Biological stimuli responsive drug carriers based on keratin for triggerable drug delivery

Abstract

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.

Graft modification of cellulose: Methods, properties and applications

“…Specially, cellulose-based smart materials with the grafted stimuli-responsive side polymer chains have potential applications, such as active packaging, biosensors, tissue engineering, antimicrobial surfaces, separation and detection, smart clothing. Moreover, the methods of the graft modification of cellulosic materials can be extended to the graft modification of other natural resourced polymers, such as dextran [295e297] and keratin [248,298,299] for various applications.…”

Responsive hybrid (poly)peptide–polymer conjugates

“…Dual-stimulus DOX release was observed at intracellular GSH concentrations (10 mM), and additional release from the nanoparticles was demonstrated upon treatment with trypsin. 229 Moreover, similar GSH-responsive systems have been used to deliver the gemcitabine prodrug (TPE-GEM-RGD) with aggregation-induced emission (AIE) properties for targeted and image-guided cancer therapy. 230 …”

Stimuli-responsive cross-linked micelles for on-demand drug delivery against cancers

“…However, excessively stabilized micelles may prevent the drug from releasing to target sites, thus reducing the therapeutic efficacy [28, 29]. Stimuli-responsive cross-linked micelles (SCMs) are introduced to improve the drug delivery [30–33]. SCMs exhibit unique stability in blood circulation and can better retain the drug contents.…”