JP2013538079A - 癌細胞を摘出するための装置、システム、及び方法 - Google Patents
癌細胞を摘出するための装置、システム、及び方法 Download PDFInfo
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Abstract
Description
米国仮特許出願第61/370,630号に対し、優先権を請求する。尚、上記出願は、本明細書に参照として組み込むものとする。
本願は、癌治療のための埋め込み型医療装置、システム、及び方法に関する。特に、本願は、癌細胞遊走を方向付けることにより、腫瘍(例えば、方向付けがなければ、手術不可能であるか、又は腫瘍の再発を招く腫瘍など)の増殖を切除、再配置、又は管理するためのシステム及び方法に関する。
本発明の一実施形態は、細胞の切除又は死滅を目的として腫瘍細胞遊走を促進するための埋め込み型システムを含む。このシステムは、少なくとも1つの支持体を含み、支持体は、支持体表面に沿って腫瘍細胞遊走を方向付けるためのキュー(cue)を提供するように形成された表面を有し、少なくとも1つの支持体は、複数の配列ナノファイバーを含む。好ましくは、上記システムは、少なくとも1つの支持体によって遊走させた腫瘍細胞と接触させるための少なくとも1つの細胞傷害性物質をさらに含む。
本発明の実施形態は、遊走性腫瘍に、別の望ましい遊走経路、すなわち最終的にそれらの死滅又は切除をもたらす経路を提供する埋め込み型装置及びシステムを提供することによって、前述した要求に取り組むものである。特に、悪性腫瘍、特に侵襲性悪性脳腫瘍を管理するために、転移に特有の細胞運動性及び遊走の特性及び力学を有利に利用する革新的埋め込み型装置及びシステムを提供する。腫瘍抽出及び腫瘍運動を、ある位置(例えば、手術不可能な位置)から二次位置(例えば、手術可能な位置又は細胞傷害性シンク)へと誘導するために、埋め込み可能な構造を有利に用いることができる。
腫瘍細胞遊走のための配列ナノファイバーフィルムの製造及び特性決定
当業者には公知のエレクトロスピニング法を用いて、ポリ(カプロラクトン)(PCL)から緩徐分解性ナノファイバーフィルムを製造した。細胞遊走を促進するために、ナノファイバーフィルムを細胞外マトリックスタンパク質であるラミニンでコーティングした。ラミニンは、腫瘍コア周辺でより高い濃度であることがわかったが、これは、このタンパク質が腫瘍細胞遊走に有意な役割を果たしうることを示している。
スムーズンド阻害剤であるシクロパミンを評価して、腫瘍細胞にアポトーシスを誘導するのに必要な有効薬物濃度を決定した。腫瘍細胞の生存能は、様々な濃度のシクロパミンで測定した。健全な細胞(例えば、ニューロン及び神経膠)は、薬物への暴露により影響されなかった。しかし、結果は、コラーゲンヒドロゲルスカフォールドを30μMのシクロパミンと結合させるべきであることを示した。
24匹のRowett Nude Ratに、U87mgのGFP細胞(ヒトグリア芽細胞腫細胞系である)を接種した。7日後、ラットに腫瘍細胞を接種し、5mmスカフォールドを脳内の腫瘍部位付近に埋め込んだ。腫瘍は、脳表面から深さ2mmの地点に接種した。導管は、脳表面から1.5mmの地点に埋め込んだ。
Claims (34)
- 細胞の切除又は死滅を目的として腫瘍細胞遊走を促進するための埋め込み型システムであって、
支持体表面に沿って腫瘍細胞遊走を方向付けるためのキューを提供するように形成された表面を有する少なくとも1つの支持体であって、複数の配列ナノファイバーを含む少なくとも1つの支持体と、
前記少なくとも1つの支持体を介して遊走させた腫瘍細胞と接触させるための少なくとも1つの細胞傷害性物質と
を含む、埋め込み型システム。 - 前記複数の配列ナノファイバーが、チューブ状構造物を形成する、請求項1に記載のシステム。
- 前記複数の配列ナノファイバーが、チューブ状構造物内に配置されている、請求項1に記載のシステム。
- 前記チューブ状構造物が、ポリカプロラクトン、ポリウレタン、又はこれらの組合せから形成される環状チューブを含む、請求項3に記載のシステム。
- 前記少なくとも1つの細胞傷害性物質が、複数の配列ナノファイバーの少なくとも一部にテザリング又は結合している、請求項1に記載のシステム。
- 前記少なくとも1つの細胞傷害性物質が、ポリマーシンク材料にテザリング又は結合している、請求項1に記載のシステム。
- 前記ポリマーシンク材料が、ヒドロゲルを含む、請求項6に記載のシステム。
- 前記細胞傷害性物質が、シクロパミン、ホノキオール、フレグレレート、ドキソルビシン、又はこれらの組合せを含む、請求項1に記載のシステム。
