Advances in Functionalized Nanoparticles for Osteoporosis Treatment

Abstract

Osteoporosis (OP) represents a significant global health burden, characterized by reduced bone density and an increased risk of fractures due to imbalances in bone remodeling processes. Traditional therapeutic strategies, while mitigating symptoms, often lack the precision to address the multifactorial nature of OP effectively. In recent years, functionalized nanoparticles have emerged as a versatile platform, offering enhanced drug delivery, targeted therapy, and the potential for theranostic applications in OP treatment. This review examines the various types and architectures of functionalized nanoparticles, emphasizing their unique capabilities in targeting bone tissue and modulating bone metabolism. By focusing on their roles in inflammation modulation, oxidative stress reduction, and promoting bone regeneration, we discuss the mechanisms by which these nanoparticles offer multifunctional, synergistic effects. Additionally, we address the challenges in achieving controlled drug release, biocompatibility, and effective bone tissue penetration, proposing future directions that integrate emerging nanotechnologies, biomechanics, and regenerative medicine approaches to optimize therapeutic outcomes. This comprehensive review provides a foundation for the future development of functionalized nanoparticle therapies, positioning them as promising tools for advanced, personalized OP treatment.

Keywords: bone tissue targeting; drug delivery; functionalized nanoparticles; osteoporosis.

Figure 1

Schematic illustration of the composition and structural framework of functionalized nanoparticles for OP treatment. (Some parts of the figure by Figdraw, www.figdraw.com).

Figure 2

(A) Synthesis and structural design of the UCNP nanocomplex; (B) Near-infrared (NIR) light-triggered osteogenic differentiation of MSCs coupled with real-time monitoring of cellular differentiation, demonstrated both in vitro and in vivo. Reproduced from Yan R, Guo Y, Wang X, et al. Near-infrared light-controlled and real-time detection of osteogenic differentiation in mesenchymal stem cells by upconversion nanoparticles for osteoporosis therapy. ACS Nano. 2022;16(5):8399–8418.

Figure 3

Upconversion luminescence (UCL) spectra of (A) UCNPs-1 and (B) UCNPs-2. Figure 3A Reproduced from Ma X, Luan Z, Zhao Q, et al. NIR-triggered release of nitric oxide by upconversion-based nanoplatforms to enhance osteogenic differentiation of mesenchymal stem cells for osteoporosis therapy. Biomater Res. 2024;28:0058. Distributed under a Creative Commons Attribution License 4.0 (CC BY 4.0). https://creativecommons.org/licenses/by/4.0/. Figure 3B Reproduced from Ye J, Jiang J, Zhou Z, et al. Near-infrared light and upconversion nanoparticle defined nitric oxide-based osteoporosis targeting therapy. ACS Nano. 2021;15(8):13692–13702.

Figure 4

Bone-targeting effect and biotoxicity evaluation of LMEK. (a) Whole-body NIR-II imaging of OVX mice; (b) NIR-II imaging of the forelimbs of mice; (c) NIR-II imaging of the hindlimbs of mice; (d) Ex vivo NIR-II imaging of bones dissected from the LMEK group. Reprinted from Acta Biomaterialia, Cheng C, Xing Z, Hu Q, et al. A bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy. 2024;173:442–456. With permission from Elsevier.

Figure 5

Preparation and Characterization of Bone-Targeted Liposomes. (A) Schematic illustration of the binding of the bone-targeting peptide (DSS)₆ to bone tissue; (B) Synthetic route of DSPE-PEG₂₀₀₀-(DSS)₆; (C) Structural diagram of quercetin-loaded bone-targeted liposomes; (D) Schematic illustration of the preparation process of bone-targeted liposomes loaded with quercetin; (E) Digital photograph of the uniform suspension of quercetin-loaded bone-targeted liposomes in saline. Reprinted from Acta Biomaterialia, Xing X, Tang Q, Zou J, et al. Bone-targeted delivery of senolytics to eliminate senescent cells increases bone formation in senile osteoporosis. 2023;157:352–366. With permission from Elsevier.