RRC ID 45300
著者 Sano K, Iwamiya Y, Kurosaki T, Ogawa M, Magata Y, Sasaki H, Ohshima T, Maeda M, Mukai T.
タイトル Radiolabeled γ-polyglutamic acid complex as a nano-platform for sentinel lymph node imaging.
ジャーナル J Control Release
Abstract We established a ternary anionic complex constructed with polyamidoamine dendrimer (4th generation; G4) modified with chelating agents (diethylenetriamine pentaacetic acid (DTPA) derivative), polyethyleneimine (PEI), and γ-polyglutamic acid (PGA) as a safe nano-platform for molecular imaging. We prepared indium-111-labeled DTPA-G4/PEI/γ-PGA, and evaluated the effectiveness as a nuclear imaging probe for sentinel lymph node (LN), the first LN that drains the primary tumor. (111)In-DTPA-G4/PEI with strong cationic charge agglutinated with erythrocytes and showed extremely high cytotoxicity. By contrast, the anionic (111)In-DTPA-G4/PEI/γ-PGA had little agglutination activity with erythrocytes and no cytotoxicity, indicating their high biocompatibility. (111)In-DTPA-G4/PEI/γ-PGA was highly taken up by macrophage cells (high populations in LNs) comparable to (111)In-DTPA-G4/PEI. The uptake mechanisms of (111)In-DTPA-G4/PEI/γ-PGA were suggested to be both phagocytosis and γ-PGA-specific pathway. Upon administration of each (111)In-labeled nano-platform into rat footpads intradermally, significantly higher radioactivity of (111)In-DTPA-G4/PEI/γ-PGA was observed in the first draining popliteal LN when compared with that of (111)In-DTPA-G4/PEI. Moreover, (111)In-DTPA-G4/PEI/γ-PGA clearly visualized the sentinel LN with single photon emission computed tomography (SPECT) compared with (111)In-DTPA-G4/PEI. Thus, (111)In-DTPA-G4/PEI/γ-PGA can be useful as a nano-platform for molecular imaging including sentinel LN imaging.
巻・号 194
ページ 310-5
公開日 2014-11-28
DOI 10.1016/j.jconrel.2014.08.025
PII S0168-3659(14)00612-9
PMID 25238958
MeSH Animals Erythrocytes / drug effects Indium Radioisotopes* / chemistry Indium Radioisotopes* / pharmacokinetics Lymph Nodes / diagnostic imaging* Macrophages / drug effects Macrophages / metabolism Mice Nanoparticles* Pentetic Acid / chemistry Phagocytosis / drug effects Polyglutamic Acid / analogs & derivatives* Polyglutamic Acid / chemistry Polyglutamic Acid / pharmacokinetics Radiopharmaceuticals* / chemistry Radiopharmaceuticals* / pharmacokinetics Rats Tissue Distribution Tomography, Emission-Computed, Single-Photon
IF 7.727
引用数 5
WOS 分野 PHARMACOLOGY & PHARMACY CHEMISTRY, MULTIDISCIPLINARY
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)