JP2009078993A - Carbon nanohorn - Google Patents
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Abstract
Description
本発明は、薬物伝送システム（Drug Delivery System：DDS）などに有用な、カーボンナノホーンに関するものである。 The present invention relates to a carbon nanohorn useful for a drug delivery system (DDS) and the like.
ナノカーボンの一種であるカーボンナノホーンは、低・無毒性がin vitroおよびin vivoの毒性試験より明らかになってきており、薬物担体としての利用について検討が進められている。 Carbon nanohorn, which is a kind of nanocarbon, has been revealed to be low and non-toxic by in vitro and in vivo toxicity tests, and its use as a drug carrier is being studied.
たとえば、抗炎症剤のデキサメタゾンはカーボンナノホーンに吸着されることが示され、放出されたデキサメタゾンはin vitroでの有効性が確認されている（非特許文献１）。また、抗癌剤のシスプラチンも同様にカーボンナノホーン内に取り込まれることが示され、放出されたシスプラチンはヒト癌細胞に対する殺傷能力を有することも確認されている（非特許文献２）。
このように、カーボンナノホーンは薬物担体としての応用が期待されているが、カーボンナノホーンのみでは、その物理的性質に起因する腫瘍血管の透過亢進に基づくいわゆるEPR効果（Enhanced Permeation and Retention effect）による受動的ターゲティング（passive targetting）が期待できる一方で、腫瘍組織や癌細胞への直接のターゲティング能を有するものではない。 As described above, carbon nanohorns are expected to be used as drug carriers. However, carbon nanohorns alone are passive due to the so-called EPR effect (Enhanced Permeation and Retention effect) based on the enhanced permeability of tumor blood vessels due to their physical properties. While passive targeting can be expected, it does not have direct targeting ability to tumor tissue or cancer cells.
腫瘍組織や癌細胞への直接のターゲティング能を有するものとして、腫瘍組織や癌細胞に特異的に発現している部位または分子に対して生物学的な親和性を有する標的分子を薬物担体に付加し、これらの特異的な結合能を利用して標的指向化を図る能動的ターゲティング(active targeting)が知られているが、ポリマーやミセルを薬物担体とした場合、化学修飾による標的分子の付加自由度には制限があった。 A target molecule with biological affinity for a site or molecule specifically expressed in tumor tissue or cancer cells is added to the drug carrier as having direct targeting ability to tumor tissue or cancer cells However, active targeting that targets these specific binding capabilities is known, but when a polymer or micelle is used as a drug carrier, the target molecule can be freely added by chemical modification. The degree was limited.
本発明は、以上のとおりの背景から、能動的ターゲティングを可能とし、薬物担体としての機能をさらに高めたカーボンナノホーンを提供することを課題としている。 From the background as described above, an object of the present invention is to provide a carbon nanohorn that enables active targeting and further enhances the function as a drug carrier.
本発明は、上記の課題を解決するために、以下のことを特徴としている。 The present invention is characterized by the following in order to solve the above problems.
第１：DDS標的分子が付加されていることを特徴とするカーボンナノホーン。 1st: Carbon nanohorn characterized by the addition of a DDS target molecule.
第２：開孔処理されており、開孔部にDDS標的分子が付加されていることを特徴とする上記第１のカーボンナノホーン。 Second: The first carbon nanohorn according to the first aspect, wherein the first carbon nanohorn is subjected to an opening treatment, and a DDS target molecule is added to the opening.
第３：開孔部に付加分子が付加されており、当該付加分子にDDS標的分子が結合していることを特徴とする上記第２のカーボンナノホーン。 Third: The second carbon nanohorn, wherein an additional molecule is added to the opening, and a DDS target molecule is bound to the additional molecule.
第４：付加分子がタンパク質であることを特徴とする上記第３のカーボンナノホーン。 Fourth: The third carbon nanohorn, wherein the additional molecule is a protein.
第５：薬物が吸着または内包されていることを特徴とする上記第１から第４のいずれかのカーボンナノホーン。 Fifth: The carbon nanohorn according to any one of the first to fourth aspects, wherein the drug is adsorbed or encapsulated.
