Recent advances in shell-sheddable nanoparticles for cancer therapy.

Cancer remains one of the most incurable diseases associated with high mortality and morbidity. Although extensive studies have been carried out for cancer therapy, there are still no gold standards available for treatment. Spurred by advances in biomaterial sciences, recent efforts have focused on the development of polymeric nanoparticles for site-specific delivery of anticancer drugs. Such nanoparticles have distinct characteristics, including high thermodynamic stability, good biocompatibility, and prolonged circulation in the bloodstream. Owing to these unique features, systemically administered nanoparticles can passively accumulate at tumor tissue with leaky vasculature and poor lymphatic drainage system, which is called the enhanced permeation and retention (EPR) effect. However, the site-specific accumulation of nanoparticles does not guarantee high antitumor efficacy because the conventional nanoparticles release the drugs in a sustained manner via the passive diffusion mechanism, which may not endow tumor tissue with cytotoxic local concentrations of the drugs. To surmount this limitation, nanoparticles that can rapidly release the drug at the tumor site need to be developed. In recent years, it has been demonstrated that shell-sheddable nanoparticles have an ability to rapidly release the drug by recognizing the specific environments of the tumor tissue. After systemic administration, shell-sheddable nanoparticles reach tumor sites via the EPR effect, followed by exposure to tumor microenvironment-specific stimuli which cause a burst release of the drug. Representative stimuli, used to design shell-sheddable nanparticles, include pH, redox, enzymes, temperature, ultraviolet, and ultrasound. In this review, we discuss the recent advances in tumor-specific, shell-sheddable nanoparticles for drug delivery.