Dopamine-modified poly(ε-caprolactone) micelles for pH controlled delivery of bortezomib.

Poly(ethylene glycol)-poly(ε-caprolactone) (PEG-b-PCL) micelles have been widely used as drug delivery vehicles for cancer therapies. Because of the lack of functional groups, the use of PEG-b-PCL in drug delivery system is greatly limited and structural modifications is needed. In this work, chemical modification at the terminus of PEG-b-PCL was performed via the "grafting from" polymerization method. A poly(dopamine methyl acrylamide) segment was introduced containing multiple catechol groups, which could attach bortezomib (BTZ) to the chain of the polymer through the formation of a pH-sensitive borate bond. This method greatly enhanced the loading capacity of BTZ into the micelles. Additionally, the controlled release of BTZ in response to the acidic environment of a tumor was realized. High loading capacity, stimuli-responsiveness, biodegradability, and compatibility were integrated in the PEG-b-PCL-based system. In vitro and in vivo studies demonstrated that superior tumor inhibition without obvious side effects can be achieved by the BTZ-loaded PEG-b-PCL-b-PDMA micelles. [ABSTRACT FROM AUTHOR]