Honeycomb-like pH-responsive γ-cyclodextrin electrospun particles for highly efficient tumor therapy.

We report here the tumor-implantable microparticles with a honeycomb-like porous structure. These microparticles were prepared by electrospinning using γ-cyclodextrin (γ-CD) conjugated with 3-(diethylamino)propylamine (DEAP, as a pH-responsive moiety), named γ-CD-DEAP. The resulting microparticles had pore channels (constructed using γ-CD-DEAP) extending into the deep compartment of the microparticles and allowing efficient paclitaxel (PTX, as a chemotherapeutic model drug) entrapment by a simple hole-filling encapsulation process. Importantly, the hydrophobic DEAP (at pH 7.4) in the γ-CD-DEAP microparticles changed to hydrophilic DEAP (at pH 6.8) because of its acidic pH-induced protonation. This phenomenon resulted in an acidic pH-activated particle destruction by a charge-charge repulsion between the protonated DEAP moieties and allowed a pH-triggered release of the encapsulated PTX from the collapsed microparticles. Consequently, γ-CD-DEAP microparticles implanted at the tumor site caused a significant enhancement of the in vitro/in vivo tumor cell ablation, suggesting their significant potential as a chemotherapeutic implant for tumor therapy.