Structural Engineering of Star Block Biodegradable Polymer Unimolecular Micelles for Drug Delivery in Cancer Cells

Abstract

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.

Size- and Shape-controlled Biodegradable Polymer Brushes Based on l-Amino Acid for Intracellular Drug Delivery and Deep-Tissue Penetration

“…From Figure 5d, it can be clearly depicted that the polymer brushes underwent enzymatic degradation to release more than 80% of the DOX in less than 24 h. In the case of PBS pH 7.4, the P-Tyr-PEG-DOX nanoparticles were stable and only 20% release of DOX was observed in 24 h, and this is attributed to the fact that PBS salt has effect on the nanoparticles. 57 P-Tyr-PEG2000-DOX polymer brush was also investigated for release studies, and data are shown in Figure S18. It is interesting to note that the rodlike polymer brush P-Tyr-PEG750-DOX exhibited much faster release of DOX compared to that of the spherical polymer brush P-Tyr-PEG5000-DOX.…”

“…In the control experiment, P-Tyr-PEG-DOX nanoparticles were incubated in PBS pH 7.4 to evaluate the stability in buffer at physiological conditions. From Figure d, it can be clearly depicted that the polymer brushes underwent enzymatic degradation to release more than 80% of the DOX in less than 24 h. In the case of PBS pH 7.4, the P-Tyr-PEG-DOX nanoparticles were stable and only 20% release of DOX was observed in 24 h, and this is attributed to the fact that PBS salt has effect on the nanoparticles . P-Tyr-PEG2000-DOX polymer brush was also investigated for release studies, and data are shown in Figure S18.…”

Precision Synthesis of Ultrastable Hydrophilic Metal Nanocluster Assemblies

“…The inner hydrophilic poly(acrylic acid) (PAA) polyelectrolyte segments were then synthesized via the hydrolysis of the hydrophobic PtBA segment to form the final β-CD-g-PAA-b-POEGA unimolecular micelle scaffold template, and PAA will provide nucleation sites to be the functional core of the template to coordinate with metal ions. 46,47 The rationally designed starlike polymers that are equipped with specific coordination sites with metal moieties, regular spherical morphology, and precisely controlled molecular weight offering unique advantages: they implement extensive and modular platforms as nanoreactors with stable, adaptable, and customized properties. As a proof of concept, the hydrophilic spherical Au nanocluster assemblies were synthesized via the nanoconfined in situ reduction of Au 3+ ions in the PAA segment of the scaffold template with the assistance of a hydrophilic thiolate ligand, 3-mercapto-1,2-propanediol (MP).…”

Macromolecular architectural effects on solution self-assembly of amphiphilic AB-type block copolymers

“…9). 164 Their results suggest that unimolecular micelles are promising materials for next-generation drug delivery systems, demonstrating enhanced drug-carrying capacity, reduced drug leakage, and increased cellular uptake compared with aggregated micelles. In summary, several advances in the design of star polymers, such as aromatic ring inclusion and the use of unimolecular micelles, have significantly enhanced their applicability and efficiency in drug delivery systems.…”