Overcoming the stability, toxicity, and biodegradation challenges of tumor stimuli-responsive inorganic nanoparticles for delivery of cancer therapeutics.

: Stimuli-responsive nanomaterials for cancer therapy have attracted much interest recently due to their potential for improving the current standard of care. Different types of inorganic nanoparticles are widely employed for the development of these strategies, but in some cases safety concerns hinder their clinical translation. This review aims to provide an overview of the challenges that inorganic nanoparticles face regarding their stability, toxicity, and biodegradability, as well as the strategies that have been proposed to overcome them. : The available information about the and biocompatibility, as well as the biodegradability of the following nanoparticles, is presented and discussed: superparamagnetic iron oxide nanoparticles, gold nanoparticles, graphene and mesoporous nanoparticles made of silicon or silicon oxide. The toxicology of inorganic nanoparticles is greatly affected by many physicochemical parameters, and their surface modification emerges as the main intervention to improve their biocompatibility and tailor their performance for specific biomedical applications. : Even though many different studies have been performed regarding the biological behavior of inorganic nanoparticles, long-term data is still scarce, limiting our capacity to evaluate the proposed nanomaterials for clinical use. The role of biodegradability in different therapeutic contexts is also discussed.