Unimolecular Micelle for MLN8237 Delivery to Target AURKA-RalA Crosstalk for Ras-Driven Tumor Suppression in Mice Xenografts.

Targeting Aurora Kinase A (AURKA) to modulate RalA activation offers a promising strategy for tumor suppression in Ras-independent and Ras-dependent cancers. However, clinical use of the AURKA inhibitor MLN8237 (Alisertib) is limited by its hydrophobicity and poor water solubility. To overcome these limitations, here, we developed an enzyme-biodegradable unimolecular micelle (UMM) nanoparticle to deliver MLN8237 (NP) and evaluated its therapeutic efficacy in tumor xenograft models.

Tweaking Unimolecular Micellar Nanoarchitecture for Drug Delivery in Tumor Xenograft Mice Models.

Uncontrolled rapture of prodrug nano-formulation under physiological concentration gradient is a bottleneck in the effective delivery of anticancer drugs to solid tumors in vivo. The present investigation reports macromolecular nano-compartmentalization in single polymer chain micellar nanoparticle (or unimolecular micelle nanoparticle, UMNp) and demonstrates its therapeutic efficacies in pancreatic cancer xenograft mouse model. The UMNp is engineered in a six-arm enzymatic-biodegradable polycaprolactone star-polymer by employing a divergent approach using identical chemical constituents but varying the arms-lengths.

ROPISA Strategy for In-Situ Loading in Polypeptide Nanoparticles.

We report a ring-opening polymerization induced self-assembly (ROPISA) synthetic strategy for in-situ encapsulation of fluorescent dye molecules in poly(ʟ-serine) based polypeptide nano-assemblies and demonstrate their cellular bioimaging application. A bulky ʟ-serine N-carboxyanhydride monomer is tailor-made and polymerized using PEG-amine as hydrophilic macroinitiator in water at pH 8.5 to obtain polypeptide block copolymer as stable dispersions in the form of opalescent solutions.

Star-polymer unimolecular micelle nanoparticles to deliver a payload across the blood-brain barrier.

Nanocarrier-mediated therapeutic delivery to brain tissue is impeded by tightly controlled transportation across the blood-brain barrier (BBB). Herein, we report a well-defined core-shell star-shaped unimolecular micelle (star-UMM; a single polymer entity) as an efficient BBB-breaching nanoparticle for brain-specific administration of the fluorescent anticancer drug doxorubicin and mapping of brain tissues by the near-infrared biomarker IR780 in mice. The star-UMM was engineered by precisely programming the polymer topology having hydrophobic and hydrophilic polycaprolactone blocks and in-built with lysosomal enzyme-biodegradation stimuli to deliver the payloads at intracellular compartments.

Zwitterionic Strategy to Stabilize Self-Immolative Polymer Nanoarchitecture under Physiological pH for Drug Delivery In Vitro and In Vivo.

The major bottleneck in using polymer nanovectors for biomedical application, particularly those based on self-immolative poly(amino ester) (PAE), lies in their uncontrolled autodegradation at physiological pH before they can reach the intended target. Here, an elegant triblock-copolymer strategy is designed to stabilize the unstable PAE chains via zwitterionic interactions under physiological pH (pH 7.4) and precisely program their enzyme-responsive biodegradation specifically within the intracellular compartments, ensuring targeted delivery of the cargoes.

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

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.

Self-Reporting Polysaccharide Polymersome for Doxorubicin and Cisplatin Delivery to Live Cancer Cells.

We report self-reporting fluorescent polysaccharide polymersome nanoassemblies for enzyme-responsive intracellular delivery of two clinical anticancer drugs doxorubicin (DOX) and cisplatin to study the real-time drug-releasing aspects by fluorescent resonance energy transfer (FRET) bioimaging in live cancer cells. Fluorescent polymersomes were tailor-made by tagging an aggregation-induced emission (AIE) optical chromophore, tetraphenylethylene (TPE), and a plant-based vesicular directing hydrophobic unit through enzyme-biodegradable aliphatic ester chemical linkages in the polysaccharide dextran. The blue-luminescent polymersome self-assembled in water and exhibited excellent encapsulation capability for the red-luminescent anticancer drug DOX.