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Development of Theranostics Agents for Site-specific Cancer Treatment Based on Near-infrared Absorbing Complexes

基于近红外吸收复合物的用于特定部位癌症治疗的治疗诊断剂的开发

基本信息

批准号：
21J10204
负责人：
澤村瞭太
金额：
$ 0.96万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2021
资助国家：
日本
起止时间：
2021-04-28 至 2023-03-31
项目状态：
已结题

项目摘要

本研究では，光音響イメージングによる診断と光熱療法による治療を組み合わせたがんのセラノスティクスの実現を目指し，環境応答性の近赤外吸収を示すジラジカル白金(II)錯体を基体した，がんへピンポイントに作用するセラノスティクス試薬の創製を目指す．本年度は大きく分けて2つの検討を実施した．1点目は，昨年度から実施している，がん細胞への標的指向性付与を志向した葉酸修飾錯体について，ヒト乳腺癌細胞株MCF-7への導入試験を行った．錯体の培地への仕込み濃度を2倍の40 μMとしたところ，細胞内から錯体由来の近赤外吸収を明瞭に観測できた．錯体の導入機構については依然として決定的な証拠が得られていない状況ではあるが，葉酸修飾に伴い，細胞内へのPt(II)の導入量は非修飾錯体の場合の約11倍に増加した．本成果は共有結合的戦略に基づく本錯体の高機能化の実現可能性を初めて提示したものであり，1件の論文投稿ならびに複数件の学会発表を行った．2点目は，がん組織への選択的送達を志向し，疎水性錯体を内包した両親媒性ポリマーミセルを調製し物性評価を行った．得られたミセルは，ナノサイズの高分子の腫瘍集積性が亢進するEnhanced Permeability and Retention効果に適した粒径で，近赤外吸収・光熱変換を示した．さらにがん細胞へ導入して近赤外レーザー光を照射することで，錯体の光熱変換により細胞増殖を抑制できることが確かめられた．光熱変換に伴う細胞殺傷能については詳細な定量評価を実施中である．以上の検討を通して，ジラジカル白金(II)錯体をがんへピンポイントに作用させるためのセラノスティクス試薬の設計指針の一例を提示し，本研究が最終的に目指す薬剤の物理像を研究開始時点よりも明確化できた．本研究については引き続き検討を続けていく計画である．

This study aims to provide guidance for the realization of photoacoustic diagnostic and photothermal therapeutic combinations and the creation of novel agents for environmental responsiveness and near-infrared absorption of platinum (II) complexes into substrates and for their role in photoacoustic therapy. This year, the study was carried out in two parts. 1. The study was carried out in two parts. 1. The study was carried out in two parts. 2. The study was carried out in two parts. 1. The study was carried out in two parts. 2. The study was carried out in two parts. 1. The study was carried out in two parts. 2. The study was carried out in two parts. 1. The study was carried out in two parts. 2. The study was carried out in two parts. 2. The study was carried out in two parts. 1. The study was carried out in two parts. 2. The study was carried out in two parts. 3. The study was carried out in three parts. 2. The study was carried out in two parts. 3. The study was carried out in three parts. 2. 1. The study was carried out in two parts. 3. The study was carried out in three parts. 2. 1. The study was carried out in two parts. 3. The study was carried out in three parts. 2. 1. The study was carried out in three parts. 1. The study was carried out in three parts. 1 The intracellular origin and near-extracellular absorption of the host cells were determined by double the concentration of 40 μ M in the host cells. The amount of Pt (II) introduced into the cell increased by about 11-fold in the case of folate modification. The results of this study are based on a combination of strategy and the possibility of high functionality of the fault. One paper submission and a number of academic reports were carried out. 2. The purpose of the selection of the fault was to organize the transmission of the fault. Enhanced Permeability and Retention of Polymers due to the increase in their aggregation properties, resulting in suitable particle size, near-infrared absorption and photothermal conversion. In addition, the introduction of light into the cell is not only beneficial to the growth of the cell, but also beneficial to the growth of the cell. Light and heat exchange with cell killing energy, detailed quantitative evaluation and implementation. In this paper, the author discusses the effects of platinum (II) on the physical image of the object, and gives an example of the design guideline of the object. The author finally points out that the physical image of the object should be studied clearly. This study is aimed at exploring the possible ways to improve the quality of the project.