Regulating vesicle bilayer permeability and selectivity via stimuli-triggered polymersome-to-PICsome transition

Abstract

Compared to liposomes, polymersomes of block copolymers (BCPs) possess enhanced stability, along with compromised bilayer permeability. Though polyion complex vesicles (PICsomes) from oppositely charged block polyelectrolytes possess semipermeable bilayers, they are unstable towards physiologically relevant ionic strength and temperature; moreover, permselectivity tuning of PICsomes has remained a challenge. Starting from a single component diblock or triblock precursor, we solve this dilemma by stimuli-triggered chemical reactions within pre-organized BCP vesicles, actuating in situ polymersome-to-PICsome transition and achieving molecular size-selective cargo release at tunable rates. UV light and reductive milieu were utilized to trigger carboxyl decaging and generate ion pairs within hydrophobic polymersome bilayers containing tertiary amines. Contrary to conventional PICsomes, in situ generated ones are highly stable towards extreme pH range (pH 2-12), ionic strength (~3 M NaCl), and elevated temperature (70°C) due to multivalent ion-pair interactions at high local concentration and cooperative hydrogen bonding interactions of pre-organized carbamate linkages. 1 1234567890():,; PEO-b-P(NCMA-co-DPA) PEO-b-P(NCMA-co-DEA) PEO-b-P(DCMA-co-DPA) PEO-b-PNCMA-b-PDPA Fig. 2 Chemical structures of four types of amphiphilic block copolymers (BCPs) used in this study.

Avidin Localizations in pH-Responsive Polymersomes for Probing the Docking of Biotinylated (Macro)molecules in the Membrane and Lumen

“…Some of them focus on the creation of vesicle-templated porous nanocapsules with a precise control of pore size and selective permeability. [24][25][26][27] Another attractive and useful alternative is the membrane integration of biomacromolecules (enzymes, protein pores, protein channels, etc.) into the polymersomes.…”

“…There are only a few published experimental studies of measuring passive and active permeability of polymersomes for small molecules. 27,[55][56][57][58] Previous own studies on cyclic switching of (multi)enzymatic reactions have been focused on pH-and/or temperatureresponsive enzyme-loaded nanoreactors based on photocrosslinked polymersomes (Psomes), hollow capsules and their multicompartments. 49,50,59,60 For most of these reactive enzymes were enclosed into the inner cavity of the polymeric vesicles during their formation process (in situ loading).…”

Feedback and Communication in Active Hydrogel Spheres with pH Fronts: Facile Approaches to Grow Soft Hydrogel Structures

“…Important features such as threshold sensing, [19] bistability, [20, 21] oscillations, [22–24] and pattern formation [25] could be shown on a molecular level. Building on this, CRNs were combined into materials to control physiochemical responses, [26, 27] capsule permeability, [28, 29] patterns, [30] communication, [31–34] gating, [35] chemotaxis, [36] diffusiophoresis, [37, 38] and hydrogel formation [39–44] . Hence, feedback‐driven CRNs can offer a great control on a molecular scale, but their behavioral diversification demands for a proper sketch of the kinetics and network topology, and the step from molecular systems to materials continues to be a significant challenge.…”

Emerging era of “somes”: polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy

“…After systemic administration, polymersomes assemble passively at the tumor site via enhanced permeation and retention (EPR) effect and release the drug at the target site [8]. The integration of stimuli-sensitive chemistry can also control the drug release from polymersomes [9]. Because of these benefits, polymersomes have been widely explored in numerous biomedical applications, for example, in drug delivery [10], gene delivery [11], and diagnostics [12].…”