The present investigation reports the structural engineering
of
biodegradable star block polycaprolactone (PCL) to tailor-make aggregated
micelles and unimolecular micelles to study their effect on drug delivery
aspects in cancer cell lines. Fully PCL-based star block copolymers
were designed by varying the arm numbers from two to eight while keeping
the arm length constant throughout. Multifunctional initiators were
exploited for stepwise solvent-free melt ring-opening polymerization
of ε-caprolactone and γ-substituted caprolactone to construct
star block copolymers having a PCL hydrophobic core and a carboxylic
PCL hydrophilic shell, respectively. A higher arm number and a higher
degree of branching in star polymers facilitated the formation of
unimolecular micelles as opposed to the formation of conventional
multimicellar aggregates in lower arm analogues. The dense core of
the unimolecular micelles enabled them to load high amounts of the
anticancer drug doxorubicin (DOX, ∼12–15%) compared
to the aggregated micelles (∼3–4%). The star unimolecular
micelle completely degraded leading to 90% release of the loaded drug
upon treatment with the lysosomal esterase enzyme in vitro. The anticancer efficacies of these DOX-loaded unimolecular micelles
were tested in a breast cancer cell line (MCF-7), and their IC50 values were found to be much lower compared to those of
aggregated micelles. Time-dependent cellular uptake studies by confocal
microscopy revealed that unimolecular micelles were readily taken
up by the cells, and enhancement of the drug concentration was observed
at the intracellular level up to 36 h. The present work opens new
synthetic strategies for building a next-generation biodegradable
unimolecular micellar nanoplatform for drug delivery in cancer research.