A novel ultrasound-mediated nanodroplet-based gene delivery system for osteoporosis treatment

Shar, Angela; Aboutalebianaraki, Nadia; Misiti, Kaylee; Sip, Yuen Yee Li; Zhai, Lei; Razavi, Mehdi

doi:10.1016/j.nano.2022.102530

Cited by 10 publications

(16 citation statements)

References 45 publications

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“…The bovine serum albumin (BSA)-stabilized IL-4 MDs was fabricated according to previous studies. 18 , 19 ,100 ng/mL IL-4 (R&D system, China) was used based on a previous study. 20 Briefly, 100 ng/mL IL-4, 300 μL perfluorocarbon, and 4 mL of PBS, and 40 mg of bovine serum albumin (BSA, Sigma Aldrich, China) were used for MDs fabrication.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, modification of the bubbles with specific cargos, including targeted delivery of genes, siRNA and cytokines, have also demonstrated remarkable therapeutic effects. 18 Therefore, micro- or nanobubbles-based therapy represents a promising therapeutic approach for drugs/gene delivery system to enhance delivery efficiency and improve tissue repair.…”

Section: Introductionmentioning

confidence: 99%

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Fabrication of Interleukin-4 Encapsulated Bioactive Microdroplets for Regulating Inflammation and Promoting Osteogenesis

Zhang¹,

Cao²,

Jian³

et al. 2023

IJN

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Background Despite the inherent regenerative ability of bone, large bone defect regeneration remains a major clinical challenge for orthopedic surgery. Therapeutic strategies medicated by M2 phenotypic macrophages or M2 macrophage inducer have been widely used to promote tissue remodeling. In this study, ultrasound-responsive bioactive microdroplets (MDs) encapsulated with bioactive molecule interleukin-4 (IL4, hereafter designated MDs-IL4) were fabricated to regulate macrophage polarization and potentiate the osteogenic differentiation of human mesenchymal stem cells (hBMSCs). Materials and Methods The MTT assay, live and dead staining, and phalloidin/DAPI dual staining were used to evaluate biocompatibility in vitro. H&E staining was used to evaluate biocompatibility in vivo. Inflammatory macrophages were further induced via lipopolysaccharide (LPS) stimulation to mimic the pro-inflammatory condition. The immunoregulatory role of the MDs-IL4 was tested via macrophage phenotypic marker gene expression, pro-inflammatory cytokine level, cell morphological analysis, and immunofluorescence staining, etc. The immune-osteogenic response of hBMSCs via macrophages and hBMSCs interactions was further investigated in vitro. Results The bioactive MDs-IL4 scaffold showed good cytocompatibility in RAW 264.7 macrophages and hBMSCs. The results confirmed that the bioactive MDs-IL4 scaffold could reduce inflammatory phenotypic macrophages, as evidenced by changing in morphological features, reduction in pro-inflammatory marker gene expression, increase of M2 phenotypic marker genes, and inhibition of pro-inflammatory cytokine secretion. Additionally, our results indicate that the bioactive MDs-IL4 could significantly enhance the osteogenic differentiation of hBMSCs via its potential immunomodulatory properties. Conclusion Our results demonstrate that the bioactive MDs-IL4 scaffold could be used as novel carrier system for other pro-osteogenic molecules, thus having potential applications in bone tissue regeneration.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fabrication of Interleukin-4 Encapsulated Bioactive Microdroplets for Regulating Inflammation and Promoting Osteogenesis

Zhang¹,

Cao²,

Jian³

et al. 2023

IJN

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“…The creation of Bovine Serum Albumin (BSA)-stabilized bioactive MDs-NFATc1 followed established procedures from previous studies. 35,36 In summary, a mixture of 50 nM NFATc1 siRNA (sc-29,412, Santa Cruz Biotechnology), 300 μL perfluorocarbon, 4 mL of PBS, and 40 mg of BSA (Sigma Aldrich, China) underwent sonication for the fabrication of MDs-NFATc1. Ultracentrifugation was then conducted using the Beckman Coulter Optima XPN-100 ultracentrifuge, spinning for 30 minutes at 14,000 rpm.…”

Section: Fabrication Of Mds-nfatc1/pla-exo Hybrid Scaffoldmentioning

confidence: 99%

Microdroplets Encapsulated with NFATc1-siRNA and Exosomes-Derived from MSCs Onto 3D Porous PLA Scaffold for Regulating Osteoclastogenesis and Promoting Osteogenesis

