One-Pot Synthesis of Diphenylalanine-Based Hybrid Nanospheres for Controllable pH- and GSH-Responsive Delivery of Drugs

Nano drug delivery systems have attracted much research and clinical interest but they remain challenging with respect to developing controllable, nontoxic, biocompatible and biodegradable nanocarriers. Herein, we report the first pH- and glutathione (GSH)-responsive diphenylalanine (FF)-based hybrid spheres using natural alginate dialdehyde (ADA) as the cross-linker to induce self-assembly of FF and an in situ reducer of Au3+ ions into Au nanoparticles (Au NPs). Not only is the synthesis simple and high-yielding, but also these biocompatible hybrid spheres can encapsulate more than 95% of hydrophobic drug (camptothecin, CPT). Moreover, the CPT-loaded carriers are stable under normal physiological environments, and have excellent pH- and GSH-responsive release at pH 5.0 with 10 mM GSH, which is similar to the tumor microenvironment. Also, these nanocarriers can be taken up by cancer cells and have greater cytotoxicity than free drugs. These attributes make nanospheres very promising for drug loading and delivery, and the method may be used for synthesis of other natural nanospheres as delivery systems.