| RRC ID |
71968
|
| 著者 |
Yamashita S, Katsumi H, Sakane T, Yamamoto A.
|
| タイトル |
Phosphorylated Serine-Modified Polyamidoamine Dendrimer as an Osteoid Surface-Targeting Drug Carrier.
|
| ジャーナル |
Mol Pharm
|
| Abstract |
The aim of this study was to develop a polyethylene glycol (PEG)-conjugated third-generation polyamidoamine dendrimer (PAMAM) with phosphorylated serine as an osteoid surface-targeting drug carrier for the treatment of bone diseases. We conjugated PAMAM backbones to l-serine and obtained Ser-PAMAM. Then, phosphoric acid and PEG were covalently bound to the Ser-PAMAM to generate PEGylated phosphorylated Ser-PAMAM (PEG-phosSer-PAMAM). Using osteoblast-like cells (MC3T3-E1 cells) cultured in 3D collagen gels, we showed that phosSer-PAMAM adsorbed both the hydroxyapatite and type I collagen components of the bone matrix. Fourier transform infrared spectroscopy analysis indicated that the phosphoryl side chains of phosSer-PAMAM formed electrostatic interactions and hydrogen bonds with the anionic amino acid residues of type I collagen. Mice were intravenously injected with the foregoing molecules, and a tissue distribution study disclosed that the lower limb bone took up about twice as much 111In-labeled PEG-phosSer-PAMAM as 111In-labeled nonphosphorylated PEG-Ser-PAMAM or unmodified PAMAM. An intrabone distribution experiment showed that fluorescein isothiocyanate (FITC)-labeled PEG-phosSer-PAMAM accumulated on the osteoid surfaces, which is associated with bone pathogenesis such as skeletal dysplasias and osteoporosis to a far greater extent than nonphosphorylated PEG-Ser-PAMAM. Our findings indicated that PEG-phosSer-PAMAM is a promising carrier for efficient drug targeting to osteoid surfaces.
|
| 巻・号 |
19(7)
|
| ページ |
2573-2582
|
| 公開日 |
2022-7-4
|
| DOI |
10.1021/acs.molpharmaceut.2c00271
|
| PMID |
35666687
|
| MeSH |
Animals
Bone Matrix
Collagen Type I
Dendrimers* / chemistry
Drug Carriers* / chemistry
Mice
Polyamines
Polyethylene Glycols / chemistry
Serine
|
| IF |
4.321
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
