Tumor-targeted delivery of siRNA remains a major barrier in fully realizing the therapeutic potential of RNA interference. While cell-penetrating peptides (CPP) are promising siRNA carrier candidates, they are universal internalizers that lack cell-type specificity. Herein, we design and screen a library of tandem tumor-targeting and cell-penetrating peptides that condense siRNA into stable nan...

BACKGROUND Basic cell-penetrating peptides are potential vectors for therapeutic molecules and display antimicrobial activity. The peptide-membrane contact is the first step of the sequential processes leading to peptide internalization and cell activity. However, the molecular mechanisms involved in peptide-membrane interaction are not well understood and are frequently controversial. Herein, ...

Tumor-specific tissue-penetrating peptides deliver drugs into extravascular tumor tissue by increasing tumor vascular permeability through interaction with neuropilin (NRP). Here, we report that a prototypic tumor-penetrating peptide iRGD (amino acid sequence: CRGDKGPDC) potently inhibits spontaneous metastasis in mice. The antimetastatic effect was mediated by the NRP-binding RXXK peptide moti...

INTRODUCTION The impermeability of biological membranes is a major obstacle in drug delivery; however, some peptides have transition capabilities of biomembranes. In recent decades, cell-penetrating peptides (CPPs) have been introduced as novel biocarriers that are able to translocate into the cells. CPPs are biologically potent tools for non-invasive cellular internalization of cargo molecules...

Abstract Staphylococcal nuclease domain-containing protein 1 (SND1) is a multifunctional oncoprotein overexpressed in breast cancer. Binding of metadherin (MTDH) to SND1 results the stabilization and important initiation progression Disruption such interaction potential therapeutic for SN1/2 domain was used as bait phage display screening identify 12-amino acid peptide 4-2. The activity 4-2 eva...

Cell penetrating peptides have demonstrated potential to facilitate the cellular delivery of therapeutic molecules. Here we develop a set of 50 cell penetrating peptide based formulations with potential to deliver small interfering RNAs intercellularly. The transfection efficacy of siRNA containing lipid-like nanoparticles decorated with different peptides was evaluated both in vitro and in viv...

Among gene delivery systems, peptide-based carriers have received significant attention because of their selectivity, biocompatibility, and biodegradability. Since cellular membranes function as a barrier toward exogenous molecules, cell-penetrating peptides (CPPs), which are usually cationic and/or amphiphilic, can serve efficient to deliver cargo into the cytosol. Here, we examined interactio...

In addition to endocytosis-mediated cellular uptake, hydrophilic cell-penetrating peptides are able to traverse biological membranes in a non-endocytic mode termed transduction, resulting in immediate bioavailability. Here we analysed structural requirements for the non-endocytic uptake mode of arginine-rich cell-penetrating peptides, by a combination of live-cell microscopy, molecular dynamics...

A homogeneous carbene-based palladium catalyst was conjugated to a cell-penetrating peptide, allowing intracellular delivery of catalytically active Pd complexes that demonstrated bioorthogonal activation of a profluorophore within prostate cancer cells.