A dual stimuli-responsive star-shaped nanocarrier as de novo drug delivery system for chemotherapy of solid tumors

Abstract

A novel pH- and temperature-responsive star-shaped terpolymer, namely star shaped-poly(e-caprolactone)-grafted-[poly(N,N′-dimethylamino)ethyl methacrylate-block-poly(N-isopropylacrylamide)] [s-PCL-g-(PDMAEMA-b-PNIPAAm)], was synthesized by combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP), and its potential as smart drug delivery system (DDS) for chemotherapy of solid tumors (human breast cancer) was investigated preliminary. The structure of the fabricated polymers were characterized using Fourier transform infrared (FTIR) and proton magnetic resonance (1H NMR) spectroscopies. The average molecular weights of the synthesized polymers were calculated using both 1H NMR spectroscopy and gel permeation chromatography (GPC) analysis. The self-assembly behavior of the fabricated s-PCL-g-(PDMAEMA-b-PNIPAAm) terpolymer under pH and thermal stimuli were investigated using dynamic light scattering (DLS) equipment. The methotrexate (MTX) loading capacity of the fabricated DDS was calculated to be 36.9 ± 4.1%. As pH- and thermal-triggered drug release behavior results, at pH 5 and temperature of 41 °C, the developed DDS exhibited higher drug release value, which qualified it for cancer chemotherapy according to abnormal environmental feature of cancerous cells. The MTX-loaded terpolymer exhibited higher anticancer efficiency in comparison with free MTX especially in time period of 48 h, mainly due to its slow drug release behavior as well as long circulation time of the developed DDS.