Quantum dot therapeutics: a new class of radical therapies

Traditional therapeutics and vaccines represent the bedrock of modern medicine, where isolated biochemical molecules or designed proteins have led to success in treating and preventing diseases. However, several adaptive pathogens, such as multidrug-resistant (MDR) superbugs, and rapidly evolving diseases, such as cancer, can evade such molecules very effectively. This poses an important problem since the rapid emergence of multidrug-resistance among microbes is one of the most pressing public health crises of our time-one that could claim more than 10 million lives and 100 trillion dollars annually by 2050. Several non-traditional antibiotics are now being developed that can survive in the face of adaptive drug resistance. One such versatile strategy is redox perturbation using quantum dot (QD) therapeutics. While redox molecules are nominally used by cells for intracellular signaling and other functions, specific generation of such species exogenously, using an electromagnetic stimulus (light, sound, magnetic field), can specifically kill the cells most vulnerable to such species. For example, recently QD therapeutics have shown tremendous promise by specifically generating superoxide intracellularly (using light as a trigger) to selectively eliminate a wide range of MDR pathogens. While the efficacy of such QD therapeutics was shown using in vitro studies, several apparent contradictions exist regarding QD safety and potential for clinical applications. In this review, we outline the design rules for creating specific QD therapies for redox perturbation; summarize the parameters for choosing appropriate materials, size, and capping ligands to ensure their facile clearance; and highlight a potential path forward towards developing this new class of radical QD therapeutics.