Meng W, Parker T L, Kallinteri P, Walker D A, Higgins S, Hutcheon G A, Garnett M C
School of Pharmacy, University of Nottingham, Nottingham, NG7 2RD, UK.
J Control Release. 2006 Dec 1;116(3):314-21. doi: 10.1016/j.jconrel.2006.09.014. Epub 2006 Oct 3.
A useful route for the development of antitumour therapies is by creating improved methods for delivering therapeutic agents to tumour cells or subcellular compartments and increasing retention of drugs within target cells. In this study, we have characterized nanoparticle (NP) uptake and metabolism by DAOY cells, a human medulloblastoma cell line. NPs were formed from a novel polymer, poly (glycerol-adipate) (PGA), containing Rhodamine B Isothiocyanate (RBITC) as a fluorescent marker. It was observed that the cellular uptake of NPs depends on the incubation time and the concentration of NPs in the culture medium. The studies of retention and metabolism of NPs within cells indicated that 1) faster degradation of NPs within cells compared with that in cell culture medium in vitro; 2) a small fraction of NPs were recycled back to the outside of cell, whereas most NPs entered endosomes and lysosomes; and 3) recycled NPs were re-taken up in the following 2 h incubation time. These studies thus suggested that PGA NPs could be used for localising therapeutic agents into cells, and could provide prolonged drug effects because of their long sustained release in physiological conditions and their rapid release when taken up into cells.
开发抗肿瘤疗法的一条有效途径是创造改进的方法，将治疗剂递送至肿瘤细胞或亚细胞区室，并提高药物在靶细胞内的保留率。在本研究中，我们已对人髓母细胞瘤细胞系DAOY细胞摄取和代谢纳米颗粒（NP）的情况进行了表征。NP由一种新型聚合物聚（甘油己二酸酯）（PGA）形成，其中含有异硫氰酸罗丹明B（RBITC）作为荧光标记物。据观察，NP的细胞摄取取决于孵育时间和培养基中NP的浓度。细胞内NP的保留和代谢研究表明：1）与体外细胞培养基中相比，NP在细胞内降解更快；2）一小部分NP被循环回细胞外，而大多数NP进入内体和溶酶体；3）循环的NP在接下来2小时的孵育时间内被重新摄取。因此，这些研究表明PGA NP可用于将治疗剂定位到细胞中，并且由于其在生理条件下的长期持续释放以及被细胞摄取时的快速释放，可提供延长的药物作用。
