Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 12, Issue -, Pages 7469-7482Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S139775
Keywords
osteoporosis; microRNA; bone resorption; targeting delivery; nanoparticle
Funding
- Key Project of Chinese National Programs for Research and Development [2016YFC1102705]
- National Science Technology Support Plan Projects [2014BAI04B07]
- National Natural Science Foundation [81370971, 81722031, 81770873, 81470715, 81771043]
- Shanghai Health System Academic Leader Program [2017BR009]
- Guangdong Natural Science Funds [2014A030313358, 2015A030313333]
- Major Science Project in Guangdong Province [2014KZDXM011]
- Science and Technology Planning Project of Guangdong Province [2013B090500105, 2014A020210015]
- Guangdong Natural Science Funds for Distinguished Young Scholars [S2013050013880]
- Recruitment Program of Global Experts 1000 Plan
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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 Asp(8). 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 Asp(8)-PU delivery system, anti-miR214 was delivered to osteoclasts, and bone microarchitecture and bone mass were improved in ovariectomized osteoporosis mice. Therefore, Asp(8)-PU could be a useful bone-resorption surface-targeting delivery system for treatment of osteoclast-induced bone diseases and aging-related osteoporosis.
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