Construction of Eukaryotic Cell Biomimetics: Hierarchical Polymersomes‐in‐Proteinosome Multicompartment with Enzymatic Reactions Modulated Protein Transportation

Abstract

The eukaryotic cell is a smart compartment containing an outer permeable membrane, a cytoskeleton, and functional organelles, presenting part structures for life. The integration of membrane‐containing artificial organelles (=polymersomes) into a large microcompartment is a key step towards the establishment of exquisite cellular biomimetics with different membrane properties. Herein, an efficient way to construct a hierarchical multicompartment composed of a hydrogel‐filled proteinosome hybrid structure with an outer homogeneous membrane, a smart cytoskeleton‐like scaffold, and polymersomes is designed. Specially, this hybrid structure creates a micro‐environment for pH‐responsive polymersomes to execute a desired substance transport upon response to biological stimuli. Within the dynamic pH‐stable skeleton of the protein hydrogels, polymersomes with loaded PEGylated insulin biomacromolecules demonstrate a pH‐responsive reversible swelling‐deswelling and a desirable, on‐demand cargo release which is induced by the enzymatic oxidation of glucose to gluconic acid. This stimulus responsive behavior is realized by tunable on/off states through protonation of the polymersomes membrane under the enzymatic reaction of glucose oxidase, integrated in the skeleton of protein hydrogels. The integration of polymersomes‐based hybrid structure into the proteinosome compartment and the stimuli‐response on enzyme reactions fulfills the requirements of eukaryotic cell biomimetics in complex architectures and allows mimicking cellular transportation processes.

Gas-shearing synthesis of core–shell multicompartmental microparticles as cell-like system for enzymatic cascade reaction

“…Inspired by the compartmentalized architecture of eukaryotic cells, core-shell multicompartmental microparticles ('synthetic (artificial) cells') have been also created to mimic complex physiological responses in natural cells [9]. For this purpose multicompartmental microparticles based on coacervates [10], capsosomes [11], vesosomes [12], polymersomes [13] and other hybrid vesicles [14] were investigated. Also phase separation and Pickering emulsions are common methods for fabricating multicompartmental vesicles but major restrictions, including poor control over the properties of the microparticles, remain to exist [15,16].…”

Artificial Organelles with Orthogonal‐Responsive Membranes for Protocell Systems: Probing the Intrinsic and Sequential Docking and Diffusion of Cargo into Two Coexisting Avidin–Polymersomes

“…For mimicking abovementioned cellular (multi)compartments (e.g., artificial organelles [ 2–5 ] and protocells), [ 6–8 ] different synthetic vesicles (e.g., liposomes, [ 9–11 ] hollow capsules, [ 12–14 ] polymersomes [ 15–18 ] and proteinosomes [ 5,6,19,20–22 ] ) and their multicompartments [ 23–26 ] have been designed. Increasing the complexity and diversity of compartments is a crucial issue for mimicking iterative and/or feedback‐controlled processes of and between cellular compartments, [ 27–29 ] for mimicking dynamic self‐assembly and disassembly within protocells, [ 7,20 ] and for mimicking fusion of cellular compartments.…”

Multivalent Protein‐Loaded pH‐Stable Polymersomes: First Step toward Protein Targeted Therapeutics

“…[ 42–46 ] For most of these reactive enzymes they were mainly enclosed into the inner cavity of the polymeric vesicles during their formation process (in situ loading), [ 42–44,46 ] that is similar to formation processes of other enzymatic nanoreactors using (non‐)crosslinked Psomes. [ 14,28,47,48 ] Further own works also demonstrated i) the ability of loading and release of therapeutic hormone such as insulin, [ 49 ] ii) the loading of enzymes in Psomes through a post loading process of swollen Psomes, [ 50 ] and iii) the ability to equip the Psomes´ surface with reactive groups (azido or adamantane groups) that allow a more controlled post‐(=surface)‐functionalization. [ 51,52 ] A subsequent post‐functionalization of the Psomes surface was achieved using covalent azide‐alkyne click reaction, functionalized pH‐responsive Psomes with folate targeting antennae were also reported, [ 15 ] promoting drug release in the acidified endosomal compartment.…”