Self-Assembly Mediated Platform for Rapid and Facile Preparation of Peptide-Functionalized Nanoparticles with High Stability

We recently reported a two-component self-assembling system, where the core of nanoparticles (NPs) was first assembled by a simple triskelion Fmoc-conjugate (FTAEA) and then stabilized by an oligopeptide, Fmoc-FY. Here we showed that the two-component NPs were stable upon heating, incubation, and dilution. We expanded the oligopeptides suitable for stabilization and therefore allowed peptides to serve the dual role of stabilization and functionalization. Twelve molecules were systematically designed and tested to define the design criteria of oligopeptide stabilizers, which are summarized as follows: 1) carrying Fmoc headgroup to match with the aromatic groups on the NP core, 2) restricting the first amino acid to those with self-interacting side chains, and 3) the net charge of the hydrophilic oligopeptide sequence being negative. To validate these criteria, we designed two bioactive peptides, Fmoc-FC and Fmoc-FRGD, which were demonstrated to be capable of stabilizing FTAEA NPs. The bioactivity of the peptide was illustrated with Nile red-loaded Fmoc-FRGD stabilized NPs of around 70 nm in diameters. These NPs were differentially internalized by MDA-MB-435 human cancer cells compared to NPs stabilized with the scrambled sequence, Fmoc-FRDG. Our results here showed that the stepwise aromatic-driven self-assembly provided a facile and versatile approach to construct functionalized and bioactive NPs, which are expected to find applications in drug delivery and bioimaging

Self-Assembly Mediated Platform for Rapid and Facile Preparation of Peptide-Functionalized Nanoparticles with High Stability

We recently reported a two-component self-assembling system, where the core of nanoparticles (NPs) was first assembled by a simple triskelion Fmoc-conjugate (FTAEA) and then stabilized by an oligopeptide, Fmoc-FY. Here we showed that the two-component NPs were stable upon heating, incubation, and dilution. We expanded the oligopeptides suitable for stabilization and therefore allowed peptides to serve the dual role of stabilization and functionalization. Twelve molecules were systematically designed and tested to define the design criteria of oligopeptide stabilizers, which are summarized as follows: 1) carrying Fmoc headgroup to match with the aromatic groups on the NP core, 2) restricting the first amino acid to those with self-interacting side chains, and 3) the net charge of the hydrophilic oligopeptide sequence being negative. To validate these criteria, we designed two bioactive peptides, Fmoc-FC and Fmoc-FRGD, which were demonstrated to be capable of stabilizing FTAEA NPs. The bioactivity of the peptide was illustrated with Nile red-loaded Fmoc-FRGD stabilized NPs of around 70 nm in diameters. These NPs were differentially internalized by MDA-MB-435 human cancer cells compared to NPs stabilized with the scrambled sequence, Fmoc-FRDG. Our results here showed that the stepwise aromatic-driven self-assembly provided a facile and versatile approach to construct functionalized and bioactive NPs, which are expected to find applications in drug delivery and bioimaging

One-Step “Click” Method for Generating Vinyl Sulfone Groups on Hydroxyl-Containing Water-Soluble Polymers

One-Step “Click” Method for Generating Vinyl Sulfone Groups on Hydroxyl-Containing Water-Soluble Polymer

Formulation of In Situ Chemically Cross-Linked Hydrogel Depots for Protein Release: From the Blob Model Perspective

The fast release rate and the undesirable covalent binding are two major problems often encountered in formulating in situ chemically cross-linked hydrogel as protein release depot, particularly when prolonged release over months is desirable. In this study, we applied the De Gennes’ blob theory to analyze and tackle these two problems using a vinylsulfone-thiol (VS-SH) reaction based in situ hydrogel system. We showed that the simple scaling relation ξ_b ≈ <i>R</i>_g(<i>c</i>/<i>c</i>*)^{−<i>v</i>/(3<i>v</i>−1)} is applicable to the in situ hydrogel and the mesh size estimated from the precursor polymer parameters is a reasonable match to experimental results. On the other hand, as predicted by the theory and confirmed by experiments, the drug diffusion within hydrogel depends mainly on polymer concentration but not the degree of modification (DM). The covalent binding was found to be caused by the mismatch of location between the reactive groups and the entanglement points. The mismatch and, thus, the protein binding were minimized by increasing the DM and concentration of the SH polymer relative to the VS polymer, as predicted by theory. Using these principles, an in situ hydrogel system for the controlled release of an antiangiogenic antibody therapeutics bevacizumab for 3 months was developed

Structural Mimics of Viruses Through Peptide/DNA Co-Assembly

A synthetic mimic of viral structure has been constructed by the synergistic co-assembly of a 16-amino acid peptide and plasmid DNA. The rational design of this short peptide, including segments for binding DNA and forming β-sheet, is inspired by viral capsid protein. The resulting nanostructures, which we term nanococoons, appear as ellipsoids of virus-like dimension (65 × 47 nm) and display repeating stripes of ∼4 nm wide. We propose that the co-assembly process involves DNA as a template to assist the organization of peptide strands by electrostatic interaction, while the bilayer β-sheets and their lateral association stabilize the peptide “capsid” and organize the DNA within. The hierarchy affords an extremely stable structure, protecting peptide and DNA against enzymatic digestion. It opens a new and facile avenue to fabricate viral alternatives with diverse functions

Stochastic Modeling of Degradation Behavior of Hydrogels

We describe here a theoretical framework to model the bulk degradation of hydrogels, which are prepared by chemical cross-linking of pendant functional groups on long polymer chains. The random order of the cleavage of degradable bonds was described by stochastic Monte Carlo simulation. The events of bond cleavage were related to the macroscopic changes of hydrogel by the Bray–Merrill equation. Next, the time for the gel to disintegrate was predicted by considering the relation between the recursive nature in breaking the cross-link nodes and gel-to-sol transition. To start the simulation, initial network properties including the number of active functional groups on the polymer chain and the concentration of polymer were employed as input, and the kinetic rate constant of bond cleavage was fitted for the swelling profile. No fitting parameter was required for disintegration time. A series of degradable hydrogels composed of dextran modified by methacrylate and thiol groups were synthesized and examined experimentally to verify the models. The measured mass swelling ratio and gel disintegration time matched with the model predictions. Correlation was found between the initial hydrogel network properties and the profiles of degradation. The results also revealed that degradable hydrogels with a wide range of disintegration times (from 3 days to 1 month) could be prepared by manipulating the hydrogel formulation (for example, polymer concentration and degree of modification) without altering the chemistry of the cleavable bond