本発明によれば、カーボンナノホーンにDDS標的分子を付加することで、能動的ターゲティングが可能となり、標的となる組織や細胞などに選択的かつ効率的に薬物を取り込ませることができ、たとえば薬物として抗癌剤を用いた場合には、治療効果を高め副作用を低減することができる。 According to the present invention, by adding a DDS target molecule to carbon nanohorn, active targeting becomes possible, and a drug can be selectively and efficiently taken up into a target tissue or cell, for example, as a drug. When an anticancer agent is used, the therapeutic effect can be increased and side effects can be reduced.
本発明は上記のとおりの特徴をもつものであるが、以下にその実施の形態について説明する。 The present invention has the features as described above, and an embodiment thereof will be described below.
カーボンナノホーンとしては、たとえば、本発明者らがすでに開発して数多くの報告を行っている各種の方法により合成されたものを用いることができる。カーボンナノホーンは、通常は、集合体の組織構造を有するものであり、たとえば、複数の単層カーボンナノホーン（Single Walled Carbon Nanohorn：SWNH）がその閉鎖端部を外方に向けて集合した構造を有している。 As the carbon nanohorn, for example, those synthesized by various methods already developed by the present inventors and reported in large numbers can be used. Carbon nanohorns usually have an aggregate structure. For example, a single walled carbon nanohorn (SWNH) has a structure in which its closed end faces outward. is doing.
本発明においてカーボンナノホーンに付加されるDDS（Drug Delivery System：薬物輸送システム）標的分子は、腫瘍組織や癌細胞などの、標的となる組織や細胞に特異的に発現している部位または分子に対して、リガンド−受容体相互作用、抗原−抗体反応などにより生物学的な親和性を示す分子のことであり、このようなDDS標的分子をカーボンナノホーンに付加することにより、薬物担体としてのカーボンナノホーンおよびこれに吸着または内包された薬物の標的部位への集積を促進することができる。 In the present invention, a DDS (Drug Delivery System) target molecule added to carbon nanohorn is used for a site or molecule specifically expressed in a target tissue or cell, such as a tumor tissue or a cancer cell. In addition, it is a molecule that exhibits biological affinity through ligand-receptor interaction, antigen-antibody reaction, etc., and by adding such a DDS target molecule to carbon nanohorn, carbon nanohorn as a drug carrier In addition, accumulation of a drug adsorbed or encapsulated in the target site can be promoted.
DDS標的分子としての、受容体に特異的なリガンド分子の具体例としては、葉酸等の有機分子などが挙げられる。多くのヒト癌細胞はビタミン葉酸の受容体を表面膜に過剰発現することが知られており（J. A. Reddy and P.S. Low, Crit. Rev. Ther. Drug Carr. Syst., 15, 587 (1998)）、カーボンナノホーンに葉酸を付加することにより、癌細胞への選択的な輸送が実現される。 Specific examples of a receptor-specific ligand molecule as a DDS target molecule include organic molecules such as folic acid. Many human cancer cells are known to overexpress vitamin folate receptors in the surface membrane (JA Reddy and PS Low, Crit. Rev. Ther. Drug Carr. Syst., 15, 587 (1998)). By adding folic acid to carbon nanohorn, selective transport to cancer cells is realized.
その他、リガンド−受容体相互作用、抗原−抗体反応などにより生物学的な親和性を示す分子の具体例としては、各種のペプチドや抗体、たとえば血管作動性腸管ペプチド（vasoactive intestinal peptide）、N-methylscopolamine、TAG-72 antibody、CEA antibody、CA 19-9 antibodyなどが挙げられる。 Other specific examples of molecules that exhibit biological affinity by ligand-receptor interaction, antigen-antibody reaction, etc. include various peptides and antibodies such as vasoactive intestinal peptide, N- Examples include methylscopolamine, TAG-72 antibody, CEA antibody, and CA 19-9 antibody.
DDS標的分子は、カーボンナノホーンに複数付加されていてもよく、複数種が付加されていてもよい。 A plurality of DDS target molecules may be added to the carbon nanohorn, or a plurality of types may be added.
