Overcoming the Dilemma of Permeability and Stability of Polymersomes through Traceless Cross-Linking

Abstract

Metrics & MoreArticle Recommendations CONSPECTUS: In nature, cells are highly compartmentalized into many organelles that are well separated from the rest of the cellular space by unique membrane structures, which are of crucial importance to allow cells to perform various physiological functions in such a small and crowded space. Learning from the ubiquitous membrane structures of cells and organelles has continuously inspired the development of artificial self-assembled nanostructures, with lipid vesicles (liposomes) and polymer vesicles (polymersomes) being the most representative examples. Similar to the membrane-bound structures of cells and organelles, both liposomes and polymersomes contain an aqueous interior enclosed by a bilayer membrane. Therefore, liposomes and polymersomes have been extensively investigated to mimic the fundamental structures and functions of living cells. For example, liposomes and polymersomes have been successfully engineered as nanocarriers, smart nanoreactors, artificial organelles, and so on. Notably, living cells can exchange both energy and materials with surrounding environments, benefiting from the selective permeability of lipid membranes. The permselectivity of cell membranes is thus an essential attribute of living organisms. Compared to liposomes, polymersomes have increased structural stability but low membrane permeability. Indeed, polymersomes are almost impermeable to small molecules, ions, and even water molecules. To improve the permeability of polymersomes, much effort has been devoted to the incorporation of channel proteins, the coassembly of oppositely charged block copolymers (BCPs), the development of stimuli-responsive BCPs, and so on. Despite great achievements, these approaches generally lead to decreased stability of polymersomes and, sometimes, polymersome disintegration. In this Account, we discuss our recent efforts to reconcile the stability and permeability of polymersomes via a traceless cross-linking approach. Although cross-linking reactions within bilayer membranes generally lead to decreased permeability, the traceless cross-linking approach can concurrently improve the stability and permeability of polymersomes. Specifically, stimuliresponsive polymersomes undergo either covalent cross-linking or noncovalent cross-linking reactions under specific stimuli to increase bilayer stability, while the cross-linking processes can concurrently permeabilize polymersome bilayers through crosslinking-driven hydrophobic-to-hydrophilic transitions. Notably, unlike conventional cross-linking processes requiring additional cross-linkers, the traceless cross-linking process does not involve extra cross-linking agents but takes full advantage of the in situ generated active moieties. By taking advantage of the simultaneous modulation of the stability and permeability of polymersomes via traceless cross-linking, these polymersomes can be further engineered as smart nanocarriers and nanoreactors. The robustness and generality of this approach have been validated ...

Surface Engineering of Nanoparticles toward Cancer Theranostics

“…The scintillating ZnS-A NPs on the NP surface could play dual roles of converting X-rays into UV light to induce azobenzene isomerization and cross-linking the nanocapsules to maintain structural integrity. Unlike other polymeric nanocapsules undergoing irreversible disruption after payload release, PETAzo@ZnS-A nanocapsules could maintain stability through surface cross-linkage to further promote tumor retention and achieve remotely controlled pulsatile drug delivery through permeability switchable membranes (Figure B–D) …”

“…Unlike other polymeric nanocapsules undergoing irreversible disruption after payload release, PETAzo@ZnS-A nanocapsules could maintain stability through surface cross-linkage to further promote tumor retention and achieve remotely controlled pulsatile drug delivery through permeability switchable membranes (Figure 6B−D). 50 In addition to achieving controlled drug release, surface modification also can be used to realize off−on switchable function or TME-responsive cross-linking to enhance tumor accumulation. We recently fabricated a core−shell structure ZrMOF@MnO 2 by modifying the surface of porphyrinic ZrMOF with MnO 2 to realize off−on switchable function, in which the photodynamic and fluorescence activities could be turned off by the MnO 2 coating and turned on by intracellular GSH mediated MnO 2 reduction, thus achieving controlled photodynamic therapy.…”

Direct Radiolabeling of Trastuzumab-Targeting Triblock Copolymer Vesicles with 89Zr for Positron Emission Tomography Imaging

“…Polymeric nanocarriers have been shown to be advantageous as theranostic agents that can easily combine imaging (diagnostic) and therapeutic functions. , Unlike single-molecule therapeutics conjugates and rigid organic or inorganic nanoparticles, which can have low blood circulation, tissue toxicity, low drug loading, and adverse immune responses, soft polymeric vesicles (polymersomes) assembled from amphiphilic block copolymers demonstrated high therapeutic payloads and can be obtained as biocompatible and biodegradable with various functionalities providing environmental stimuli-induced responses . In contrast to phospholipid vesicles (liposomes) that may suffer short circulation half-lives, low mechanical stability in vivo , drug leakage, and fusion, the block copolymers provide excellent control over the polymersome structure and physicochemical properties. − For example, varying the polymerization degree of the hydrophilic blocks in poly­( N -vinylcaprolactam) n - b -poly­(dimethylsiloxane) m - b -poly­( N -vinycaprolactam) n (PVCL n -PDMS m -PVCL n ) and poly­( N -vinylpyrrolidone) n - b -PDMS m - b -poly­( N -vinylpyrrolidone) n (PVPON n -PDMS m -PVPON n ) triblock copolymers while keeping the ratio of PDMS/PVCL or PDMS/PVPON was shown to modulate the size of small (<500 nm) vesicles where increasing the length of the hydrophilic block decreased the size of a small vesicle. − A superior in vivo stability of synthetic polymersomes assembled from poly­(3-methyl- N -vinylcaprolactam)- b -poly­( N -vinylpyrrolidone) over liposomes has been shown to decrease doxorubicin-induced cardiotoxicity …”

Biomimetic Protocells Featuring Macrophage‐Like Capture and Digestion of Protein Pathogens

“…[1][2][3][4] More specifically, breakthroughs are being made in the development of artificial organelles (AOs) DOI: 10.1002/smtd.202300257 and protocells for tomorrow's medicine to treat human incurable diseases related to biological dysfunctions. [5][6][7][8] To this end, different polymeric multicompartments such as polymersomes, [9,10] hollow capsules (polyelectrolyte capsules formed by layer-by-layer techniques), [11,12] proteinosomes, [13][14][15] and coacervate microdroplets [16,17] still mimics their biological counterparts. Generally, to perform active biological functions of these therapeutically oriented multicompartments, enzymes for ROS production and detoxification of superoxide and H 2 O 2 , [10,18,19] induction of protein/peptide or polysaccharide degradation, [20][21][22][23] or transformation of other smaller bioactive molecules are successfully integrated.…”