Advances in Ultrasmall Inorganic Nanoparticles for Nanomedicine: From Diagnosis to Therapeutics

Inorganic nanoparticles possess unique physicochemical properties that make them attractive candidates for diverse applications in nanomedicine, including as contrast agents and as therapeutics. However, many inorganic nanoparticles are composed of high-atomic-number elements, raising safety concerns due to potential long-term retention in the body. However, ultrasmall inorganic nanoparticles (UINPs), i.e., those that are less than ∼5 nm in diameter, can offer the advantage of rapid renal clearance from the body, reducing toxicity risks associated with prolonged exposure and thereby creating a path toward clinical translation. In this review, we discuss current knowledge on the design and functionalization of UINPs, exploring their capabilities from diagnosis to therapeutics, with examples including radiosensitization, photothermal, and anti-inflammatory catalytic therapies. In addition, we discuss their limitations, the approaches taken to solve their limitations, and progress of UINPs toward clinical translation. Through this discussion, we aim to provide a comprehensive perspective on how UINPs are advancing the field of nanomedicine, underscoring their potential to significantly improve bioimaging and therapeutic outcomes.