Near-Infrared Light and Upconversion Nanoparticle Defined Nitric Oxide-Based Osteoporosis Targeting Therapy

Osteoporosis is one of the most common diseases affecting bone metabolism. Nitric oxide (NO), an endogenous gas molecule involved in osteogenesis, can effectively promote the proliferation and differentiation of osteoblasts. Although exogenous NO can reverse osteoporosis to a certain extent, the transitory half-life and short diffusion radius of NO severely limit its application. In this work, a gas generation nanoplatform of NO with bone targeting property (UCPA) is developed based on the upconversion nanoparticles (UCNPs) that can convert 808 nm near-infrared (NIR) light into UV/blue light, and further stimulate the NO donor (BNN) to release NO. With an adjustment of the output power of the 808 nm NIR, the amount of released NO can be precisely controlled. Both in vitro and in vivo experiments demonstrate the favorable affinity of UCPA to bone due to the modification of alendronate; thus, it can directly release NO in bone and reverse osteoporosis. In addition, the cellular uptake of nanocomposites and intracellular NO release can be observed in preosteoblasts, thereby promoting their differentiation efficiently.