Layer-by-Layer Assembled Polypeptide Capsules for Platinum-Based Pro-Drug Delivery

Platinum(IV), a pro-drug of platinum(II), was conjugated to poly(L-lysine) (PLL), and then assembled with poly(glutamic acid) (PGA) through a layer-by-layer (LbL) approach on colloidal silica templates. After removal of the templates, biodegradable PGA/PLL-Pt(IV) multilayer capsules (diameter = 0.5 mu m) with 10 mu g of platinum incorporated into each bilayer were obtained. Under acidic and/or reductive conditions, the amount and rate of platinum released from the capsules were increased, which are desirable traits for platinum-based anticancer drug delivery systems. Furthermore, in vitro evaluation showed that the PGA/PLL-Pt(IV) multilayer microcapsule's displayed higher cytotoxicity (IC50Pt = 3.5 mu g/mL) against colon cancer cells CT-26 than that of free cisplatin (IC50Pt = 8.6 mu g/mL). This enhanced cytotoxicity was attributed to the effective internalization of the capsules by the cancer cells, which was observed by confocal laser scanning microscopy (CLSM) imaging.