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がん温熱治療用磁性ナノ粒子の磁化容易軸配向による発熱向上

Shi Guannan 横浜国立大学 DOI:info:doi/10.18880/00013299

2020.06.15

概要

がんの三大治療法である手術療法、抗がん剤などの化学療法、放射線治療においては、身体への侵襲による傷跡や副作用といった患者への負担が多大であることが課題である。近年、低侵襲かつ副作用が軽微ながんの治療法として磁気ハイパーサーミア(磁気を用いた温熱治療)が注目されている。特に磁性ナノ粒子を発熱体として用いた磁気ハイパーサーミアが国内外で活発に研究されている。磁性ナノ粒子は、磁気共鳴画像法 (Magnetic resonance imaging: MRI)における造影剤や、磁気粒子イメージング(Magnetic particle imaging: MPI)におけるトレーサーとして使用することも可能なために、磁性ナノ粒子を用いることによる診断と治療を融合した新しい医療技術、セラノスティクス(Theranostics:治療 Therapeutics と診断 Diagnostics)の実現が期待されている。

診断や治療の様々な使用目的に応じて、粒径などの構造特性や磁気特性、被覆材料の 化学的性質などの観点から、適切な磁性ナノ粒子を設計することが必要となる。そこで 本研究では、生体適合性及び発熱量に優れた磁性ナノ粒子を実現することを目的とした。まず、磁性ナノ粒子を生体に取り込む際に異物反応を起こさないように生体膜の親水部 と同じ構造を持つカチオン性の高分子材料を用いて、表面がアニオン性の Fe3O4 ナノ粒子(M-300) を静電的にコーティングした磁性ポリイオンコンプレックス会合体 (M-300/P100M100)に着眼した。コーティングによる磁性ナノ粒子の分散性及び液中粒径、磁気特性への影響を明らかにした。交流磁化曲線の面積から磁気損失に相当する発熱量 を算出し、未修飾のM-300 と同程度の発熱効率が得られることを確認した。

磁性ナノ粒子を用いた磁気ハイパーサーミアにおいては、人体サイズで励磁可能な磁場強度・周波数下で十分な発熱を得ることが課題となっている。まず磁性ナノ粒子の磁化容易軸を配向させ、交流磁化特性を制御する手法を試みた。固体中に分散する磁性ナノ粒子(Resovist)を作製する際に、直流磁場を印加することにより、磁性ナノ粒子の磁化容易軸を配向させた。この磁化容易軸の配向により磁気異方性を付与し、発熱量を向上させることに成功するとともに、そのメカニズムを解明した。さらに特定の粒径をもつ粒子群を抽出した磁気分画粒子では、粒径分散のある従来粒子よりも発熱量が増加することも明らかとなった。一般的には、粒子自体の回転による磁気応答であるブラウン緩和が存在しない、固体中に分散する磁性ナノ粒子では、溶媒中に分散する磁性ナノ粒子よりも発熱量が低下するが、磁化容易軸を配向固定させた磁性ナノ粒子は、溶媒中と比較して高い発熱を示すという新しい知見を得るに至った。

以上の研究により、磁性ナノ粒子の化学修飾による生体適合性の向上を達成したこと、及び磁性ナノ粒子の磁化容易軸の配向や粒径分布を制御することにより、磁気ハイパー サーミアでの発熱量向上に成功したことは、磁性ナノ粒子の医療応用の発展に貢献する 極めて意義のある研究成果である。

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