Facile PEGylation of Boltorn® H40 for pH-responsive drug carriers

A pH-responsive drug delivery system was developed through facile PEGylation of commercial aliphatic dendritic polyester Boltorn® H40 (H40) by forming the acetal linkages. Benefiting from its amphiphilic structure, the star copolymer (H40-star-MPEG) with a hydrophobic H40 core and many hydrophilic poly(ethylene glycol) (MPEG) arms was able to self-assemble into stable micelles in aqueous solution. Moreover, the size of self-assembled micelles could be easily tailored by only changing the grafting ratio of MPEG chains. The degradable behavior of H40-star-MPEG was measured by NMR technique under neutral and acidic deuterium aqueous medium. The experimental results showed that a fast hydrolysis of H40-star-MPEG occurred at a low pH solution, resulting from the cleavage of acetal linkages. The low cytotoxicity of H40-star-MPEG micelles was confirmed by cell evaluation. As a model anticancer drug, the hydrophobic drug doxorubicin (DOX) was encapsulated into the self-assembled H40-star-MPEG micelles. In an acidic environment, the drug release of DOX-loaded micelles was accelerated greatly. The DOX-loaded micelles could be internalized by the cancer cells efficiently, resulting in the effective inhibition to cancer cell proliferation. All of these results suggest that facile PEGylation of H40 with acetal linkages provides a promising pH-responsive drug carrier for cancer therapy.