Multifunctional block copolymer nanocarriers for co-delivery of silver nanoparticles and curcumin: Synthesis and enhanced efficacy against tumor cells

Functional multilayer polymeric micelles were obtained by self-assembly of a polyethylene oxide)-b-poly(n-butyl acrylate)-b-poly(acrylic acid) (PEO113-b-PnBA(235)-b-PAA(14)) tri-block terpolymer and exploited as template for the synthesis of silver nanoparticles and loading of anti-cancer agents. The terpolymer was synthesized by atom transfer radical polymerization of n-butyl acrylate and tert-butyl acrylate (tBA), initiated by a PEO-based macroinitiator. Then, PtBA blocks were converted into PAA by selective hydrolysis. PEO113-b-PnBA(235)-b-PAA(14) terpolymer formed nano-sized spherical micelles in the concentration range from 1 to 10 mg mL(-1) as confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The presence of PAA chains in the middle micellar layer allowed loading of silver ions and subsequent UV-induced synthesis of silver nanoparticles within the micelles. After that, the anti-cancer drug curcumin was loaded in the hydrophobic PnBA micellar cores. The effect of combination of two anti-cancer agents, spontaneously released from the micelles, on the vitality of acute myeloid leukemia (HL-60), its multidrug-resistant subline HL-60/DOX and human urinary bladder carcinoma (EJ) cells was assessed. The in vitro experiments revealed enhanced efficacy in regard to the cytotoxic activity of silver nanoparticles and curcumin. (C) 2016 Elsevier Ltd. All rights reserved.