Thermo-responsive nanocarrier based on poly(N-isopropylacrylamide) serving as a smart doxorubicin delivery system

Abstract

Smart temperature- and pH-responsive nanocarriers could be considered as potent vehicle in drug delivery systems. By this means, a thermo-responsive polymeric nanocarrier based on a random copolymer of poly(N-isopropylacrylamide-co-acrylamide) was prepared using controlled polymerization technique known as reversible addition fragmentation chain transfer (RAFT) polymerization. The presence of hydrophilic group in the chain, acrylamide, enhanced the lower critical solution temperature (LCST) to 37 °C in agreement with body normal temperature and made the structure suitable for drug delivery purposes. To reach this goal, the as-prepared structure was modified with hydrazine and then the anti-cancer drug, doxorubicin, was conjugated to hydrazine-modified chains through a Schiff-base linkage (acid-cleavable bond) to provide nanodrug carrier capable of responding to heat and pH. The product of each step was characterized with defined techniques. 1HNMR spectroscopy provided data for molecular weight determination. The hydrodynamic size was figured out by dynamic light scattering to be less than 300 nm. A comprehensive study on the topology of nanodrug carrier was performed by scanning electron microscopy, and the structural changes below and above the LCST were followed by transmission electron microscopy and atomic force microscopy which showed coil-like composition to globule assembly at temperature above the LCST. Furthermore, the release pattern of nanodrug carrier was assessed in the simulated medium of healthy organs or cancer tissue with pH 7.4 and 5 (37 and 42 °C). Finally, the cytotoxicity assay was performed on breast cancer/MCF-7 cell line which showed high potential of nanodrug carrier as a highly intelligent anti-cancer agent.