共载多西他赛和IR820的化疗/光热/光动纳米粒的抗肿瘤增殖及转移作用考察

本课题采用改进的乳化溶剂蒸发法制备聚乳酸-羟基乙酸共聚物(PLGA)-聚乙烯亚胺(PEI)纳米粒,并通过亲疏水作用力和电性吸附原理分别将多西他赛(1)和光敏剂IR820共同装载于PLGA内核和PEI阳离子亲水外壳中。为使纳米粒具有长循环功能,选用负电性肝素(heparin,H)修饰在纳米粒表面使电荷翻转,得到共载药纳米粒(1@IR820/H NPs),从而实现将化疗/光热/光动3种肿瘤治疗相结合,达到理想的抗乳腺癌细胞增殖和转移的治疗效果。制备并表征了所得纳米粒的物理化学性质,并考察了其在体外经近红外光(808 nm)照射处理后对乳腺癌细胞4T1增殖和转移的影响。结果显示,所得的1@IR820/H NPs的粒径为(192.7±4.1)nm,ζ电位为(-22.6±1.9)mV。细胞摄取试验表明,与1@IR820/HNPs共孵育的4T1细胞经近红外光照射处理后,明显增强了摄取能力。体外活性氧试验表明,细胞摄取的增强可提高光动治疗效果。另外,共载药纳米粒的细胞毒性明显高于游离药物。抗肿瘤转移试验表明IR820及共载药纳米粒可抑制肿瘤细胞转移,并且Western Blot技术表征显示抗转移作用...

Combination of Chemo/photothermal/photodynamic Therapy Inhibits Tumor Proliferation and Metastasis by Dual Docetaxel/IR820-loaded Nanoparticles

In this study,docetaxel(1)and photosensitizer IR820 were successfully co-loaded in poly(lacticco-glycolic acid)(PLGA)-cationic polyethyleneimine(PEI)nanoparticles(NPs)using ameliorated emulsion solvent evaporation method,in order to produce a chemo/photodynamic/photothermal therapy.IR820 was jointed with PEI via electrostatic force while 1 was enwrapped by PLGA via hydrophobic interaction.Heparin(H),a common anticoagulant,was employed to modify the nanoparticle at the surface in order to prolong the blood circulation time by charge flipping.The physicochemical properties of the co-loaded NPs(1@IR820/H NPs)were characterized,and the proliferation and metastasis of 4T1 breast cancer cells after incubation with the co-loaded NPs and irradiation with near-infrared(NIR)laser light(808 nm)were investigated.The self-assembled 1@IR820/H NPs presented a particle size of(192.7±4.1)nm andζpotential of(-22.6±1.9)mV.Evaluations of photodynamic performance showed that enhanced cellular uptake by cationic NPs led to better photodynamic effects.The 1@IR820/H NPs showed strong inhibition on tumor cells growth in MTT assay.Furthermore,anti-metastasis effects of IR820 and the nanoparticles at cellular level were verified for the first time by our study.Downregulating matrix metalloproteinase-9(MPP-9)expression was found to be one of the pathways to inhibit the tumor metastasis via Western Blot assay.