DDS標的分子は、たとえば、開孔処理されたカーボンナノホーンの開孔部に付加することができる。このような開孔部は、本発明者らがすでに提案している酸化等の手段によってカーボンナノホーンの壁部や頂部に形成することができ、この開孔部には、カルボキシル基や水酸基などの置換基を導入することができる。 The DDS target molecule can be added, for example, to the opening portion of the carbon nanohorn subjected to the opening treatment. Such an opening can be formed on the wall or top of the carbon nanohorn by means such as oxidation already proposed by the present inventors, and this opening has a carboxyl group, a hydroxyl group or the like. Substituents can be introduced.
好ましい一例として、開孔部にタンパク質、糖分子などの付加分子を付加し、当該付加分子にDDS標的分子を付加させることができる。たとえば、置換基が導入された開孔部に牛血清アルブミンを結合させ、この牛血清アルブミンにDDS標的分子を結合させることができる。 As a preferred example, an additional molecule such as a protein or a sugar molecule can be added to the opening, and a DDS target molecule can be added to the additional molecule. For example, bovine serum albumin can be bound to the pore part into which the substituent has been introduced, and the DDS target molecule can be bound to this bovine serum albumin.
また、カーボンナノホーンの置換基が導入された開孔部にアミン-PEO3-ビオチンなどのビオチンを結合させ、次いでストレプトアビジンをビオチンと複合化させ、その後、ペプチドなどのDDS標的分子をビオチン化したものをストレプトアビジンと複合化させることができる。 In addition, biotin such as amine-PEO3-biotin is bound to the opening part into which carbon nanohorn substituents are introduced, then streptavidin is complexed with biotin, and then DDS target molecules such as peptides are biotinylated Can be complexed with streptavidin.
タンパク質などの付加分子を介してカーボンナノホーンにDDS標的分子を付加させることで、カーボンナノホーンにDDS標的分子を容易に導入でき、さらに、カーボンナノホーンの生理溶液中における分散性を高めることもできる。 By adding the DDS target molecule to the carbon nanohorn via an additional molecule such as protein, the DDS target molecule can be easily introduced into the carbon nanohorn, and further, the dispersibility of the carbon nanohorn in the physiological solution can be enhanced.
DDS標的分子は、その種類等に応じて可能であれば、カーボンナノホーンの開孔部分に直接結合させるようにしてもよい。あるいは、その種類等に応じて可能であれば、カーボンナノホーンの開孔部以外の外壁または内壁にDDS標的分子を付加するようにしてもよく、この場合、上記したように付加分子を介してDDS標的分子を付加するようにしてもよく、外壁または内壁にDDS標的分子を直接結合するようにしてもよい。 If possible, the DDS target molecule may be directly bonded to the open portion of the carbon nanohorn depending on the type of the DDS target molecule. Alternatively, if possible, the DDS target molecule may be added to the outer wall or the inner wall other than the pores of the carbon nanohorn, depending on the type thereof. A target molecule may be added, or the DDS target molecule may be directly bound to the outer wall or the inner wall.
カーボンナノホーンは、外壁や開孔部分を上記以外の化合物で化学修飾したものであってもよい。たとえば、エチレングリコール、プロピレングリコール等のアルキレングリコールのオリゴマーやポリマー、ポリアルキレンオキシド、ポリビニルエーテル、ポリビニルエステル、ポリビニルピロリドン、クラウンエーテル、シクロデキストリン、またはこれらの誘導体などをカーボンナノホーンに化学修飾することで、カーボンナノホーンの生理溶液中における分散性を高めることができる。これらの化合物を化学修飾する方法については、すでに多くの報告がある。 The carbon nanohorn may be obtained by chemically modifying the outer wall or the open portion with a compound other than the above. For example, by chemically modifying an alkylene glycol oligomer or polymer such as ethylene glycol or propylene glycol, polyalkylene oxide, polyvinyl ether, polyvinyl ester, polyvinyl pyrrolidone, crown ether, cyclodextrin, or a derivative thereof to carbon nanohorn, Dispersibility of the carbon nanohorn in a physiological solution can be enhanced. There have already been many reports on methods for chemically modifying these compounds.
