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.
Highlights
Compared to liposomes, polymersomes of block copolymers (BCPs) possess enhanced stability, along with compromised bilayer permeability
Reversible addition-fragmentation chain transfer (RAFT) polymerizations using PEG45-based macroRAFT agent afforded a series of amphiphilic BCPs with varying comonomer sequences and compositions, including PEO45-b-P (NCMA0.55-co-DPA0.45)[29], PEO45-b-P(NCMA0.49-co-DEA0.51)[32], and PEO45-b-P(DCMA0.45-co-DPA0.55)[33] diblock copolymers, and PEO45-b-PNCMA17-b-PDPA21 triblock copolymer (Fig. 2, and Supplementary Figs. 2 and 3)
Polymersomes and PICsomes, with distinct bilayer compositions and polarity, represent two main categories of vesicular nanostructures self-assembled from BCPs
Summary
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; permselectivity tuning of PICsomes has remained a challenge. The loading capability and encapsulation stability of PICsomes towards hydrophilic small molecule drugs and functional agents need to be further improved Both polyion complex (PIC) micelles[45,46,47] and PICsomes[29,30,31] are intrinsically sensitive to high ionic strength, pH, and temperature[40], previous literature reports hint, in a retrospective view, that the stability of PICs or interpolyelectrolyte complexes (IPECs) is highly dependent upon local concentrations and sequence arrangement of charged ionpairs[43,44,48,49,50,51]. By taking advantage of the high local concentration of functional moieties (~1–2 mol/L) within hydrophobic bilayers of self-assembled polymersomes[52], we propose a general strategy to in situ generate ion-pair interactions and trigger transformation from polymersomes to PICsomes (Fig. 1)
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