On-demand relief of local pain would allow patients to control the timing, intensity and duration of nerve blocks in a safe and non-invasive manner. Ultrasound would be a suitable trigger for such a system, as it is in common clinical use and can penetrate deeply into the body. Here, we demonstrate that ultrasound-triggered delivery of an anaesthetic from liposomes allows the timing, intensity and duration of nerve blocks to be controlled by ultrasound parameters. On insonation, the encapsulated sonosensitizer protoporphyrin IX produced reactive oxygen species that reacted with the liposomal membrane, leading to the release of the potent local anaesthetic tetrodotoxin. Repeatable ultrasound-triggered nerve blocks were achieved in vivo, with the nerve-block duration depending on the extent and intensity of insonation. There was no detectable systemic toxicity and tissue reaction was benign in all groups. On-demand, personalized local anaesthesia could be beneficial for the management of relatively localized pain states and could potentially minimize opioid use.

Introduction: 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. Areas covered: The available information about the in vitro and in vivo 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. Expert opinion: Even though many different studies have been performed regarding the biological behavior of inorganic nanoparticles, long-term in vivo 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.