叶酸功能化纳米平台共递送PTX/DOX用于体外抗三阴性乳腺癌研究OA

Objective To develop a folic acid(FA)-modified pullulan(PUL)-based nano co-delivery platform(P/D NP)with active targeting and pH-sensitive sustained-release properties,aiming to overcome poor tumor targeting and low co-delivery efficiency associated with paclitaxel(PTX)and doxorubicin(DOX)combination chemotherapy,and to provide a new strategy for precision treatment of triple-negative breast cancer(TNBC).Methods An amphiphilic prodrug conjugate(FA-PUL-PTX)was synthesized through sequential esterification and amidation reactions,followed by self-assembly with DOX to form the co-delivery nanoparticles(P/D NPs).The chemical structure was confirmed by Fourier transform infrared spectroscopy.Particle size,zeta potential,and morphology were characterized using dynamic light scattering and transmis-sion electron microscopy.Drug loading contents and encapsulation efficiencies were calculated.In vitro release profiles were evaluated by dialysis at pH 7.4 and pH 5.5.Cellular uptake of FA-modified versus unmodified nanoparticles was ob-served under an inverted fluorescence microscope.Cytotoxicity,cell migration,and apoptosis were assessed by MTT assay,scratch wound healing assay,and acridine orange/ethidium bromide(AO/EB)staining,respectively.Results The optimal mass ratio of FA-PUL-PTX to DOX was determined to be 1:1.0.The obtained P/D NPs exhibited a uniform size of(220.12±21.28)nm,a polydispersity index of(0.192±0.014),a zeta potential of(-29.18±3.14)mV,and a regular spherical morphology.The drug loading amounts for PTX and DOX were(7.88±1.03)％and(1.27±0.73)％,and the encapsulation effi-ciencies were(80.01±4.59)％and(7.37±0.98)％,respectively.The P/D NPs showed pronounced sustained release behavior,with higher cumulative release at pH 5.5 than at pH 7.4 over 48 h.FA modification significantly enhanced the uptake of nanoparticles by MDA-MB-231 cells.Compared with the free drug combination,P/D NPs more effectively inhibited cell proliferation and migration and induced apoptosis(P<0.05).Conclusion The prepared FA-functionalized nano co-delivery platform(P/D NPs)possesses uniform particle size,good dispersibility,and pH-sensitive drug release performance.It was effectively taken up by MDA-MB-231 cells and exhibited stronger antitumor activity than the free drug combination in vi-tro.