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A bone-resorption surface-targeting nanoparticle to deliver anti-miR214 for osteoporosis therapy
Mingxiang Cai1, Li Yang2, Shufan Zhang1
1Engineering Research Center of Tooth Restoration and Regeneration, Department of Oral Implantology, School of Stomatology, Tongji University, Shanghai.
Abstract:
With increasing fracture risks due to fragility, osteoporosis is a global health problem threatening postmenopausal women. In these patients, osteoclasts play leading roles in bone loss and fracture. How to inhibit osteoclast activity is the key issue for osteoporosis treatment. In recent years, miRNA-based gene therapy through gene regulation has been considered a potential therapeutic method. However, in light of the side effects, the use of therapeutic miRNAs in osteoporosis treatment is still limited by the lack of tissue/cell-specific delivery systems. Here, we developed polyurethane (PU) nanomicelles modified by the acidic peptide Asp8. Our data showed that without overt toxicity or eliciting an immune response, this delivery system encapsulated and selectively deliver miRNAs to OSCAR+ osteoclasts at bone-resorption surface in vivo. With the Asp8-PU delivery system, anti-miR214 was delivered to osteoclasts, and bone microarchitecture and bone mass were improved in ovariectomized osteoporosis mice. Therefore, Asp8-PU could be a useful bone-resorption surface-targeting delivery system for treatment of osteoclast-induced bone diseases and aging-related osteoporosis.
Insights
New polyurethane nanomicelles target osteoclasts, improving bone density in osteoporosis models. This delivery system shows promise for treating bone loss diseases without significant toxicity or immune response.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Osteoporosis Research
Background:
- Osteoporosis poses a global health challenge, particularly for postmenopausal women, with osteoclasts driving bone loss and fracture risk.
- Current osteoporosis treatments face limitations due to the need for targeted delivery of therapeutic agents like microRNAs (miRNAs).
- Developing tissue-specific delivery systems is crucial for effective miRNA-based gene therapy in osteoporosis.
Purpose of the Study:
- To develop a novel, targeted delivery system for miRNAs to osteoclasts.
- To evaluate the efficacy and safety of this system in treating osteoporosis in a mouse model.
Main Methods:
- Development of polyurethane (PU) nanomicelles modified with an acidic peptide (Asp 8 ).
- In vivo assessment of nanomicelle targeting specificity to OSCAR + osteoclasts at bone-resorption sites.
- Evaluation of therapeutic effects of delivered anti-miR214 on bone microarchitecture and bone mass in ovariectomized osteoporosis mice.
Main Results:
- The Asp 8 -PU nanomicelles demonstrated selective delivery of miRNAs to osteoclasts in vivo without apparent toxicity or immune response.
- Delivery of anti-miR214 using the Asp 8 -PU system significantly improved bone microarchitecture and bone mass in osteoporosis mouse models.
- The system effectively targeted osteoclasts on the bone-resorption surface.
Conclusions:
- Asp 8 -PU nanomicelles represent a promising bone-resorption surface-targeting delivery system.
- This system holds potential for the therapeutic treatment of osteoclast-induced bone diseases, including aging-related osteoporosis.
- Targeted delivery of miRNAs via Asp 8 -PU offers a viable strategy for managing osteoporosis.
