A novel drug carrier with dual triggerable release properties based on keratin graft poly(ethylene glycol) (keratin-g-PEG) copolymers is reported. Keratin-g-PEG copolymers with different graft densities are synthesized through thiol-ene click chemistry. Taking advantage of the amphiphilicity and the thiol groups of the graft copolymer, nanoparticles stabilized with PEG chains and keratin as the core, bearing glutathione (GSH) cleavable cross-links, are fabricated in aqueous solutions. The kerating-PEG copolymer nanoparticles can serve as excellent carriers for doxorubicin hydrochloride salt (DOX$HCl) with a highest loading capacity of 18.1% (w/w). The release of the loaded DOX is sensitive to the concentration of GSH, especially at a GSH concentration of cellular level. Trypsin can further trigger the release of the loaded DOX in the nanoparticles. In vitro cellular uptake experiments indicate that DOX released from the DOX-loaded keratin-g-PEG nanoparticles can be internalized into the cells efficiently, and the loaded DOX shows a faster release into the nuclei of the cells under higher GSH concentrations. The carriers have promising applications as drug carriers for intracellular drug delivery for cancer therapy.
Herein we report a coassembly method toward the preparation of pH-sensitive polymeric vesicular aggregates, using comb-shaped amphiphilic polymers, i.e., cholate grafted poly(L-lysine) (PLL-CA), with an amphiphilic poly(ethylene glycol)-doxorubicin conjugate (PEG-DOX). Because the drug conjugate includes a low-pH labile bond, i.e., benzoic imine, the permeability of the coassembled polymeric vesicles can be tuned by changing either the PLL-CA/PEG-DOX weight ratio or the environmental pH from 7.4 to 6.5. Furthermore, at lower pH values such as 5.0, the vesicles destabilize. The pH sensitivity leads to enhanced uptake of the vesicles by cancer cells (MCF-7) under a condition close to the extracellular environment of solid tumor (pH = 6.5) and subsequent efficient endosome escape after the endocytosis.
Porous liquids are porous materials that have exhibited unique properties in various fields. Herein, we developed a method to synthesize the type I porous liquids via liquefaction of cyclodextrins by chemical modification. The cyclodextrin porous liquids were characterized by Fourier-transform infrared (FTIR) spectroscopy, NMR, matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), circular dichroism (CD), and UV−vis spectroscopy. The measured ionic conductivity of the γ-cyclodextrin porous liquid was 500 times as great as that of its reactants, which was found to be the first instance with such great conductivity for a type I porous liquid. What is more, the γ-cyclodextrin porous liquid had been demonstrated experimentally to have outstanding chiral recognition ability toward pyrimidine nucleosides in water, which was further confirmed by computational simulations. Additionally, enantiomeric excess of the extracted nucleoside was achieved up to 84.81% by convenient extraction from the mixture of racemic nucleosides and γcyclodextrin porous liquid. The great features of the novel cyclodextrin porous liquids could bring opportunities in many fields, including the preparation of chiral separation materials, development of new drug screening mechanisms, and construction of chiral response materials.
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