化学-光热联合治疗的靶向铂药纳米微球的构建及体外评价

唐瑾; 王宇; 杨岁; 孙玉

doi:10.11665/j.issn.1000-5048.20210605

化学-光热联合治疗的靶向铂药纳米微球的构建及体外评价

唐瑾¹,
王宇¹,
杨岁¹,
孙玉^1,2

1.
皖南医学院药学院，芜湖 241002
2.
皖南医学院医用材料合成应用研究所，芜湖 241002

基金项目: 安徽省高校科学研究资助项目（No.KJ2020A0613）；皖南医学院第三批学术和技术带头人及后备人选资助项目（No.201908）

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出版历程
- 收稿日期: 2021-06-30
- 修回日期: 2021-11-04
- 刊出日期: 2021-12-24

Construction and in vitro evaluation of targeted cisplatin-loaded nanoparticles for chemo-photothermal cancer therapy

1.
School of Pharmacy, Wannan Medical College, Wuhu 241002
2.
Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu 241002, China

Funds: This study was supported by the Scientific Research Project of Universities in Anhui Province (No. KJ2020A0613); and the Foundation for the Third Batch of Academic and Technical Leaders and Reserve Candidates of Wannan Medical College (No.201908)

摘要

摘要: 为提高顺铂的治疗效果并减少副作用，构建了一种具有化学-光热联合疗效的靶向铂药递送体系。以聚乙二醇-聚乳酸共聚物为载体，采用超声乳化法制备负载顺铂和光敏剂吲哚菁绿的纳米微球，再由西妥昔单抗进行表面修饰，从而制备西妥昔单抗修饰的近红外活化的载药纳米微球（CPINPs）。通过表征平均粒径、Zeta 电位、单抗偶联率、光热效应等考察其理化性质；通过激光共聚焦显微镜测定体外细胞摄取情况；通过CCK8实验评价体外抗肿瘤活性。结果表明，所制备的CPINPs纳米微球平均粒径为（263.9 ± 3.73） nm，多分散指数为0.18 ± 0.03，Zeta电位为-（23.43 ± 0.42） mV，单抗偶联率为（44.0 ± 1.72）%；体外光热实验显示，经近红外光照射后的CPINPs会产生导致肿瘤细胞死亡的光热效应；体外细胞摄取实验结果表明，近红外光对细胞摄取有促进作用，A549细胞会选择性地摄取更多受近红外照射过的CPINPs；体外细胞毒性实验表明，近红外光照射处理的CPINPs具有化学-光热联合治疗效果，其抑制A549细胞增殖的能力高过游离顺铂和无光照处理组，给药24 h的IC₅₀为（8.67 ± 0.04） μmol/L。实验结果表明，本研究构建的多功能给药系统有望成为一种更为高效的肺癌靶向治疗方法。
- 化学-光热治疗 /
- 靶向运输 /
- 西妥昔单抗 /
- 顺铂 /
- 纳米微球
Abstract: To improve the therapeutic effect of cisplatin and reduce its side effects, a multifunctional drug delivery system with targeted and chemo-photothermal effect was constructed.Using polyethylene glycol polylactic acid block copolymer as a carrier, nanoparticles loaded with antitumor drug cisplatin and photosensitizer indocyanine green were prepared by ultrasonic emulsification, and the surface was then modified by cetuximab to prepare cetuximab-decorated and near-infrared (NIR)-activated nanoparticles (CPINPs).The physicochemical properties were characterized by mean particle size, Zeta potential, mAb conjugating rate and photothermal effect; the in vitro cell uptake was measured by laser confocal microscopy; and the in vitro antitumor activity was evaluated by CCK8 assay.The results indicated that CPINPs had mean particle diameter of (263.9 ± 3.73) nm, polydispersity index of 0.18 ± 0.03, Zeta potential of -(23.43 ± 0.42) mV, and cetuximab conjugating rate of (44.0 ± 1.72)%.The in vitro photothermal experiments showed that CPINPs upon NIR irradiation induced a photothermal effect, thus destroying the tumor cells. The in vitro cell uptake experiments demonstrated that NIR irradiation could promote cell uptake, and that more CPINPs were effectively internalized into A549 cells. The in vitro cytotoxicity test indicated that CPINPs treated with NIR irradiation had the effect of combined chemo-photothermal therapy, leading to higher cytotoxicity than that of free cisplatin or treatment without NIR, with IC₅₀ values being (8.67 ± 0.04) μmol/L for 24 h incubation.To sumup the multifunctional drug delivery system constructed in the current work expected to be a more efficient targeted therapy strategy for lung cancer.
- chemo-photothermal therapy /
- targeted delivery /
- cetuximab /
- cisplatin /
- nanoparticles

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