R9 peptide

Oligo-basic amino acids have been extensively studied in molecular biology and pharmacology, but the inhibitory activity on nicotinic acetylcholine receptors (nAChRs) was unknown. In this study, the inhibitory activity of 8 oligopeptides, including both basic and acidic amino acids, was evaluated on 9 nAChR subtypes by a two-electrode voltage clamp (TEVC). Among them, the oligo-lysine K9, K12, d-K9, d-K9F, and oligo-arginine R9 showed nanomolar inhibitory activity on various nAChRs, especially for α7 and α9α10 nAChRs...

In this study, we designed a series of hybrid peptides based on pep5-TAT (P-05), comprising antitumor segment (pep5), endosomal escape segment ((LLHH)3 ) and cell penetrating/membrane disrupting segment (TAT, R9 , sC182 ). These peptides exhibited remarkable antitumor activity towards tumor cells (HepG2, A549). Among them, the IC50 values of peptide P-09 were 4.0 and 4.8 times lower than those of P-05 in HepG2 and A549 cells, respectively. It was proved that P-09 could enter tumor cells through endocytosis and direct penetration and induce the apoptosis and necrosis...

Human epidermal growth factor receptor 2 (HER2) protein overexpression is found in ~30% of invasive breast carcinomas and in a high proportion of noninvasive ductal carcinomas in situ. Targeted cancer therapy is based on monoclonal antibodies and kinase inhibitors and reflects a new era of cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. Furthermore, there are many disadvantages with the current anti-HER2 drug, including drug resistance and adverse effects...

Chitosan and its derivatives have been extensively utilized in gene delivery applications because of their low toxicity and positively charged characteristics. However, their low solubility under physiological conditions often limits their application. Glycol chitosan (GC) is a derivative of chitosan that exhibits excellent solubility in physiological buffer solutions. However, it lacks the positive characteristics of a gene carrier. Thus, we hypothesized that the introduction of oligoarginine peptide to GC could improve the formation of complexes with siRNA, resulting in enhanced uptake by cells and increased transfection efficiency in vitro...

Extracellular vesicles (EVs) are cell-to-cell communication tools. Migrasomes are recently discovered microscale EVs formed at the rear ends of migrating cells, and thus are suggested to be involved in communicating with neighboring cells. In cell culture, peptide scaffolds on substrates have been used to demonstrate cellular function for regenerative medicine. In this study, we evaluated peptide scaffolds, including cell penetrating, virus fusion, and integrin-binding peptides, for their potential to enable the formation of migrasome-like vesicles...

A fusion protein comprising an antibody and a cationic peptide, such as arginine-9 (R9), is a candidate molecule for efficient and cell-specific delivery of siRNA into cells in order to reduce the side effects of nucleic acid drugs. However, their expression in bacterial hosts, required for their development, often fails, impeding research progress. In this study, we separately prepared anti-EGFR nanobodies with the K-tag sequence MRHKGS at the C-terminus and R9 with the Q-tag sequence LLQG at the N-terminus, and enzymatically ligated them in vitro by microbial transglutaminase to generate Nanobody-R9, which is not expressed as a fused protein in E...

Cell-penetrating peptides (CPPs) have been regarded as potential drug carriers for cancer therapy. However, most well-studied CPPs fail to deliver exogenous drugs efficiently and selectively. In this study, a tumour-targeted CPP with high efficiency derived from heparin-binding domain (HBD) of Midkine (named HMD) was discovered. HMD exhibited higher delivery efficiency than classic CPPs (TAT and R9) and manifested selectivity in tumour cells. Normally, the positive charge is the key factor for the transmembrane activity of CPPs such as TAT and R9...

Treatment of glioma remains a critical challenge worldwide, since the therapeutic effect is greatly hindered by poor transportation across the blood brain barrier (BBB) and low penetration into tumor cells. In this study, a peptide-conjugated nano-delivery system was explored for the purpose of glioma therapy. A peptide-decorated copolymer was used to prepare nanoparticles (NPs) by a solvent evaporation method. The particle size was in the range of 160.9 ± 3.3-173.5 ± 3.6 nm with monodistribution, and the zeta potentials ranged from -18...

Small interfering RNA (siRNA)-based drugs have shown tremendous potential to date in cancer gene therapy. Despite the considerable efforts in siRNA design and manufacturing, unsatisfactory delivery systems persist as a limitation for the application of siRNA-based drugs. In this work, the cholesterol, cell-penetrating peptide conjugate cRGD (R8-cRGD), and polyethylene glycol (PEG) were introduced into low-molecular-weight polyethyleneimine (LMW PEI) to form cRGD-R9-cholesterol-PEI-PEG (RRCPP) nanoparticles with specific targeting and highly penetrating abilities...

In brain-targeted delivery, the transport of drugs or genes across the blood-brain barrier (BBB) is a major obstacle. Recent reports found that focused ultrasound (FUS) with microbubbles enables transient BBB opening and improvement of drug or gene delivery. We previously developed nano-sized bubbles (NBs), which were prepared based on polyethylene glycol (PEG)-modified liposomes containing echo-contrast gas, and showed that our NBs with FUS could also induce BBB opening. The aim of this study was to enhance the efficiency of delivery of pDNA into neuronal cells following transportation across the BBB using neuron-binding peptides...

