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

Abstract

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.

The Coming of Age of Neodymium: Redefining Its Role in Rare Earth Doped Nanoparticles

“…In vivo results confirmed effective accumulation of the nanostructures in bone tissue of a mouse. Moreover, in ovariectomized mice treated with RENPs and NIR irradiation, the bone loss was significantly reduced compared to nontreated control, indicating reversal effect on osteoporosis . A few more recent examples include Y. Zhang et al .…”

Nitric Oxide Induces Immunogenic Cell Death and Potentiates Cancer Immunotherapy

“…Gaseous molecules such as hydrogen (H 2 ), nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide (H 2 S), and sulfur dioxide (SO 2 ) are demonstrated to influence a wide range of physiological process and have been developed for diverse biomedical applications including cancer therapy. − As a prominent and pleiotropic gasotransmitter, NO can influence abundant physiological processes in living organisms. − For instance, NO at a high dose (>500 nM) is tumoricidal and can be used alone or in conjunction with other treatment modalities, thus revealing its potential application in tumor therapy. − Moreover, recent studies have shown that NO can modulate the immunosuppressive tumor microenvironment by activating macrophages to an antitumorigenic state, increasing T cell infiltration and reducing PD-L1 expression. − NO regulates the behavior and activity of infiltrating T cells through facilitating vasculature normalization and promoting intrinsic extracellular matrix degradation. − This suggests the presence of immunomodulatory activity of NO. However, to the best of our knowledge, whether the NO-induced direct effect on tumor cells consists of cytotoxicity with immunogenic characteristics has not been studied to date.…”

Upconversion nanoparticles regulated drug & gas dual-effective nanoplatform for the targeting cooperated therapy of thrombus and anticoagulation

“…As a highly reactive chemical, NO has a short diffusion radius (40–200 μm) [ 53 ]. Therefore, delivery of NO to platelets in a light-triggered and targeted manner would be more effective and desirable [ 54 ]. For investigating the in vivo release capacity of NO, we designed intracellular NIR-triggered NO release experiments.…”