Abstract
Stimuli-responsive nanoparticles hold great promise for drug delivery to improve the safety and efficacy of cancer therapy. One of the most investigated stimuli-responsive strategies is to induce drug release by heating with laser, ultrasound, or electromagnetic field. More recently, cryosurgery (also called cryotherapy and cryoablation), destruction of diseased tissues by first cooling/freezing and then warming back, has been used to treat various diseases including cancer in the clinic. Here we developed a cold-responsive nanoparticle for controlled drug release as a result of the irreversible disassembly of the nanoparticle when cooled to below ∼10 °C. Furthermore, this nanoparticle can be used to generate localized heating under near infrared (NIR) laser irradiation, which can facilitate the warming process after cooling/freezing during cryosurgery. Indeed, the combination of this cold-responsive nanoparticle with ice cooling and NIR laser irradiation can greatly augment cancer destruction both in vitro and in vivo with no evident systemic toxicity.