Quantitatively Fine-Tuning the Physicochemical and Biological Properties of Peptidic Polymers through Monodisperse PEGylation

Abstract

In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it is challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation strategies, including backbone PEGylation, side-chain PEGylation, and highly branched PEGylation, have been developed. In a comparative fashion, the impact of PEGylation strategies and monodisperse PEG sizes on the physicochemical and biological properties, including lipophilicity, thermosensitivity, biocompatibility, plasma stability, and drug delivery capability, of peptidic polymers has been quantitatively studied. It was found that the physicochemical and biological properties of PEGylated peptidic polymers can be quantitatively fine-tuned and accurately predicted through these monodisperse PEGylation strategies. After the comparative study, a side-chain monodisperse PEGylated peptidic polymer was chosen as fluorine-19 magnetic resonance and fluorescence dual-imaging traceable drug delivery vehicle. Our study may not only promote the transformation of PEGylation from an empirical technology to a quantitative science but also shed light on the rational design of PEGylated biomaterials and pharmaceutics.

19F MRI Nanotheranostics for Cancer Management: Progress and Prospects

“…Other reduction‐responsive nanoprobes, such as branched fluorinated glycopolymers [119] and amino‐activatable nanocomposites, [120] exhibited reductive microenvironment‐enhanced 19 F MRI performance and were used for targeted diagnosis of breast cancer and sensitive imaging of HCC, respectively. Similarly, a wide variety of thermosensitive fluorinated materials, including peptidized fluorine‐containing PEG combs, [121] monodisperse peptidic polymers with different PEGylation strategies and PEG sizes, [122] amphiphilic copolymer nanogels, [123] and PFPE‐based comb‐like poly(2‐oxazoline)s, [124] have been designed and used for thermo‐activated 19 F MRI‐associated cancer management. On this basis, multi‐stimulus‐responsive nanosystems have also been explored.…”

Stapling of Peptides Potentiates the Antibiotic Treatment of Acinetobacter baumannii In Vivo

“…However, many peptides have been described as losing activity under physiological conditions as they are prone to proteolytic degradation, which limits their use to topical applications [ 18 , 20 , 21 ]. Several attempts have been made to increase the stability of CAMPs, such as D-amino acid substitution, PEGylating, lipidation, macrocyclization and peptide stapling [ 21 , 22 , 23 , 24 , 25 ]. The latter is a technique that introduces an intramolecular side chain-to-side crosslink to increase α-helicity and thereby proteolytic stability [ 23 , 25 , 26 ].…”

Drug Development through Modification of Small Molecular Drugs with Monodisperse Poly(ethylene glycol)s

“…With the macrocyclic sulfates as ideal building blocks, a series of M-PEGs, including nonfunctionalized M-PEGs, monofunctionalized M-PEGs, hetero-dual-functionalized M-PEGs, homo-dual-functionalized M-PEGs, and highly branched M-PEGs, have been synthesized with a minimal number of synthetic steps, high efficiency, and low cost. Since the novel strategy to synthesize M-PEGs was established, M-PEGs have been employed to develop novel imaging agents, stimuli-responsive biomaterials, drug delivery systems, and SMDs …”