Luo,

Zhang,

Huang

et al. 2024

IJN

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Osteoporotic-related fractures remains a significant public health concern, thus imposing substantial burdens on our society. Excessive activation of osteoclastic activity is one of the main contributing factors for osteoporosis-related fractures. While polylactic acid (PLA) is frequently employed as a biodegradable scaffold in tissue engineering, it lacks sufficient biological activity. Microdroplets (MDs) have been explored as an ultrasound-responsive drug delivery method, and mesenchymal stem cell (MSC)-derived exosomes have shown therapeutic effects in diverse preclinical investigations. Thus, this study aimed to develop a novel bioactive hybrid PLA scaffold by integrating MDs-NFATc1-silencing siRNA to target osteoclast formation and MSCs-exosomes (MSC-Exo) to influence osteogenic differentiation (MDs-NFATc1/PLA-Exo). Methods: Human bone marrow-derived mesenchymal stromal cells (hBMSCs) were used for exosome isolation. Transmission electron microscopy (TEM) and confocal laser scanning microscopy were used for exosome and MDs morphological characterization, respectively. The MDs-NFATc1/PLA-Exo scaffold was fabricated through poly(dopamine) and fibrin gel coating. Biocompatibility was assessed using RAW 264.7 macrophages and hBMSCs. Osteoclast formations were examined via TRAP staining. Osteogenic differentiation of hBMSCs and cytokine expression modulation were also investigated. Results: MSC-Exo exhibited a cup-shaped structure and effective internalization into cells, while MDs displayed a spherical morphology with a well-defined core-shell structure. Following ultrasound stimulation, the internalization study demonstrated efficient delivery of bioactive MDs into recipient cells. Biocompatibility studies indicated no cytotoxicity of MDs-NFATc1/PLA-Exo scaffolds in RAW 264.7 macrophages and hBMSCs. Both MDs-NFATc1/PLA and MDs-NFATc1/PLA-Exo treatments significantly reduced osteoclast differentiation and formation. In addition, our results further indicated MDs-NFATc1/PLA-Exo scaffold significantly enhanced osteogenic differentiation of hBMSCs and modulated cytokine expression. Discussion: These findings suggest that the bioactive MDs-NFATc1/PLA-Exo scaffold holds promise as an innovative structure for bone tissue regeneration. By specifically targeting osteoclast formation and promoting osteogenic differentiation, this hybrid scaffold may address key challenges in osteoporosis-related fractures.

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“…These unique materials can absorb and retain large amounts of water, making them ideal candidates for delivering osteoporosis drugs directly to the site of bone loss. One of the key advantages of hydrogels is their capacity to be loaded with osteoporosis drugs and implanted precisely at the affected area of bone loss [34] . This targeted delivery approach ensures that the drugs are delivered directly to the site where they are needed most, minimizing systemic exposure and reducing the risk of side effects.…”

Section: Hydrogel-based Drug Deliverymentioning

confidence: 99%

Advancements in nanotechnology for targeted drug delivery in postmenopausal osteoporosis

Mishra,

Shukla

2024

Int. J. Adv. Acad. Stud.

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Recent advancements in drug delivery systems, particularly those utilizing nanotechnology, offer promising avenues for more effective treatment of osteoporosis, a silent and progressive disease prevalent among postmenopausal women. Nanoparticle-based drug delivery systems, including liposomes, polymeric nanoparticles, and micelles, enable targeted delivery of osteoporosis drugs to specific sites in the body, such as areas of bone loss. This targeted approach enhances drug concentration at the desired site while minimizing systemic exposure, thereby reducing adverse effects. Additionally, nanoparticles can be engineered for controlled drug release, prolonging its therapeutic effects. Surface modification of nanoparticles with targeting ligands, like bisphosphonates, further enhances their bone-targeting capabilities, ensuring efficient uptake by bone cells. Hydrogel-based drug delivery systems represent another innovative approach for osteoporosis treatment. Hydrogels, loaded with osteoporosis drugs, provide sustained release of the drug and can promote bone regeneration, enhancing therapeutic potential. Gene therapy, involving the delivery of genes encoding bone-stimulating factors, offers a promising avenue for the long-term management of osteoporosis by targeting underlying molecular mechanisms. Microneedle patches and 3D-printed implants provide minimally invasive and customizable drug delivery methods, enhancing patient convenience and compliance. Despite these advancements, challenges remain, including ensuring the safety and biocompatibility of nanomaterials, optimizing the targeting efficiency of nanoparticles, evaluating long-term effects and risks associated with gene therapy, and addressing the scalability and costeffectiveness of advanced drug delivery systems. However, integrating nanotechnology into drug delivery systems has significantly advanced osteoporosis treatment, offering targeted and personalized therapies with minimized adverse effects and maximized therapeutic efficacy.

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A novel ultrasound-mediated nanodroplet-based gene delivery system for osteoporosis treatment

Cited by 10 publications

References 45 publications

Fabrication of Interleukin-4 Encapsulated Bioactive Microdroplets for Regulating Inflammation and Promoting Osteogenesis

Fabrication of Interleukin-4 Encapsulated Bioactive Microdroplets for Regulating Inflammation and Promoting Osteogenesis

Microdroplets Encapsulated with NFATc1-siRNA and Exosomes-Derived from MSCs Onto 3D Porous PLA Scaffold for Regulating Osteoclastogenesis and Promoting Osteogenesis

Advancements in nanotechnology for targeted drug delivery in postmenopausal osteoporosis

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