2-Nitrobenzyl Borate Based Photolabile Linker for Breakable Polymer Vesicles

Abstract

Fluorescent photolabile groups undergoing convenient synthesis and fast cleavage are being explored because of their increasing utility in both synthetic and biological chemistry. Herein, a model photosensitive poly(ethylene glycol)-lipid of NP-B-PEG with a 2-nitrobenzyl 2-pyridinylmethyl borate hydrophobic tail is synthesized. The (1) H-NMR and absorption spectra analysis of NP-B-PEG upon 365 nm irradiation in water supports a rapid photocleavage of nitrobenzyl borate with the concomitant hydrolysis of 2-pyridinylmethyl borate. It is also shown that the borate tail hydrolyzes slowly in water. Fortunately, when the polymer aqueous solution is loaded with the hydrophobic doxorubicin (DOX), the borate hydrolysis can be much retarded. The phototriggered experiment shows a two-stage DOX release: first, the slow leakage as a result of the photocleavage of 2-nitrobenzyl borate before the vesicle disintegration; second, the quick DOX precipitation from the disintegrated vesicles induced by the speeding up hydrolysis of 2-pyridinylmethyl borate.

Fabricating Triple-Sensitive Polymer Nano-Aggregates via an Aqueous Iminoboronate Multicomponent Reaction

“…As expected, the hydrophobic INEC tails could be decomposed by light irradiation, acidification, and oxidation, respectively, resulting in the stimuli‐responsive dissociation of polymer nano‐aggregates (since the obtained fragments of PEG‐INEC upon stimuli would be more soluble in water). As shown in Figure A, when irradiated with 365 nm light, the absorption band of PEG‐INEC aqueous solution at 255 nm ascended gradually with an increasingly clear shoulder absorption band at 305 nm, which was ascribed to the ongoing photolysis of nitrobenzyl boronate, which is consistent with our previous work . In fact, further photoreactions would also soon occur and produce diketone and benzoic acid.…”

“…In fact, further photoreactions would also soon occur and produce diketone and benzoic acid. This would not affect the photo‐cleavage of the iminoboronate tails in the nano‐aggregates due to the primary photo‐chemical process . Figure B shows the tunable enhancement of the normalized intensity at 255 nm ( I 255 ) of PEG‐INEC aqueous solution upon irradiation at different light intensities.…”

“…Amphiphilic polymer nano‐aggregates (APNAs) in aqueous media are of fundamental interest in applications like drug carrier systems . The most appealing feature of APNAs lies in that they can stably encapsulate hydrophobic cargoes for prolonged circulation in vivo and effectively deliver the payload to the target tumor site upon stimuli, such as light, pH, temperature, and redox . Furthermore, APNAs are expected to anchor the heterogeneity of cancer cells since the cell canceration usually causes multiple environmental changes at the tumor site.…”

“…Additionally, boronate esters are pH‐ and redox‐sensitive moieties, allowing polymeric carriers to release encapsulated cargoes upon pH and redox changes, respectively . Furthermore, this group recently found that PEG‐lipid vesicles with 2‐nitrobenzyl borate hydrophobic tails could be photo‐dissociated with UV irradiation through the photo‐cleavage of 2‐nitrobenzyl borate . These unique properties of organboron‐based moieties prompted this group to investigate whether methoxypolyethylene glycol amine (mPEG‐NH 2 ), 2‐formylphenylboronic acid (FPBA), and bis(2‐nitrophenyl) ethanediol (BNPE, a nitrobenzyl alcohol derivate) could be used simultaneously to construct a triple‐sensitive boron‐based polymer via an aqueous iminoboronate multi‐component reaction.…”

Photodegradable hydrogels for external manipulation of cellular microenvironments with real-time monitoring

“…To apply this concept, a major focus has been on light-responsive synthetic hydrogel modulated by a light beam. [43][44][45][46][47][48] Through the activation of light-triggered compound, the stiffness of such polymer networks could be controlled in the micrometer scale designedly. Therefore, light-directed activation of caged compound could be considered as a powerful technique in order to spatiotemporally modify hydrogel properties.…”