Development of pH-responsive poly(γ-cyclodextrin) derivative nanoparticles

In this study, we report a novel pH-responsive nanoparticle composed of poly(γ-cyclodextrin) [poly(γCD)] conjugated with functional 3-diethylaminopropyl (DEAP) groups [poly(γCD–DEAP)]. The design of the nanoparticle takes advantage of the biocompatible functional poly(γCD) as the backbone polymer and the unique pH-responsive feature of DEAP as either a hydrophobic moiety (non-ionic DEAP) at pH 7.4 or a hydrophilic moiety (ionic DEAP) at acidic pH. Poly(γCD) was coupled with DEAP and utilized for fabricating pH-responsive nanoparticles for antitumor drug (doxorubicin: DOX) delivery. The experimental results reveal that the poly(γCD–DEAP) nanoparticles increased the release of the encapsulated DOX content when the pH of the solution was decreased to 6.0. This event caused significant increases in the efficiency of cellular DOX uptake and in vitro tumor inhibition. Furthermore, these nanoparticles allow the encapsulation of multiple antitumor drugs into the nanoparticles [utilizing the hydrophobic interactions (between non-ionic DEAP moieties and drugs) and inclusive interactions (between poly(γCD)s and drugs)], thereby suggesting their potential for use in drug combination therapy.