Preparation and characterization of DOX loaded keratin nanoparticles for pH/GSH dual responsive release.
Smart drug carriers are the current need of the hour in controlled drug delivery applications. In this work, pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated through two-step strategies. Keratin nanoparticles were first prepared by desolvation method and chemical crosslinking, followed by electrostatic adsorbing doxorubicin (DOX) to afford drug loaded keratin nanoparticles (KDNPs). The size, size distribution, and morphology of the KDNPs were characterized with dynamic light scattering (DLS) and Scan electronic microscope (SEM). Drug delivery profiles showed that KDNPs exhibited pH and glutathione (GSH) dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay indicated that KDNPs had good blood compatibility. Cellular uptake assay demonstrated that KDNPs could be internalized by A 549 cells through endocytosis. Intriguingly, KDNPs were capable of promoting nitric oxide (NO) release from endogenous donor of S-nitrosoglutathione in the presence of GSH. All of these results demonstrated that keratin based drug carriers had potential for drug/NO delivery and cancer therapy in clinical medicine.
Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Yanmei
Y
Li
Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Xuelian
X
Zhi
Guangdong Medical University, Dongguan 523808, China.
Jiantao
J
Lin
Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China.
Xin
X
You
Jiangsu Key Laboratory of Biofunctional Materials, College of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China. Electronic address: jyuan@njnu.edu.cn.
Jiang
J
Yuan
D000072283:A549 Cells; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D065546:Drug Liberation; D000067493:Dynamic Light Scattering; D004705:Endocytosis / Q000187:drug effects; D005978:Glutathione / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007633:Keratins / Q000737:chemistry*; D007700:Kinetics; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism; D010316:Particle Size; D011817:Rabbits; D055672:Static Electricity
D009569:Nitric Oxide; D007633:Keratins; D004317:Doxorubicin; D005978:Glutathione
Doxorubicin; Keratin; Nitric oxide; Stimuli-sensitive drug delivery