Protein-Resistant Biodegradable Amphiphilic Graft Copolymer Vesicles as Protein Carriers

Abstract

The protein adsorption and self-assembly behavior of biocompatible graft copolymer, poly(lactide-co-diazidomethyl trimethylene carbonate)-g-poly(ethylene glycol) [P(LA-co-DAC)-g-PEG], were systematically studied. The graft copolymers showed enhanced resistance to non-specific protein adsorption compared with their block copolymer counterparts, indicative of the increased effect of PEG density beyond PEG length. Diverse nanostructures including vesicles can be assembled from the amphiphilic graft copolymers with well-defined nano-sizes. Hemoglobin (Hb), as a model protein, can be entrapped in the formed vesicles and keep the gas-binding capacity. The reduced release rate of Hb from graft copolymer vesicles indicated the relatively stable membrane packing compared with block copolymer counterpart.

Compact Vesicles Self-Assembled from Binary Graft Copolymers with High Hydrophilic Fraction for Potential Drug/Protein Delivery

“…As we know, the molecular architecture of copolymers is an important factor to control the morphology and surface functionality of the assemblies. , On the other hand, the most abundant lipid found in cell membranes is the phospholipid, and it shows a nonlinear structure, with two fatty acid tails and a phosphate-linked headgroup. Together with other types of lipids, it assembles into the lipid bilayer which serves as the structural scaffold for other components. , In this aspect, the hybrid assembly of nonlinear polymer structures can serve as a bioinspired polymeric self-assembly route. ,, As one of the unique molecular architectures, graft copolymer (GCP) shows the advantages in self-assembled aggregates with multiple morphologies and structures. − Especially, many researches have demonstrated that the vesicles formed by GCPs displayed enhanced resistance to nonspecific protein adsorption and controlled drug release behavior through tuning the hydrophilic–hydrophobic balance. , However, almost no attention has been devoted to the cooperative self-assembly studies of binary GCPs, partly due to their relatively challenging synthesis and characterization. , Thus, the understanding of structure–function relationship of binary GCP self-assembly systems is urgently needed, and also of practical importance in design of versatile carriers for biomedical application.…”

“…Interestingly, as the f hydrophilic of binary GCPs increased up to 60% (GCP mix60 ), hollow vesicles (PM mix60 ) with diameter of 170 nm were observed (Figure F). A perusal of the literature showed all the single components of BCPs and GCPs were found to form vesicles at f hydrophilic < 50%, especially within the range of 25–45%, and the vesicles formation at such a high f hydrophilic was exceptional. ,,− It implied the distinctive packing pattern of binary GCPs during the cooperative self-assembly, which demands the detailed molecular understanding of nanostructure evolution. Here, some structural features of the hybrid vesicle will be discussed afterward when it is used as the drug/protein carrier.…”

“…As proposed in Scheme , in the PMs, the insoluble PCL segments constitute the vesicle wall. PM o‑i30 involves the looping of hydrophobic PCL backbone into the core and the tailing of grafted hydrophilic PEG to form the corona . On the contrary, PM i‑o30 involves the tailing of grafted hydrophobic PCL into the core and the looping of hydrophilic PEG backbone to form corona .…”

“…21−23 Especially, many researches have demonstrated that the vesicles formed by GCPs displayed enhanced resistance to nonspecific protein adsorption and controlled drug release behavior through tuning the hydrophilic−hydrophobic balance. 24,25 However, almost no attention has been devoted to the cooperative self-assembly studies of binary GCPs, partly due to their relatively challenging synthesis and characterization. 23,26 Thus, the understanding of structure− function relationship of binary GCP self-assembly systems is urgently needed, and also of practical importance in design of versatile carriers for biomedical application.…”

A Versatile Method to Prepare Protein Nanoclusters for Drug Delivery

“…Deoxygenated Hb‐NCs (DeoxyHb‐NCs) was obtained by exposing the carbon monoxide Hb‐NCs (CoHb‐NCs) solution to visible light under N 2 atmosphere for 1 h with the addition of a trace amount of Na 2 S 2 O 4 . The oxygenated Hb‐NCs (OxyHb‐NCs) state could be obtained by flowing O 2 gas over DeoxyHb‐NCs solution for 0.5 h. The O 2 binding and release ability of Hb at different oxygen partial pressures was evaluated via oxygen half‐saturation pressure ( P 50 ) and cooperativity (Hill coefficient), which were performed as described by our previous report …”