Proteinosomes via Self-Assembly of Thermoresponsive Miktoarm Polymer Protein Bioconjugates

Abstract

To fabricate nanoscale proteinosomes, thermoresponsive miktoarm polymer protein bioconjugates were prepared through highly efficient molecular recognition between the βcyclodextrin modified BSA (CD-BSA) and the adamantyl group anchored at the junction point of the thermoresponsive block copolymer poly(ethylene glycol)-b-poly(di(ethylene glycol) methyl ether methacrylate) (PEG-b-PDEGMA). PEG-b-PDEGMA was synthesized by the Passerini reaction of benzaldehyde-modified PEG, 2-bromo-2-methylpropionic acid, and 1-isocyanoadamantane, followed by the atom transfer radical polymerization of DEGMA. Two block copolymers with different chain lengths of PDEGMA were prepared, and both self-assembled into polymersomes at a temperature above their lower critical solution temperatures (LCST). The two copolymers can undergo molecular recognition with the CD-BSA and form miktoarm star-like bioconjugates. The bioconjugates self-assembled into ∼160 nm proteinosomes at a temperature above their LCSTs, and the miktoarm star-like structure has a great effect on the formation of the proteinosomes. Most of the secondary structure and esterase activity of BSA in the proteinosomes were maintained. The proteinosomes exhibited low toxicity to the 4T1 cells and could deliver model drug doxorubicin into the 4T1 cells.

Single Functional Group Platform for Multistimuli Responsivities: Tertiary Amine for CO2/pH/ROS-Triggered Cargo Release in Nanocarriers

“…For example, keeping a composition similar to that of a linear AB copolymer, the molecular weights of the individual B arms are lowered in AB n -type arrangements, leading to reduced chain entanglement. Therefore, core–shell formulations from the aqueous self-assemblies of miktoarm stars possess highly beneficial traits, including small dimensions, low critical micelle concentrations (CMC), denser corona, enhanced stability, high encapsulation efficiencies, and so forth. − In addition, due to the ease of introducing different polymeric arms, many studies have focused on personalizing miktoarm copolymers with desired functions for better outcomes in intended applications. − In the current study, we utilized the branched architecture to design a stimuli-responsive miktoarm polymer with a tertiary amine group that became an intricate part of the micelle hydrophobic core, offering tuned responsiveness to various stimuli (CO 2 , pH, ROS, and ROS + CO 2 ) and resulting in controlled release of Cur.…”

Cholesterol-Mediated Anchoring of Phospholipids onto Proteinosomes for Switching Membrane Permeability

“…The design and construction of integrated chemical ensembles for mimicking exquisite attributes of living cells attract considerable interest in different research communities. − Biocompartmentalization with functionalized membranes is a prerequisite step toward the design and construction of artificial cell-like microstructures. , Over the past years, strategies toward membrane-delineated compartmentalization have been widely developed focusing on the use of a diverse range of amphiphilic building blocks that underwent spontaneous or directed assembly in aqueous solutions or oil/water mixtures to produce microcompartments including liposomes, , polymersomes, − colloidosomes, , proteinosomes, − as well as membranized coacervates − which successfully showed various biological processes such as in vitro gene expression, chemical communication, biomacromolecule phase separation, modulated membrane permeability, and enzymatic reactions, as well as a wide variety of dynamic behaviors including proliferation, differentiation, fusion, , predation, and exocytosis . Despite these significant advancements in demonstrating advanced cell-like behaviors and functionalities, the composition of the microcompartmental chassis remains quite limited.…”