共载藤黄酸和Cypate纳米粒子用于肿瘤的化疗-光热协同治疗

Co-loaded gambogic acid and Cypate nanoparticles for synergetic chemotherapy and photothermal therapy of cancer

目的制备以乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic),PLGA]为载体共载藤黄酸(gambogic acid,GA)和光热剂Cypate的纳米粒子(GA-Cy-PNs),实现化疗联合光热治疗以提高抗肿瘤治疗效果。方法使用油/水乳化法制备GA-Cy-PNs;利用透射电镜评价纳米粒子的结构;通过马尔文激光粒度仪测定粒径分布和Zeta电位,考察纳米粒子贮存及血浆稳定性;利用紫外分光光度法考察GA和Cypate的包封率和载药量;采用透析法研究GA-Cy-PNs体外释放行为;使用近红外热成像仪评价光热转换能力和光热稳定性;采用激光共聚焦显微镜观察近红外激光照射对4T1细胞和HepG2细胞摄取GA-Cy-PNs能力的影响;采用CCK-8法考察纳米粒子对4T1细胞和HepG2细胞的毒性。结果制备的GA-Cy-PNs呈球形,粒径均一,均匀分散,能被较好的贮存并具有良好的血浆稳定性;GA和Cypate的包封率分别为80.76%和82.73%,载药量分别为3.51%和7.19%,在酸性条件下,GA释放速度加快;光热测试表明GA-Cy-PNs具有良好的光热转换能力和优异的热稳定性;近红外激光照射能促进细胞对纳米粒子的摄取;体外生物安全性评估试验表明,GA-Cy-PNs具有良好的生物安全性和生物相容性;细胞毒性试验证实在近红外光照射下,联合化疗药物的治疗效果明显优于单一治疗。结论GA-Cy-PNs是一种具有化疗与光热联合治疗功能的纳米粒子,展现出明显地抗肿瘤细胞活性,为肿瘤的协同治疗提供新的研究策略。

Objective The poly(lactic-co-glycolic)(PLGA)nanoparticles(GA-Cy-PNs)loaded with gambogic acid(GA)and the photothermal agent Cypate was prepared,to achieve the combination of chemotherapy and photothermal therapy and enhance antitumor effect.Methods GA-Cy-PNs were fabricated through an oil-in-water(O/W)emulsion technique.The morphological features of the nanoparticles were observed through a transmission electron microscopy.The average size,polydispersity index,Zeta potential and the stability of nanoparticles were determined by dynamic light scattering.The drug loading efficiencies and the coating rates of GA and Cypate were quantified by a UV-visible spectrometer.The GA-Cy-PNs releasein vitro was studied by dialysis method.The photothermal effect and photothermal stability of GA-Cy-PNs were recorded using an infrared thermal imaging camera.The cellular uptake behaviors of GA-Cy-PNs in 4T1 and HepG2 cells with or without the NIR laser irradiation were studied using confocal laser scanning microscopy.The cytotoxicity of the nanoparticles on 4T1 and HepG2 cells was investigated by a CCK-8 assay.Results The nanoparticles exhibited a uniform spherical shape with high dispersity and good stability.The encapsulation efficiencies of GA and Cypate were measured to be 80.76%and 82.73%,and the drug loading efficiencies were 3.51%and 7.19%,respectively.Under acidic condition,GA can be rapidly released from the nanoparticle.The photothermal test demonstrated that GA-Cy-PNs had good photothermal conversion properties and excellent photothermal stability.The results of the in vitro biosafety showed that GA-Cy-PNs had the good safety and compatibility.NIR laser irradiation could promote the nanoparticles uptake of 4T1 and HepG2 cells.The cytotoxicity test confirmed that the combination of chemotherapy drugs and photothermal therapy can achieve stronger cytotoxicity than that of photothermal therapy alone or chemotherapy alone.Conclusion GA-Cy-PNs can achieve chemo-photothermal combination therapy and possess an obvious antitumor efficacy,providing a new research idea for the synergistic treatment of cancer.