The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Caner Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China; College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
College of Pharmaceutical Science, Soochow University, Suzhou 215123, China.
Biomater Adv. 2022 Aug;139:213039. doi: 10.1016/j.bioadv.2022.213039. Epub 2022 Jul 21.
One can enhance the therapeutic index of anti-cancer drugs using albumin as a tumor homing agent for targeted cancer therapy. Herein, we sought to load lapatinib (LAPA) into small albumin-coated biopolymeric (poly-lactic co-glycolic acid (PLGA)) nanoparticles (APL NPs) by an emulsification method to improve the anti-tumor efficacy of lapatinib. The prepared APL NPs exhibited a small spherical core with an average diameter of 120.5 ± 10.2 nm with a narrow particle size distribution, high drug loading capacity (LC of 9.65 ± 1.53 %), good entrapment efficiency (EE of 75.55 ± 3.25 %), enhanced colloidal stability and a pH-responsive controlled drug release profile. Their cell-uptake and cancer cell growth inhibition were significantly higher compared to free LAPA and uncoated PLGA-LAPA (UPL) NPs, most likely because aggressive breast tumor cells over-express albumin receptors and utilize albumin as nutrient source for their growth. In addition, APL NPs possessed enhanced tumor accumulation and prolonged blood residence time compared to free LAPA and UPL NPs, allowing for potent tumor growth inhibition while exhibiting excellent biosafety. In short, the current study exploited a new and simple strategy to concurrently improve the safety and efficacy of LAPA for breast cancer treatment.
可以将白蛋白作为肿瘤归巢剂用于靶向癌症治疗，从而提高抗癌药物的治疗指数。在此，我们试图通过乳化法将拉帕替尼（LAPA）载入小的白蛋白包裹的生物聚合物（聚乳酸-共-羟基乙酸（PLGA））纳米颗粒（APL NPs）中，以提高拉帕替尼的抗肿瘤功效。所制备的 APL NPs 表现出具有小的球形核，平均直径为 120.5 ± 10.2nm，具有较窄的粒径分布、高载药量（LC 为 9.65 ± 1.53%）、良好的包封效率（EE 为 75.55 ± 3.25%）、增强的胶体稳定性和 pH 响应性控制药物释放特性。与游离 LAPA 和未涂层的 PLGA-LAPA（UPL）纳米颗粒相比，它们的细胞摄取和癌细胞生长抑制作用明显更高，这很可能是因为侵袭性乳腺癌细胞过度表达白蛋白受体，并将白蛋白用作其生长的营养源。此外，与游离 LAPA 和 UPL 纳米颗粒相比，APL NPs 具有增强的肿瘤积累和延长的血液滞留时间，从而能够有效抑制肿瘤生长，同时表现出优异的生物安全性。总之，本研究利用一种新的简单策略，同时提高了 LAPA 治疗乳腺癌的安全性和疗效。
