Sticky Patches on Lipid Nanoparticles Enable the Selective Targeting and Killing of Untargetable Cancer Cells.

Effective targeting by uniformly functionalized nanoparticles is limited to cancer cells expressing at least two copies of targeted receptors per nanoparticle footprint (approximately ≥2 × 10(5) receptor copies per cell); such a receptor density supports the required multivalent interaction between the neighboring receptors and the ligands from a single nanoparticle. To enable selective targeting below this receptor density, ligands on the surface of lipid vesicles were displayed in clusters that were designed to form at the acidic pH of the tumor interstitium. Vesicles with clustered HER2-targeting peptides within such sticky patches (sticky vesicles) were compared to uniformly functionalized vesicles.

Masking and triggered unmasking of targeting ligands on liposomal chemotherapy selectively suppress tumor growth in vivo.

We investigated the feasibility and efficacy of a drug delivery strategy to vascularized cancer that combines targeting selectivity with high uptake by targeted cells and high bioexposure of cells to delivered chemotherapeutics. Targeted lipid vesicles composed of pH responsive membranes were designed to reversibly form phase-separated lipid domains, which are utilized to tune the vesicle's apparent functionality and permeability. During circulation, vesicles mask functional ligands and stably retain their contents.

Solid-phase synthesis of short α-helices stabilized by the hydrogen bond surrogate approach.

Stabilized α-helices and nonpeptidic helix mimetics have emerged as powerful molecular scaffolds for the discovery of protein-protein interaction inhibitors. Protein-protein interactions often involve large contact areas, which are often difficult for small molecules to target with high specificity. The hypothesis behind the design of stabilized helices and helix mimetics is that these medium-sized molecules may pursue their targets with higher specificity because of a larger number of contacts.

Morphology controlled growth of chitosan-bound microtubes and a study of their biocompatibility and antibacterial activity.

Self-assembled peptide microtubes are fabricated with the biopolymer chitosan. The microtubes are covalently attached to chitosan and the morphology of the chitosan assembled on the surface of the microtubes can be tuned by altering the pH of the growth solution. Cytotoxicity studies in the presence of mouse embryonic fibroblasts indicate that the chitosan-bound microtubes are highly biocompatible and the cells are able to survive and proliferate at a similar rate to the control.