Azobenzene-Based Cross-Linked Small-Molecule Vesicles for Precise Oxidative Damage Treatments Featuring Controlled and Prompt Molecular Release

Abstract

Precise therapy has become prevalent in clinical practice owing to its accurate and efficient targeting treatment of diseases. Such treatments involving polymersomes as carriers have great potential to lesion sites without damage to normal tissues. However, due to the inherent thick hydrophobic layer of polymersomes, an instantaneous release response to external stimuli remains a challenge. To tackle this challenge, here, we report on the synthesis and applications of azobenzene-containing photochromic vesicles as delivery vectors. These vesicles are assembled from small-molecule amphiphiles that have been developed to provide a fast response and promote instantaneous release due to molecular size reduction compared with macromolecular polymersomes. After cross-linking, the stability of vesicles under a physiological environment is notably enhanced. By varying UV and visible light irradiation, the "gate" of vesicles can be opened and closed reversibly for the controlled release of capsuled cargoes. In vitro experiments display that the vesicles can be applied to load cysteamine for eliminating excess reactive oxygen. The synthesized vesicles here show high performance in controlled and instantaneous release in cells both in time and space. By our approach, oxidative damage to cellular biomolecules can be substantially reduced.

Surface-Charge-Switchable and Size-Transformable Thermosensitive Nanocomposites for Chemo-Photothermal Eradication of Bacterial Biofilms in Vitro and in Vivo

“…3T3 fibroblasts were seeded into 96-well plates (6000 cells per well). 55 After culturing for 24 h, the culture medium was replaced with new a solution (200 μL) containing GNRs, GNR@SiO 2 , and GNR@P(NIPAM-AA-MAA) at predetermined concentrations (9.43, 18.85, 37.71, 75.42, 150.84, and 301.68 μg Au/mL). The cells were subsequently cultured for 24 h at 37 °C under 5% CO 2 .…”

Temperature-Dependent Capsule Shell Bonding and Destruction Based on Hindered Poly(urea-urethane) Chemistry

“…Capsules with responsive shells have earned increasing attention in the past decades because of their promising applications in targeted delivery, , controlled release, − energy transport/storage, etc. To impart capsule shells with chemical bond dynamicity, researchers have established various methodologies, including incorporating stimuli-responsive small molecules or anchoring reactive molecules and initiators onto the shell. − For instance, Kitayama and Harada prepared capsules via interfacial photo-crosslinking of 2-diethylaminoethyl methacrylate and 2-cinnamoylethyl methacrylate, where protonation and deprotonation of the tertiary amine group controlled the shrinking and swelling of the capsules and thus cargo release . Additionally, polymer capsules with surface morphology responsive to temperature were successfully constructed by Zeng et al.…”

“…by depositing polydopamine functionalized with 2-bromoisobutyryl bromide onto SiO 2 particles, followed by surface-initiated growth of poly- N -isopropylacrylamide . Yao et al prepared “gated” capsule shells with reversible pore formation controlled by a photo-sensitive azobenzene-containing surfactant, which could eliminate excessive reactive oxygen in cellular biomolecules upon the release of encapsulated cysteamine . Most studies in the area of responsive capsule shells focus on employing reactive small molecules, functional groups, and stimuli-responsive polymers for configuration change.…”

“…10 Yao et al prepared "gated" capsule shells with reversible pore formation controlled by a photo-sensitive azobenzene-containing surfactant, which could eliminate excessive reactive oxygen in cellular biomolecules upon the release of encapsulated cysteamine. 11 Most studies in the area of responsive capsule shells focus on employing reactive small molecules, functional groups, and stimuliresponsive polymers for configuration change. Motivated to expand capsule versatility and to equip capsule shells with multiple transformation pathways (e.g., shell bonding in a solid state, morphology change with easy-to-apply stimuli), we sought to prepare capsules with polymeric shells containing dynamic covalent bonds and demonstrate both inter-capsule crosslinking into monoliths and destruction of capsule shells.…”

Thermo- and Light-Responsive Polymer-Coated Magnetic Nanoparticles as Potential Drug Carriers

“…It is the reason that azobenzene compounds could be utilized to tune the characteristics of host materials. A growing number of studies were using azobenzene derivatives covalently linked to polymers as photoactivated drug delivery systems in NPs formed via self-assembly of polymers ( Shibaev et al, 2003 ; Wang et al, 2015 ; Zhang et al, 2019 ; Shi et al, 2021a ; Yao et al, 2021 ). It was reasonable to expect that as soon as the hydrophobic forces and π - π interactions are removed under UV irradiation, the vesicles with drugs dominated by electrostatic forces would expand rapidly to open the “gate” to achieve drug release ( Yao et al, 2021 ).…”