Dataset Information

Peptide Spiders: Peptide-Polymer Conjugates to Traffic Nucleic Acids.

ABSTRACT: Therapeutic nucleic acids hold great promise for the treatment of genetic diseases, yet the delivery of this highly charged macromolecular drug remains a challenge in the field. Peptides are promising agents to mediate nucleic acid delivery because they can encode a biological function to overcome the trafficking barriers. Electrostatic nanocomplexes of nucleic acid and peptides can achieve effective delivery, but the balance between their stability and biological function must be finely tuned. In this work, we explore two peptide building blocks that have been studied in the literature: targeting ligands and intracellular trafficking peptides. We grafted these peptides on a polyethylene glycol (PEG) backbone with eight sites for substitution to create so-called "peptide spiders". These conjugates achieve stability via the well-known hydrophilic shielding effect of PEG. In addition, the coordination of peptide building blocks into multimers may create new biological properties, such as the well-known phenomena of increased binding avidity with multivalent ligands. In this work, we linked two trafficking peptides to the PEG backbone using either nonreducible or reducible chemistries and investigated the ability of these materials to carry silencing RNAs into mammalian cells. We then investigated these nanomaterials for their pharmacokinetic properties and silencing of undruggable targets in a mouse model of cancer. While reducible linkages were more potent at silencing in vitro, this effect was reversed when applied in the context of living animals. This work offers an insight into peptide-based delivery materials and investigates peptide-polymer linkages.

SUBMITTER: Kwon EJ

PROVIDER: S-EPMC7986012 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Bacterial adhesion and growth at the composite/adhesive/tooth interface remain the primary cause of dental composite restoration failure. Early colonizers, including Streptococcus mutans, play a critical role in the formation of dental caries by creating an environment that reduces the adhesive's integrity. Subsequently, other bacterial species, biofilm formation, and lactic acid from S. mutans demineralize the adjoining tooth. Because of their broad spectrum of antibacterial activity and low risk for antibiotic resistance, antimicrobial peptides (AMPs) have received significant attention to prevent bacterial biofilms. Harnessing the potential of AMPs is still very limited in dentistry-a few studies have explored peptide-enabled antimicrobial adhesive copolymer systems using mainly nonspecific adsorption. In the current investigation, to avoid limitations from nonspecific adsorption and to prevent potential peptide leakage out of the resin, we conjugated an AMP with a commonly used monomer for dental adhesive formulation. To tailor the flexibility between the peptide and the resin material, we designed two different spacer domains. The spacer-integrated antimicrobial peptides were conjugated to methacrylate (MA), and the resulting MA-AMP monomers were next copolymerized into dental adhesives as AMP-polymer conjugates. The resulting bioactivity of the polymethacrylate-based AMP conjugated matrix activity was investigated. The antimicrobial peptide conjugated to the resin matrix demonstrated significant antimicrobial activity against S. mutans. Secondary structure analyses of conjugated peptides were applied to understand the activity differential. When mechanical properties of the adhesive system were investigated with respect to AMP and cross-linking concentration, resulting AMP-polymer conjugates maintained higher compressive moduli compared to hydrogel analogues including polyHEMA. Overall, our result provides a robust approach to develop a fine-tuned bioenabled peptide adhesive system with improved mechanical properties and antimicrobial activity. The results of this study represent a critical step toward the development of peptide-conjugated dentin adhesives for treatment of secondary caries and the enhanced durability of dental composite restorations.

Dataset Information

Peptide Spiders: Peptide-Polymer Conjugates to Traffic Nucleic Acids.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets