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.

Synthetic Strategy to Build High-Molecular-Weight Poly(L-tyrosine) and Its Unexplored β-Sheet Block Copolymer Nanoarchitectures.

Synthesis of high-molecular-weight polypeptides and their block copolymer macromolecular architectures from β-sheet-promoting L-amino acids is still an unresolved problem. Here, an elegant steric hindrance-assisted ring-opening polymerization (SHAROP) strategy is introduced to access β-sheet poly(L-tyrosine) having more than 250 units. The scope of the synthetic methodology is expanded to access unexplored poly(L-tyrosine)-based higher-order β-sheet block copolymer nanoassemblies.

ESIPT Nano-Emitter to Probe Lysosome Biogenesis in Live Cells.

Endosome-lysosome fusion and endo-lysosome fission-mediated lysosome biogenesis are crucial in regulating cellular health, and their dysregulation signifies disease. Tracking such intricate events with minimal disturbance remains elusive due to the scarcity of single-component synthetic probes capable of distinctly and simultaneously labeling both endosomes and lysosomes. Here, an amphiphilic π-conjugated imine probe is designed that forms micellar self-assemblies in water, called Nano-emitter, which distinctly and simultaneously labels endosomes and lysosomes upon monochromatic-wavelength excitation.