- 少なくとも1つの支持体の全部又は一部が、一方向腫瘍細胞遊走を促進するための1つ以上の生化学的キューを含む、請求項1に記載のシステム。
- 複数のナノファイバーが、細胞外マトリックスタンパク質、増殖因子、サイトカイン、ペプチド、及びこれらの組合せからなる群から選択されるコーティングを含む、請求項1に記載のシステム。
- 前記コーティングが、複数の配列ナノファイバーの長さに沿って均一に配置されている、請求項10に記載のシステム。
- 前記コーティングが、複数の配列ナノファイバーの第1端から、複数の配列ナノファイバーの第2端まで、複数の配列ナノファイバーの長さに沿って、濃度勾配を呈して配置され、前記第2端は第1端から遠位にある、請求項10に記載のシステム。
- 前記濃度勾配が、腫瘍細胞の一方向遊走を促進するのに有効である、請求項12に記載のシステム。
- 前記濃度勾配が、非腫瘍細胞の二方向遊走を促進するのに有効である、請求項12に記載のシステム。
- 前記ナノファイバーが、合成ポリマーである、請求項1に記載のシステム。
- 前記ナノファイバーフィルムが、ミエリン又は基底膜タンパク質のコーティングを含む、請求項9〜15に記載のシステム。
- 前記ナノファイバーフィルムが、ラミニンコーティングを含む、請求項16に記載のシステム。
- 前記ナノファイバーが、約400nm〜800nmの直径を有する、請求項1に記載のシステム。
- 前記複数のナノファイバーが、約5ミクロン〜20ミクロンの厚さを有するナノファイバーフィルムの形態である、請求項1に記載のシステム。
- 前記複数の配列ナノファイバーが、600nm〜800nmの直径を有する合成ポリマーファイバーであり、これらは、前記ファイバーの長さに沿った濃度勾配を有する細胞外マトリックスタンパク質でコーティングされている、請求項1〜19のいずれか一項に記載のシステム。
- 前記細胞傷害性物質が、アポトーシス誘発因子に共有結合したコラーゲンヒドロゲルを含む、請求項20に記載のシステム。
- 前記ヒドロゲルは、少なくとも一部が、細胞不透過性のパウチに含まれている、請求項21に記載のシステム。
- 細胞の切除又は死滅を目的として腫瘍細胞遊走を促進するための埋め込み型装置であって、
支持体表面に沿って腫瘍細胞遊走を方向付けるためのキューを提供するように形成された表面を有する少なくとも1つのフィルムを含み、前記表面は、表面に沿った細胞の一方向又は二方向増殖をもたらすためのコーティング材料勾配を含む、埋め込み型装置。 - 表面に沿って遊走した腫瘍細胞と接触させるために配置される細胞傷害性物質をさらに含む、請求項23に記載の装置。
- 腫瘍運動をin vivoで誘導するための方法であって、
腫瘍細胞が存在する組織部位に、腫瘍細胞の遊走を第1組織位置から、選択した第2位置に向けるための物理的誘導キューを提供する1つ以上の表面構造を有する装置を埋め込むステップを含む、方法。 - 前記表面構造が、ナノファイバー又は溝を含む、請求項30に記載の方法。
- 組織埋め込み部位に別の誘導手段を適用するステップをさらに含み、前記誘導手段が、電界、1つ以上の生化学的キュー、又は細胞接種を含み、前記表面構造の物理的誘導キューと協働して、選択した第2位置に腫瘍細胞の遊走を向ける、請求項30又は31に記載の方法。
- 前記表面構造が、400nm〜800nmの直径を有する複数の配列ナノファイバーを含み、前記ナノファイバーが、細胞外マトリックスタンパク質でコーティングされている、請求項30又は31に記載の方法。
- 前記腫瘍細胞が、髄芽腫細胞又は悪性グリオーマ細胞を含む、請求項30又は31のいずれか一項に記載の方法。
- 患者を治療するための方法であって
支持体表面に沿って腫瘍細胞遊走を方向付けるためのキューを提供するように形成された表面を有する支持体を含む装置を患者の腫瘍部位に埋め込むステップであって、前記支持体が、複数の配列ナノファイバーを含むステップと、
続いて、前記支持体表面に沿って遊走させた腫瘍細胞を死滅させるか、又は切除するステップと
を含む、方法。 - 前記組織部位が、腫瘍又は切除した腫瘍の空隙を含む、請求項35に記載の方法。
- 前記支持体の少なくとも一部に沿って遊走した腫瘍細胞を細胞傷害性物質と接触させることをさらに含む、請求項35に記載の方法。
- 前記細胞傷害性物質が、埋め込まれる装置の一部である、請求項37に記載の方法。
- 前記埋め込み型装置によって、腫瘍細胞を、第1領域から、原発性腫瘍から離れた第2領域に再配置させた後、腫瘍細胞を死滅させる、又は切除する、請求項35〜38のいずれか一項に記載の方法。
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