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文獻名：An oligopeptide/aptamer-conjugated dendrimer-based nanocarrier for dual-targeting delivery to bone

 

 

作者： Mingxing Ren,^abc   Yuzhou Li,^abc   He Zhang,^abc   Lingjie Li,^abc   Ping He,^abc   Ping Ji^abc  and  Sheng Yang ^abc  

^a College of Stomatology, Chongqing Medical University, 426 Songshibei Road, Yubei District, Chongqing, China
^b Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China

^c Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China

 

 

摘要：Bone targeting is one of the most potentially valuable therapeutic methods for medically treating bone diseases, such as osteoarthritis, osteoporosis, nonunion bone defects, bone cancer, and myeloma-related bone disease, but its efficacy remains a challenge due to unfavorable bone biodistribution, off-target effects, and the lack of cell specificity. To address these problems, we synthesized a new dual-targeting nanocarrier for delivery to bone by covalently modifying the G4.0 PAMAM dendrimer with the C11 peptide and the CH6 aptamer (CH6-PAMAM-C11). The molecular structure was confirmed using ¹H-NMR and FT-IR spectroscopy. CLSM results showed that the novel nanocarrier could successfully accumulate in the targeted cells, mineralized areas and tissues. DLS and TEM demonstrated that CH6-PAMAM-C11 was approximately 40–50 nm in diameter. In vitro targeting experiments confirmed that the C11 ligand had a high affinity for HAP, while the CH6 aptamer had a high affinity for osteoblasts. The in vivo biodistribution analysis showed that CH6-PAMAM-C11 could rapidly accumulate in bone within 4 h and 12 h and then deliver drugs to sites of osteoblast activity. The components of CH6-PAMAM-C11 were well excreted via the kidneys. The accumulation of many more CH6-PAMAM-C11 dual-targeting nanocarriers than single-targeting nanocarriers was observed in the periosteal layer of the rat skull, along with aggregation at sites of osteoblast activity. All of these results indicate that CH6-PAMAM-C11 may be a promising nanocarrier for the delivery of drugs to bone, particularly for the treatment of osteoporosis, and our research strategy may serve as a reference for research in targeted drug, small molecule drug and nucleic acid delivery.

 

 

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