Peptide‐Directed Self‐Assembly of Functionalized Polymeric Nanoparticles Part I: Design and Self‐Assembly of Peptide–Copolymer Conjugates into Nanoparticle Fibers and 3D Scaffolds

Abstract

A robust self-assembly of nanoparticles into fibers and 3D scaffolds is designed and fabricated by functionalizing a RAFT-polymerized amphiphilic triblock copolymer with designer ionic complementary peptides so that the assembled core-shell polymeric nanoparticles are directed by peptide assembly into continuous "nanoparticle fibers," ultimately leading to 3D fiber scaffolds. The assembled nanostructure is confirmed by FESEM and optical microscopy. The assembly is not hindered when a protein (insulin) is incorporated within the nanoparticles as an active ingredient. MTS cytotoxicity tests on SW-620 cell lines show that the peptides, copolymers, and peptide-copolymer conjugates are biocompatible. The methodology of self-assembled nanoparticle fibers and 3D scaffolds is intended to combine the advantages of a flexible hydrogel scaffold with the versatility of controlled release nanoparticles to offer unprecedented ability to incorporate desired drug(s) within a self-assembled scaffold system with individual control over the release of each drug.

Weak bond-based injectable and stimuli responsive hydrogels for biomedical applications

“…67–70 This strategy is receiving more attention for the construction of supramolecular hydrogels for controlled drug or cell delivery in tissue regeneration. 71–79 The hydrogels formed by electrostatic interactions from polyelectrolytes possess several advantages: (1) cationic and anionic polyelectrolytes are typically water soluble, so they alleviate the use of organic solvent during gel construction; (2) ionic interaction is highly specific and efficient to accomplish quick gelation; (3) payloads, such as bioactive proteins, can better retain their molecular configuration and preserve their bioactivities in aqueous environments; and (4) electrostatic interactions are sensitive to polyelectrolyte concentration and medium conditions, including pH, ionic strength and temperature, to tune the performance for specific applications. 78, 80 In this section, we will discuss ionic interaction-based hydrogels using engineered ionic complementary peptides, synthetic polyelectrolytes and natural polyelectrolytes.…”

A novel near-infrared fluorescent probe for sensitive detection of β-galactosidase in living cells

“…The MTS assay was performed with human diploid fibroblast (HDF) cells (ATCC), as previously described[18]. Briefly, the cells were plated at a density of 5000 cells per well on a 96-well cell culture plate and incubated at 37°C in a 5% CO 2 incubator overnight.…”

Peptide-Directed Self-Assembly of Functionalized Polymeric Nanoparticles. Part II: Effects of Nanoparticle Composition on Assembly Behavior and Multiple Drug Loading Ability

“…All reagents for peptide synthesis were purchased from AAPPTec LLC (Louisville, KY) and used as received. Synthesis of ionic complementary peptides (P1: H 2 N‐TTTT‐AEAEAEAE‐amide and P2: H 2 N‐TTTT‐AKAKAKAK‐amide) was described in previous work . 1‐Vinyl‐2‐pyrrolidinone (VP) (≥99%), 2‐hydroxyethyl methacrylate (HEMA) (97%), methyl methacrylate (MMA) (99%), 1,4‐dioxane (99 + %), 2,2′‐azobisisobutyronitrile (AIBN) (98%), dimethyl formamide (DMF, 99.9%), phosphate buffered saline (Biotech) and model drugs of nitrofurazone (NF), 4′,5′‐dibromofluorescein (DBF), fluorescein (FL), and cell adhesion peptide (RGDS) were purchased from Sigma–Aldrich.…”

“…A detailed peptide synthesis for P1 (H 2 N‐TTTT‐AEAEAEAE‐amide) and P2 (H 2 N‐TTTT‐AKAKAKAK‐amide), characterization by MALDI‐TOF MS (Microflex LRF, BrukerDaltonics, Billerica, USA) and 1 H NMR (Varian Unity INOVA 400 MHz, McKinley Scientific, Sparta, NJ, USA), and the self‐assembly behavior of the designer peptides were already reported in previous study and Supporting Information …”

“…In Part I of this series we demonstrated a new approach to fabricate tissue scaffolding, prepared by peptide‐directed self‐assembly of polymeric nanoparticles into fibers and 3D scaffolds, to address these limitations . That paper described the synthesis and assembly of the nanoparticle fiber scaffolds, demonstrated the ability to contain low and high molecular weight model drugs, and proved the incorporation and controlled release of insulin from the peptide conjugate nanoparticles and the assembled scaffold.…”