摘要
癌细胞的有效治疗主要是药物进入癌细胞核中有效释放,进而破坏DNA而使得癌细胞死亡~(1,2)。目前,由于载药材料较大的尺寸或药物释放在细胞质中,致使对癌细胞达不到较好的治疗效果。本论文采用水热法,一步原位修饰还原氧化石墨烯得到茶多酚还原修饰的氧化石墨烯(TPG),并采用高速离心(13000rpm)取上清液得到片层较小的材料备用。实验表明,TPG对阿霉素(DOX)的最大吸附容量高达3.430×10~6 mg/g,且显示了p H依赖的释放行为,在pH=5.0(癌细胞内涵体的pH值)释放效果优于7.4(生理学pH)和6.8(癌组织的pH),表明了TPG-DOX在血液循环中具有一定的稳定性,以及进入癌细胞后药物可以有效地释放,从而有利于对癌细胞的有效治疗。细胞实验表明了TPG对正常细胞(L929)友好,载药后可以通过细胞吞噬作用进入癌细胞的细胞核中,释放出DOX,通过细胞凋亡途径来进行癌细胞的治疗。图1概括了文章的整体思路。双功能的药物载体TPG在生物医药和癌细胞治疗领域带来了新的希望。
Considerable efforts have been taken to carry the antitumor drug into cell nucleus, release, and intercalate with DNA in order to kill tumor cells. In this work, the obtained TPG shows an efficient loading capacity of doxorubicin(DOX) as high as 3.430×10~6 mg/g, and exhibits a pH-responsive release behavior. In addition, cellular experiments shows TPG is very friendly to L929 cells, while can promote anticancer drug uptake by cell phagocytosis, mainly locate in cell nucleus and promote tumor cells death. Together, the high drug payload and enhanced antitumor efficacy render our developed system promising for biomedical applications and cancer therapy.
引文
[1]Momparler,R.L.;Karon,M.;Siegel,S.E.;Avila,F.Cancer Res.1976,36:2891.
[2]Fornari,F.A.;Randolph,J.K.;Yalowich,J.C.;Ritke,M.K.;Gewirtz,D.A.Mol.Pharmacol.1994,45:649.