Dual drug-loaded calabash-like nanomotor as an active therapeutic for enhanced chemo-photothermal therapy of orthotopic glioblastoma

•Double emulsion technique is used as a novel strategy to fabricate nanomotors.•Polymeric nanomotors with tunable sizes are capable of carrying two drugs with distinct solubilities.•The loaded photothermal agent ICG enables both motor actuation and photothermal therapy. Generally, the key to the treatment of glioblastoma is how to effectively cross the blood–brain barrier (BBB) and concentrate the drugs in the lesion. To date, the drug delivery of traditional nanosystems depends on passive diffusion, which lacks the forces to overcome bio-barriers and drive nanoparticles deeply into the diseased sites for effective accumulation. Herein, an active delivery strategy using a calabash-like nanomotor is presented. The nanomotor is prepared by the double emulsion technique, a feasible and simple way to simultaneously load two drugs (photothermal agent ICG and chemotherapeutic drug DOX) with biocompatible polymeric scaffolds. Notably, the near-infrared (NIR) power allows both propulsion and photothermal antitumor effects. With moving ability, this nanomotor achieves superior bio-performances including cellular uptake, BBB crossing, tumor penetration and accumulation. Furthermore, the nanomotor shows improved chemo-photothermal antitumor efficacy towards an orthotopic glioblastoma model, providing a new direction for the treatment of intracranial diseases.