Reversibly Switching Bilayer Permeability and Release Modules of Photochromic Polymersomes Stabilized by Cooperative Noncovalent Interactions

Abstract

We report on the fabrication of photochromic polymersomes exhibiting photoswitchable and reversible bilayer permeability from newly designed poly(ethylene oxide)-b-PSPA (PEO-b-PSPA) diblock copolymers, where SPA is spiropyran (SP)-based monomer containing a unique carbamate linkage. Upon self-assembling into polymersomes, SP moieties within vesicle bilayers undergo reversible phototriggered isomerization between hydrophobic spiropyran (SP, λ2 > 450 nm irradiation) and zwitterionic merocyanine (MC, λ1 < 420 nm irradiation) states. For both SP and MC polymersomes, their microstructures are stabilized by multiple cooperative noncovalent interactions including hydrophobic, hydrogen bonding, π-π stacking, and paired electrostatic (zwitterionic) interactions, with the latter two types being exclusive for MC polymersomes. Control experiments using analogous block copolymers of hydrophobic SP monomer with a carbonate linkage (SPO) and conventional spiropyran methacrylate monomer (SPMA) containing a single ester functionality were then conducted, revealing that carbamate-incurred hydrogen bonding interactions in PEO-b-PSPA are crucial for polymersome stabilization in the zwitterionic MC state. Moreover, reversible phototriggered SP-to-MC polymersome transition is accompanied by membrane polarity and permeability switching from being nonimpermeable to selectively permeable toward noncharged, charged, and zwitterionic small molecule species below critical molar masses. Intriguingly, UV-actuated MC polymersomes possess two types of release modules: (1) sustained release upon short UV irradiation duration by taking advantage of the unexpectedly slow spontaneous MC-to-SP transition kinetics (t1/2 > 20 h) under dark conditions; (2) on-demand and switchable release under alternated UV-vis light irradiation. We further demonstrate photoswitchable spatiotemporal release of 4',6-diamidino-2-phenylindole (DAPI, cell nuclei-staining dye) within living HeLa cells.

Engineering Polymersomes for Diagnostics and Therapy

“…[148] DAPI, a cell nuclei DNA-intercalating dye with blue emission, was encapsulated into the aqueous interior of polymersomes. Upon intracellular release from polymersomes, DAPI spontaneously entered the cell nuclei and reported the extent of release through enhanced fluorescence emission.…”

Isomerization and rearrangement of boriranes: from chemical rarities to functional materials

“…Although polymers incorporating either traditional photochromic systems (e.g., spiropyrans and DTEs; [47,48]) or organoboron functionalities [49][50][51][52][53] have been widely explored, photochromic polymers with a switchable boron core remained unknown until recently [54]. These polymers (Fig.…”

Stimuli-responsive polymersomes and nanoreactors

“…140 In order to realize a reversible permeability-enhancing process, Liu et al proposed a novel strategy for facile, switchable, and reversible regulation of polymersome bilayer permeability. 141 A spiropyran-based monomer, containing a unique carbamate linkage (SPA), was introduced in the amphiphilic block copolymer PEO-b-PSPA to generate photochromic polymersomes. Hydrophilic zwitterionic merocyanine (MC) states were obtained from SP moieties upon light irradiation with λ 1 < 420 nm and MC polymersomes showed switched-on permeability along with stability because of the hydrophobic and hydrogen bonding interactions and zwitterionic and π−π stacking interactions.…”

“…141 It is worth mentioning that, although a large number of stimuli-responsive polymersomes have been designed and constructed, only a few of them have been investigated and used as nanoreactors. When polymersomes are intended to serve as artificial organelles, activity of encapsulated enzymes should be triggered in a controlled and ondemand manner.…”