M. Lin, B. Zhao, S. Jia, L. Yan, W. Zhang, Y. Liu
Wenzhou Medical University,
Keywords: polyethylene glycol, graphene, drug delivery, OCM-1 cells, drug delivery
Summary:Choroidal melanoma (CM) is one of the most deadly adult intraocular malignant tumors. Generally CM was dealt by clinical surgery. Secondary damage and even irreversible damage (e.g. loss of the eyeball) to the patients were inevitable. Chemotherapy has been considered as a more suitable alternative for therapy of CM. The traditional chemotherapy drugs, however, are suffered to pass through the so-called Corneal Barrier (CB) and targeted delivery ability to the tumor cells. In our study, we present our recent efforts on nanocarriers from polyethylene glycol modified hydroxylated graphene (PEG-GOH) which show superb performance on passing through the CB and targeted delivery towards OCM-1 cells (a typical cell line of CM). GOH with unique size and huge surface area was synthesized by our recently discovered edge-functionalized ball milling techniques. The as-synthesized GOH exhibited good ability to pass though cell membranes without any damage on cells. Particularly interesting, GOH tended to accumulate around tumor cells due to its slight alkalinity associated with-OH functional groups which were more attractive for the relatively acidic tumor cells than the normal cells. Furthermore, PEG was incorporated to further improve biocompatibility of the drug carriers and targeted ability towards tumor environment. Typical antitumor drug doxorubicin (DOX) was loaded onto the resulting PEG-GOH. For the purpose of comparison, normal ocular cells (ARPE-19) and tumor cells (OCM-1) were co-cultured in a Transwell assay with the addition of the as-prepared PEG-GOH/DOX. A 10% OCM-1 cell viability was obtained after 48 h while more than 50% ARPE-50 cells survived, suggesting excellent targeted suppressing ability of the resulting PEG-GOH/DOX towards tumor cells. This result was further confirmed by using an in vitro 3D tumor model which decreased two times more with PEG-GOH/DOX than that cultured with the pristine DOX.