Polymersomes for Therapeutic Delivery of Protein and Nucleic Acid Macromolecules: From Design to Therapeutic Applications

Abstract

Macromolecule-based therapeutic agents, particularly proteins, antigens, monoclonal antibodies, transcription factors, nucleic acids, and gene editing enzymes, have the potential to offer cures for previously untreatable diseases. However, they present an enormous delivery challenge due to poor absorption and rapid metabolism in the body. Polymersomes have tremendous potential in delivering these agents to their desired intracellular location due to increased circulation times, decreased macromolecule degradation, and decreased immune responses. In this Review, we highlight the key factors in design, development, and improved performance of these vesicles for macromolecular delivery. The recent progress made toward preclinical application of these vesicles for protein and gene delivery is also covered.

Multicompartment Polymeric Nanocarriers for Biomedical Applications

“…[45][46][47] Moreover, polymersomes have the ability to encapsulate both hydrophobic and hydrophilic cargoes within their membrane and aqueous core, respectively, which makes them useful for biomedical applications including drug delivery and constructing therapeutic nanoreactors to mimic biological cascade reactions. [44,48] Different techniques have been extensively used in the preparation of multicompartment polymersomes for biological applications, for example, multi-step self-assembly, [49] double emulsion via microfluidics, [50,51] and emulsion-centrifugation methods. [52,53] Multicompartment polymersomes have generated significant interest for constructing synthetic cellular mimics for multi-enzymatic cascade reactions.…”

“…[ 45–47 ] Moreover, polymersomes have the ability to encapsulate both hydrophobic and hydrophilic cargoes within their membrane and aqueous core, respectively, which makes them useful for biomedical applications including drug delivery and constructing therapeutic nanoreactors to mimic biological cascade reactions. [ 44,48 ]…”

An AIE-driven fluorescent polysaccharide polymersome as an enzyme-responsive FRET nanoprobe to study the real-time delivery aspects in live cells

“…11,12 These unique features of the polymersome nano-assemblies make them distinct nano-scaffolds for loading wide ranges of cargoes irrespective of their solubility parameters. [13][14][15][16][17][18][19] Aggregation induced emission (AIE) is a newly emerging photophysical phenomenon and it is an excel-lent system to exhibit strong fluorescence characteristics in aqueous medium. [20][21][22] AIE-activated polymersomes were reported to study self-assembly aspects or CO 2 capture in polypeptoids, 23 polyacrylate and POSS block copolymers, 24,25 poly (trimethylenecarbonate)s, 26 etc.…”

Thermosensitive Vesicles from Chemically Encoded Lipid‐Grafted Elastin‐like Polypeptides

“…[7,8] Later developed polymersomes,b uilt from amphiphilic synthetic polymers/polypeptides,p rovided more mechanically stable vesicle structures owing to macromolecules of higher molar mass and thicker membranes (5-50 nm). [8][9][10][11] Recent advances in cell-mimicking systems have drawn the attention to genetically encoded protein/peptide-based membrane forming bioamphiphiles for potential design of artificial living systems with self-replication, growth and division properties. [6,[12][13][14] Among proteins of interest, elastin-like polypeptides (ELPs) have been proposed as arelevant class of intrinsically disordered proteins (IDPs).…”