Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Center, Cochin-682041, India.
Nanomedicine (Lond). 2012 Apr;7(4):507-19. doi: 10.2217/nnm.11.139.
Targeted cancer therapy has been extensively developed to improve the quality of treatment by reducing the systemic exposure of cytotoxic drug. Polymeric nanoparticles with conjugated targeting agents are widely investigated because they offer tunability in particle size, drug release profile and biocompatibility.
MATERIALS & METHODS: Here, we have prepared targeted multifunctional nanoparticles composed of a poly(lactic-co-glycolic acid) matrix, ZnS:Mn(2+) quantum dots and camptothecin, and targeted them to EGF receptor overexpressing cells with a cetuximab antibody.
Physicochemical characterization of multifunctional nanoparticles showed stable particles with sizes of <200 nm. In vitro drug release and blood contact studies showed a sustained release profile, with limited hemolysis. In vitro cytotoxicity and cell uptake studies were carried out in A549, KB and MFC-7 cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, FACS, fluorescent microscopic images and spectroflourimetry.
Our studies revealed higher camptothecin activity and uptake in cell lines that overexpress the EGF receptor. All these results suggest that anti-EGF receptor cetuximab-conjugated poly(lactic-co-glycolic acid) multifunctional nanoparticles can be used as a potential nanomedicine against cancer.
靶向癌症疗法已被广泛开发，以通过减少细胞毒性药物的全身暴露来提高治疗质量。与缀合靶向剂的聚合物纳米颗粒已被广泛研究，因为它们可在粒径、药物释放曲线和生物相容性方面进行调整。
在这里，我们制备了由聚（乳酸-共-乙醇酸）基质、ZnS:Mn(2+)量子点和喜树碱组成的靶向多功能纳米颗粒，并将其与曲妥珠单抗抗体靶向到表皮生长因子受体过表达的细胞。
多功能纳米颗粒的理化特性研究表明，其粒径小于 200nm 的颗粒稳定。体外药物释放和血液接触研究表明，具有有限溶血作用的持续释放曲线。在 A549、KB 和 MFC-7 细胞系中，通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐测定法、流式细胞术、荧光显微镜图像和荧光光谱法进行了体外细胞毒性和细胞摄取研究。
我们的研究表明，在过表达表皮生长因子受体的细胞系中，喜树碱的活性和摄取更高。所有这些结果表明，抗表皮生长因子受体曲妥珠单抗缀合的聚（乳酸-共-乙醇酸）多功能纳米颗粒可用作抗癌的潜在纳米药物。
