| RRC ID |
61406
|
| 著者 |
Nomoto T, Fukushima S, Kumagai M, Miyazaki K, Inoue A, Mi P, Maeda Y, Toh K, Matsumoto Y, Morimoto Y, Kishimura A, Nishiyama N, Kataoka K.
|
| タイトル |
Calcium phosphate-based organic-inorganic hybrid nanocarriers with pH-responsive on/off switch for photodynamic therapy.
|
| ジャーナル |
Biomater Sci
|
| Abstract |
Photodynamic therapy (PDT) is a promising treatment modality for malignant tumors in a light-selective manner. To improve the PDT efficacy, numerous kinds of nanocarriers have been developed to deliver photosensitizers (PSs) selectively into the tumor through leaky tumor-associated vasculature. However, the corresponding prolonged retention of the nanocarrier in the bloodstream may lead to unfavorable photochemical damage to normal tissues such as skin. Here, we report an organic-inorganic hybrid nanocarrier with a pH-responsive on/off switch of PDT efficacy. This hybrid nanocarrier is constructed by hydrothermal synthesis after simple mixing of calcium/phosphate ions, chlorin e6 (amphiphilic low molecular weight PS), and poly(ethylene glycol)-b-poly(aspartic acid) (PEG-PAsp) copolymers in an aqueous solution. The hybrid nanocarrier possesses a calcium phosphate (CaP) core encapsulating the PSs, which is surrounded by a PEG shielding layer. Under physiological conditions (pH 7.4), the nanocarrier suppressed the photochemical activity of PS by lowering the access of oxygen molecules to the incorporated PS, while PDT efficacy was restored in a pH-responsive manner because of the dissolution of CaP and eventual recovery of access between the oxygen and the PS. Owing to this switch, the nanocarrier reduced the photochemical damage in the bloodstream, while it induced effective PDT efficacy inside the tumor cell in response to the acidic conditions of the endo-/lysosomes.
|
| 巻・号 |
4(5)
|
| ページ |
826-38
|
| 公開日 |
2016-5-26
|
| DOI |
10.1039/c6bm00011h
|
| PMID |
26971562
|
| MeSH |
A549 Cells
Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / therapeutic use
Blood Vessels / drug effects
Calcium Phosphates / chemistry*
Cell Survival
Chlorophyllides
Drug Carriers / chemistry*
Drug Delivery Systems
Erythrocytes / cytology
Female
Humans
Mice
Mice, Inbred BALB C
Nanomedicine
Nanoparticles / chemistry*
Neoplasms, Experimental / drug therapy
Oxidative Stress
Particle Size
Photochemotherapy / methods*
Photosensitizing Agents / chemistry*
Polyethylene Glycols / chemistry
Porphyrins / chemistry*
|
| IF |
6.183
|
| リソース情報 |
| ヒト・動物細胞 |
A549(RCB0098) |
