PH-responsive nanosystems based on reduced graphene oxide grafted with polycaprolactone-block-poly(succinyloxyethylmethacrylate) for doxorubicin release

Abstract

pH-responsive nanocarriers were synthesized via polycaprolactone-b-poly(succinyloxyethylmethacrylate) copolymers grafted onto reduced graphene oxide (rGO-g-PCL-b-PSEMA) for anticancer drug delivery applications. For this propose, e-caprolactone monomer was polymerized from –OH groups of rGO with ring-opening polymerization (ROP) to obtain polycaprolactone grafts (rGO-g-PCL). In the next step, 2-hydroxyethylmethacrylate monomer was polymerized from PCL end through atom transfer radical polymerization to afford rGO-g-PCL-b-poly(hydroxyethylmethacrylate) (PHEMA). The pH-responsive rGO-g-PCL-b-PSEMA was obtained by reacting rGO-g-PCL-b-PHEMA with excess succinic anhydride in pyridine under mild conditions. The pH sensitivity of nanosystems was confirmed via dynamic light scattering at pH values of 4 and 7.4. Doxorubicin encapsulation efficacy was calculated to be 92%. The effect of pH on release behaviors of rGO-g-PCL-b-PSEMA nanocarriers was investigated. The release rates at pH values of 7.4, 5.4 and 4 were about 52.1, 64.2 and 68.63 wt% after 775 min and at 37 °C. The release rate was improved at tumor simulated environment (42 °C and pH ≤ 5.4). The cytotoxic effects of nanosystems were appraised by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the results indicated that novel smart nanosystems were nontoxic to MCF-7 cells and can be applied as anticancer drug delivery systems.