Construction of pH-Responsive Paclitaxel-exosome Composite Nanocarriers and Their Inhibitory Effect on the Proliferation of Endometrial Cells

LIAO Lan-jin; CHEN Hui-ping

Abstract：Objective: To construct a pH-responsive paclitaxel (PTX)-exosome composite nanocarrier and investigate its inhibitory effect on the proliferation of endometrial cancer cells (HEC-1A). Methods: PTX was loaded into exosomes derived from adipose mesenchymal stem cells using the thin-film hydration method, and modified with polyethylene glycol-polylactic-co-glycolic acid (PEG-PLGA) to form nanocarriers (PTX-Exo-NPs). The particle size and morphology were detected by nanoparticle size and Zeta potential analyzer; drug encapsulation efficiency and drug loading capacity were determined by high-performance liquid chromatography; drug release behavior was evaluated in vitro under simulated acidic (pH 5.5) and physiological (pH 7.4) conditions; MTT assay and flow cytometry were used to detect the effects of the carrier on the proliferation, apoptosis, and cell cycle distribution of HEC-1A cells. Results: PTX-Exo-NPs exhibited a uniform spherical shape with a particle size of (128.5±5.2) nm, PTX encapsulation efficiency of 92.3%±2.1%, and drug loading capacity of 15.6%±0.8%. Drug release rate in the acidic environment (85.3%±2.1% within 72 h) was significantly higher than that in the physiological environment (48.0%±1.7%). In vitro experiments demonstrated that the proliferation inhibition rate of PTX-Exo-NPs on HEC-1A cells was higher than that of free PTX, with a lower IC50 (0.64 μM vs 4.70 μM), and could induce cell apoptosis (apoptosis rate: 28.7%±2.1% vs 14.2%±1.5%) and promote cell cycle arrest (G2/M rate: 45.3%±3.2%). Conclusion: PTX-Exo-NPs exhibit pH-responsive characteristics, which can target drug release through the acidic microenvironment, enhance the proliferation inhibition and pro-apoptotic effect on endometrial cancer cells, thus serving as a potential strategy for targeted therapy of endometrial tumors.