Self-assembled PEGylated amphiphilic polypeptides for gene transfection

Abstract

In the present study, three biodegradable block copolymers composed of a poly(ethylene glycole) block and a copolypeptide block with varying compositions of cationic L-lysine (L-Lys) and hydrophobic benzyl-L-glutamate (Bzl-L-Glu) were...

Efficient Gene Delivery of Tailored Amphiphilic Polypeptides by Polyplex Surfing

“…In contrast, hydrophobic cationic polypeptide systems previously investigated by our group showed much lower transfection efficiency compared to the commercial control LPEI. 5 Thus, the best performing P3 polypeptide in this study is a promising candidate for gene delivery not only because of its simpler synthesis and higher synthetic variability but also due to its substantially better performance in comparison to LPEI.…”

“…The respective amount of BocDAB or HexA [mol % and degree of polymerization (DP)] in each compound, summarized in Table , was calculated by area correlation of the characteristic signals in the 1 H NMR spectra using the Peak Analyzer of Origin 9.1.0G (OriginLab Corporation), according to a procedure published elsewhere (Figure S8). In addition, the DP of PBLG was presumed as total DP of PP1 – PP4 and P5 . The theoretical molar mass ( M n,theo ) was calculated by adding the molar mass of all 96 units and of the initiator.…”

“…Synthetic polypeptide-based materials are analogues to functional, e.g., antimicrobial, peptides 1 and a powerful tool often used in drug 2,3 and gene delivery 4,5 and controlled protein release. 6 In particular, the development of suitable vectors for gene delivery, offering versatile possibilities for the treatment of diseases with genetic origin or for vaccination, has attracted increasing attention.…”

ROS-Responsive Selenopolypeptide Micelles: Preparation, Characterization, and Controlled Drug Release

“…Polypeptides are synthetic analogues of natural proteins with excellent biocompatibility and biodegradability and have shown wide utilities in the biomedical field. Amphiphilic, polypeptide-based diblock copolymers, such as poly­(ethylene glycol) (PEG)- block -polypeptides, can self-assemble into nanostructures that serve as promising vehicles for drug delivery. − The versatile side chain design of synthetic polypeptides allows facile incorporation of trigger-responsive moieties, which enable controlled release of encapsulated cargos from polypeptide-based nanocarriers. − Additionally, polypeptides adopt unique secondary structures, such as α-helix and β-sheet, which are also closely associated with the structure and function of polypeptide-based nanovehicles. − Sulfur-containing polypeptides, including those with disulfide and thioether side chains, are widely studied as the building blocks of polypeptide-based nanoassemblies, mainly due to their redox responsiveness that triggers the structural change of the nanocarriers and subsequently promotes the release of cargos. − Specifically, thioethers on polypeptide side chains can be oxidized to sulfoxide or sulfone groups by reactive oxygen species (ROS), resulting in significant changes in the side-chain polarity, hydrophilicity, and even the backbone secondary structure . As a result, amphiphilic block copolymer assemblies based on thioether-containing polypeptides can experience ROS-responsive structural change and subsequently lead to the release of the encapsulated payloads. − Nevertheless, oxidation of thioether usually requires a relatively high concentration of ROS (typically 10% H 2 O 2 , v/v), which greatly limits its application in the in vivo environment.…”

Versatile fully-substituted triazole-functionalized polypeptides with a stable α-helical conformation for gene delivery

“…[1][2][3] Synthetic polypeptides, as the analogues of natural proteins, are emerging biomimetic materials owing to their ability to not only form a stable α-helix, but also achieve structural diversity via introducing versatile unnatural components. [4][5][6][7] To date, synthetic polypeptides have been extensively used in cell penetration, 8,9 drug/gene delivery, [10][11][12][13][14] antibacterial agents [15][16][17][18][19] and tissue engineering. 20,21 Ring opening polymerization (ROP) of an N-carboxyanhydride (NCA) monomer has been developed as a facile method to prepare high molecular weight and multi-functional polypeptides with α-helical structures.…”