T1 cells were divided into negative control(PLGA NPs and PD1-NVs),experimental(PD1-Cur@PLGA NPs),parallel control(Cur@PLGA NPs),and positive control(Cur)groups.In each group,cell viability was assessed by CCK-8 assay,and cell apoptosis was determined through flow cytometry.To perform treatment experiments in vivo,4T1 cell-bearing tumor mice were randomly divided into PBS,PD1-NVs,and PD1-Cur@PLGA NPs groups.At the end of treat-ments,tissues of major organs were stained to detect pathological changes,as well as indicators of tumor proliferation(Ki67),apoptosis(TUNEL),and infiltration and activity of T cells(CD4+and CD8+)in tumor tissues.RESULTS:The PD1 expression in 4T1-PD1 cell lines reached 78%.PD1-Cur@PLGA NPs exhibited a core-shell structure with particle sizes ranging from 100 to 200 nm.PD1-Cur@PLGA NPs enhanced the biocompatibility compared to free Cur and exhibited a strong apoptosis-inducing effect on 4T1 cells.Compared with control group,PD1-Cur@PLGA NPs significantly inhibited 4T1 breast tumor growth in vivo(P<0.01),without apparent toxic side effects.Treatment with PD1-Cur@PLGA NPs re-duced Ki67 expression,increased cell apoptosis,and enhanced infiltration and activity of CD4+and CD8+T cells in tumor tissues.CONCLUSION:PD1-Cur@PLGA NPs enhanced Cur biocompatibility and exhibited cytotoxicity against mouse breast cancer cells.This nanoformulation demonstrated promising therapeutic efficacy and safety in vivo,exerting poten-tial antitumor immune regulatory effects.