Kumar Rajiv, Kulkarni Apurva, Nabulsi Jude, Nagesha Dattatri K, Cormack Robert, Makrigiorgos Mike G, Sridhar Srinivas
Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, MA 02115 ; Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Drug Deliv Transl Res. 2013 Aug 1;3(4):299-308. doi: 10.1007/s13346-012-0124-9.
The advent of nanotechnology has bolstered a variety of nanoparticles based platforms for different biomedical applications. A better understanding for engineering novel nanoparticles for applications in cancer staging and therapy requires careful assessment of the nanoparticle's physico-chemical properties. Herein we report a facile synthesis method for PEGylated PLGA nanoparticles encapsulating anti-cancer drug doxorubicin for cancer imaging and therapy. The simple nanoprecipitation method reported here resulted in very robust PEGylated PLGA nanoparticles with close to 95% drug encapsulation efficiency. The nanoparticles showed a size of ~110 nm as characterized by TEM and DLS. The nanoparticles were further characterized by optical UV-Visible and fluorescence spectroscopy. The encapsulated doxorubicin showed a sustained release (>80%) from the nanoparticles matrix over a period of 8 days. The drug delivery efficiency of the nanoparticles was confirmed in vitro confocal imaging with PC3 and HeLa cell lines. In vitro quantitative estimation of drug accumulation in PC3 cell line showed a 22 times higher concentration of drug in case of nanoparticles based formulation in comparison to free drug and this was further reflected in the in vitro cytotoxicity assays. Overall the synthesis method reported here provides a simple and robust PLGA based platform for efficient drug delivery and imaging of cancer cells in vitro and in vivo.
纳米技术的出现推动了各种基于纳米颗粒的平台在不同生物医学应用中的发展。要更好地理解如何设计用于癌症分期和治疗的新型纳米颗粒，需要仔细评估纳米颗粒的物理化学性质。在此，我们报告了一种简便的合成方法，用于制备包裹抗癌药物阿霉素的聚乙二醇化聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒，用于癌症成像和治疗。本文报道的简单纳米沉淀法产生了非常稳定的聚乙二醇化PLGA纳米颗粒，药物包封效率接近95%。通过透射电子显微镜（TEM）和动态光散射（DLS）表征，纳米颗粒的尺寸约为110 nm。纳米颗粒还通过紫外可见光谱和荧光光谱进一步表征。包裹的阿霉素在8天内从纳米颗粒基质中持续释放（>80%）。纳米颗粒的药物递送效率在PC3和HeLa细胞系的体外共聚焦成像中得到证实。在PC3细胞系中对药物积累的体外定量估计显示，与游离药物相比，基于纳米颗粒的制剂中药物浓度高22倍，这在体外细胞毒性试验中也得到了进一步体现。总体而言，本文报道的合成方法提供了一个简单而稳定的基于PLGA的平台，用于体外和体内癌细胞的高效药物递送和成像。
