Metal-polyDNA nanoparticles reconstruct osteoporotic microenvironment for enhanced osteoporosis treatment

Abstract

Current clinical approaches to osteoporosis primarily target osteoclast biology, overlooking the synergistic role of bone cells, immune cells, cytokines, and inorganic components in creating an abnormal osteoporotic microenvironment. Here, metal-polyDNA nanoparticles (Ca-polyCpG MDNs) composed of Ca 2+ and ultralong single-stranded CpG sequences were developed to reconstruct the osteoporotic microenvironment and suppress osteoporosis. Ca-polyCpG MDNs can neutralize osteoclast-secreted hydrogen ions, provide calcium repletion, promote remineralization, and repair bone defects. Besides, the immune-adjuvant polyCpG in MDNs could induce the secretion of osteoclastogenesis inhibitor interleukin-12 and reduce the expression of osteoclast function effector protein to inhibit osteoclast differentiation, further reducing osteoclast-mediated bone resorption. PPi 4− generated during the rolling circle amplification reaction acts as bisphosphonate analog and enhances bone targeting of Ca-polyCpG MDNs. In ovariectomized mouse and rabbit models, Ca-polyCpG MDNs prevented bone resorption and promoted bone repair by restoring the osteoporotic microenvironment, providing valuable insights into osteoporosis therapy.

Cell membrane coated nanoparticles: cutting-edge drug delivery systems for osteoporosis therapy

“…Recent advances in nanomedicine have led to the development of innovative therapeutic approaches aimed at reprogramming the bone immune microenvironment to mitigate osteoporosis. 94,95 The bone microenvironment is a dynamic niche with a complex immune component. Immune cells, including macrophages and T cells, play pivotal roles in regulating bone homeostasis.…”

Metal–Drug Coordination Nanoparticles and Hydrogels for Enhanced Delivery

“…Liu et al. [ 81 ] used rolling circle amplification (RCA) to synthesize very long single‐stranded DNA with CpG motifs. Pyrophosphate (PPi) was a by‐product, which when mixed with Ca 2+ can assemble the RCA product to form NPs (Figure 4E).…”

Polyvalent Aptamer-Functionalized NIR-II Quantum Dots for Targeted Theranostics in High PD-L1-Expressing Tumors

“…They offer high binding specificity, strong affinity, ease of synthesis, chemical stability, and low immunogenicity. − The use of aptamer-based surface modifications can effectively improve the biocompatibility of inorganic materials and improve tumor penetration and retention. − However, challenges arise from the small structure of aptamers, leading to potential problems such as weak binding forces and susceptibility to nucleases in vivo. − To this end, we and others developed the simple and efficient rolling circle amplification (RCA) technique to prepare ultralong single chain polyvalent aptamers (pApt) for the increase of binding force and stability, which can effectively overcome the limitations of short DNA strands, such as poor stability, short blood circulation time, and ease of rapid clearance by the body. − Importantly, the programmable nature of these long single-stranded aptamers allows for flexible synthesis by deleting, adding, or swapping sequences. − However, to the best of our knowledge, the utilization of these long single-stranded aptamers as templates for synthesizing water-soluble quantum dots with NIR-II fluorescence and targeting functionalities has not been reported.…”