Background: Gene therapy has emerged as a new strategy for cancer therapy. As an alternative nucleic acid material, messenger ribonucleic acid (mRNA) is being increasingly utilized in cancer gene therapy. However, unfulfilled requirements and a lack of ideal mRNA delivery vectors persist. Methods: We developed an advanced mRNA delivery system, DMP-039, by fusing a cell-penetrating peptide, cRGD-R9, and a cationic nano-sized DMP backbone together. The DMP gene vector backbone was synthesized by the self-assembly of DOTAP lipid and mPEG-PCL polymer...

Cerebral ischemia, a common cerebrovascular disease, is characterized by functional deficits and apoptotic cell death. Autophagy, a type of programmed cell death, plays critical roles in controlling neuronal damage and metabolic homeostasis, and has been inextricably linked to cerebral ischemia. We previously identified a short peptide aptamer from collapsin response mediator protein 2 (CRMP2), designated the Ca2+ channel-binding domain 3 (CBD3) peptide, that conferred protection against excitotoxicity and traumatic brain injury...

BACKGROUND: A significant challenge in cancer therapy is to maximize the therapeutic efficacy and minimize the side effects. In the past decade, a lot of nanoparticles have been used as the carriers for efficient drug delivery. METHODS AND RESULTS: This study was to prepare R9 modified with 125 I-labeled cRGD and ce6 which self-assembled with miR-139-5p to form nanoparticles (Ce6-R9-125 I-RGD-MNPs), and to further take advantage of the enhanced permeability and retention (EPR) effect of radiolabeled nanoparticles to realize the integration of tumor diagnosis and treatment...

Gene therapy provides a promising treatment for glioblastoma multiforme, which mainly depends on two key aspects, crossing the blood brain barrier (BBB) effectively and transfecting target cells selectively. In this work, we reported a series of peptide-based vectors for transfecting glioma cells specifically consisting of several functional segments including a cell-penetrating peptide, targeting segment substance P (SP), an endosomal escape segment, a PEG linker and a stearyl moiety. The conformations and DNA-loading capacities of peptide vectors and the self-assembly behaviors of peptide/pGL3 complexes were characterized...

MicroRNAs (miRNAs) are emerging as a novel class of molecular targets and therapeutics to control gene expression for tissue repair and regeneration. However, a safe and effective transfection of miRNAs to cells has been a major barrier to their applications. In this work, a multifunctional polyplex micelle named PPP-RGI was developed as a non-viral gene vector for the efficient transfection of miR-218 (an osteogenic miRNA regulator) to bone marrow-derived mesenchymal stem cells (BMSCs) for accelerated osteogenic differentiation...

OBJECTIVE: To develop a nano-delivery system for targeted delivery of miR-16/polypeptide for enhancing cisplatin sensitivity of ovarian cancer. OBJECTIVE: R9-SS-R9 and cRGD-R9-SS-R9 peptides were synthesized and self-assembled with miR-16 molecules to form a nano-delivery system. The stability, particle size, potential and morphology of the nanoparticles were determined by agarose gel electrophoresis, particle size potentiometer and transmission electron microscopy...

Purpose: Uveitis is an ocular inflammation that can affect individuals of all ages and is a major cause of blindness. We have tested the therapeutic efficacy of a cell penetrating peptide from the kinase inhibitory region of suppressor of cytokine signaling 1, denoted as R9-SOCS1-KIR. Methods: We stimulated J774A.1 cells with lipopolysaccharide (LPS) in the presence of R9-SOCS1-KIR or its inactive control peptide. Effect on inflammatory pathways was followed by the nuclear translocation of nuclear factor κB p65 subunit and phosphorylated-p38...

Androgen receptor (AR) and/or its constitutively active splicing variants (AR‑Vs), such as AR‑V7 and ARv567es, is required for prostate cancer cell growth and survival, and cancer progression. Proliferating cell nuclear antigen (PCNA) is preferentially overexpressed in all cancers and executes its functions through interaction with numerous partner proteins. The aim of the present study was to investigate the potential role of PCNA in the regulation of AR activity. An identical consensus sequence of the PCNA‑interacting protein‑box (PIP‑box) was identified at the N‑terminus of human, mouse and rat AR proteins...

Effective sublingual peptide immunization requires overcoming challenges of both delivery and immunogenicity. Mucosal adjuvants, such as cyclic-dinucleotides (CDN), can promote sublingual immune responses but must be codelivered with the antigen to the epithelium for maximum effect. We designed peptide-polymer nanofibers (PEG-Q11) displaying nona-arginine (R9) at a high density to promote complexation with CDNs via bidentate hydrogen-bonding with arginine side chains. We coassembled PEG-Q11 and PEG-Q11R9 peptides to titrate the concentration of R9 within nanofibers...

A lysosome-targeting ratiometric fluorescent nanoprobe based on cell-penetrating peptides (CPPs) and quantum dots (QDs) has been developed for monitoring pH fluctuation in living cells. The as-prepared nanoprobe is constructed by Rhodamine B labeled R9 RGD CPPs as H+ response unit and the red fluorescent QDs as reference unit to achieve ratiometric pH measurement. With the help of RhB-R9 RGD CPPs, the nanoprobe efficiently stains lysosomes and enables discernment of lysosomal pH fluctuation in cells treated with different pH buffers and drug stimulation...