Using Poly(N‐isopropylacrylamide) and Poly(ethyleneglycol) Grafted Polycarbodiimides As Unique Nanocarriers for Hydrophobic Form of the Doxorubicin (DOX)

Amphiphilic helical polycarbodiimides bearing side chains with terminal alkyne groups provide a unique platform for construction of polymeric micelles. Incorporation of propargyl pendants into polyguanidine backbone allowed post-polymerization modification with azide terminated, random coil, poly(N-isopropylacrylamide), PNIPAM15K and poly(ethyleneglycol), PEG2K moieties using copper-catalyzed click reaction (CuAAC). Thus, four new amphiphilic brush copolymers with varying grafting density were synthesized and their self-assembly behavior in aqueous medium was studied by combination of TEM, SEM, AFM, and optical microscopy techniques. It was shown the formation of micellar structures at critical micelle concentration (CMC) ranging from 1.58 x 10(-5) to 1.05 x 10(-3)mg mL(-1). A hydrophobic drug doxorubicin (DOX) was then encapsulated successfully into these micellar structures with encapsulation efficiency (EE) falling in the range from 16% to 27%. Further, the cellular uptake studies were carried out by using HeLa cells and the cytotoxic activity of DOX-loaded micelles was determined to be less than 65% of cell viability at a concentration of 0.250 mg mL-1. Fluorescence microscopy imaging revealed importing the micelles into the cells by endocytosis and internalization of the DOX into nucleus of the HeLa cells.