Comparison between novel star-like redox-sensitive amphiphilic block copolymer and its linear counterpart copolymer as nanocarriers for doxorubicin

Abstract

Linear and star-like redox-sensitive amphiphilic block copolymers have been studied as anticancer drug delivery systems. However, few reports directly compared the properties of those two structures especially when they are used as nanocarriers for antitumor drugs. To address this, a novel star-like copolymer and its linear counterpart were synthesized with a hydrophobic/redox-responsive/hydrophilic structure. The overall molecular weight of the star-shaped copolymer was nearly equal to that of the linear counterpart. The star-like micelles exhibit size of 90 nm, which was smaller than that of linear copolymers (151.6 nm) and critical micelle concentration of 1 mg/L, which was lower than that of the linear micelles (8.9 mg/L). The disassembly behaviors and the redox-sensitivity of the nanoparticles to reductive stimuli of glutathione was evaluated from the changes of the micellar size and morphology. Furthermore, doxorubicin was physically loaded into the hydrophobic part of the copolymers. The drug-loading capacities in the star-like and linear micelles were 15.94 and 7.53 wt%, respectively. Drug release studies carried out at two different glutathione concentrations. A cytotoxicity study of the micelles was performed by MTT assay. The prepared star copolymer showed no significant toxicity against HDF cells while enhanced cytotoxicity of the DOX-loaded micelles against MCF-7 cells was observed. Therefore, developing sucrose-PCL-SS-PEG copolymer reported in this paper as an effective reduction-responsive carrier with excellent properties and cell biocompatibility is promising for the efficient intracellular delivery of hydrophobic chemotherapeutic drugs. This work also indicates that modification of the nanocarrier structure is a potential strategy for optimizing drug delivery.