本発明においてカーボンナノホーンに吸着または内包させる薬物の具体例としては、医薬、動物薬などを挙げることができ、より具体的には、ドデタセキシル、シスプラチン等の抗癌剤、デキソメタゾンまたはそのエステル誘導体等の抗炎症剤、光線力学治療用分子などを挙げることができる。 Specific examples of the drug adsorbed or encapsulated in the carbon nanohorn in the present invention include pharmaceuticals, animal drugs and the like, and more specifically, anti-inflammatory agents such as dodetaxil and cisplatin, and anti-inflammatory such as dexomethasone or an ester derivative thereof. Agents, photodynamic therapeutic molecules, and the like.
これらの薬物は、たとえば、酸化開孔されたカーボンナノホーンと薬物とを液相において混合することによりカーボンナノホーンに吸着または内包させることができる。液相溶媒としては、アルコール、ＤＭＦ、ＤＭＳＯ、アセトニトリルなどの極性溶媒と、水との混合溶媒などを用いることができる。 These drugs can be adsorbed or encapsulated in the carbon nanohorns, for example, by mixing the carbon nanohorns that have undergone oxidation pores and the drug in the liquid phase. As a liquid phase solvent, a mixed solvent of polar solvent such as alcohol, DMF, DMSO, and acetonitrile and water can be used.
そこで以下に実施例を示し、さらに詳しく説明する。もちろん、以下の例示によって発明が限定されることはない。 Therefore, an example will be shown below and will be described in more detail. Of course, the invention is not limited by the following examples.
＜実施例１＞
図１に示す手順により、SWNHの開孔部のカルボキシル基に、BSA（牛血清アルブミン）を付加し、次いで葉酸を付加した。
<Example 1>
According to the procedure shown in FIG. 1, BSA (bovine serum albumin) was added to the carboxyl group in the pore opening of SWNH, and then folic acid was added.
SWNHの酸化は、過酸化水素を用いて、光照射下、100 ℃、2時間の条件で行った。酸化開孔したSWNHoxと、Alexa Fluor 488で蛍光標識したBSAを、リン酸緩衝液中、常温にて攪拌しながら、EDC（1-ethyl-3-(3-dimethylamino-propyl)carbodiimide）の存在下に処理してBSAをSWNHoxの開口部の縁に付加した。次いで、得られたBSA-NHと葉酸を、リン酸緩衝液中、常温にて攪拌しながら、EDCの存在下に処理してBSA-NHに葉酸を付加した。 SWNH was oxidized with hydrogen peroxide under light irradiation at 100 ° C. for 2 hours. In the presence of EDC (1-ethyl-3- (3-dimethylamino-propyl) carbodiimide), SWNHox oxidized with pores and BSA fluorescently labeled with Alexa Fluor 488 are stirred in phosphate buffer at room temperature. And BSA was added to the edge of the SWNHox opening. Next, the obtained BSA-NH and folic acid were treated in the presence of EDC while stirring at room temperature in a phosphate buffer to add folic acid to BSA-NH.
純酸素中で行った熱重量分析（TGA）におけるナノホーン、葉酸、およびBSAの各分子の重量減少から、分子量を用いてモル比を算出した。ここで、ナノホーン１本の分子量は、直径４ nm、長さ40 mmの円筒グラフェン構造を仮定して求めた240,000を用いた。 From the weight loss of each molecule of nanohorn, folic acid, and BSA in thermogravimetric analysis (TGA) performed in pure oxygen, the molar ratio was calculated using the molecular weight. Here, as the molecular weight of one nanohorn, 240,000 obtained assuming a cylindrical graphene structure having a diameter of 4 nm and a length of 40 mm was used.
ナノホーン１本当たりに付加したBSAおよび葉酸のモル比の分析結果を表１に示す。 Table 1 shows the analysis results of the molar ratio of BSA and folic acid added per nanohorn.
口腔の表皮癌から得た、葉酸受容体が過剰発現するヒト癌KB細胞を用い、SWNHの葉酸ラベルによる選択的取り込みについて検討した。1×105/dishのKB細胞を37 ℃、5 % CO2の条件で24 時間培養したディッシュに、実施例１で得たFA-BSA-NHの懸濁液を滴下し、37 ℃、5 % CO2の条件で24時間培養した。
Using human cancer KB cells overexpressing folate receptors, obtained from oral epidermoid carcinoma, selective uptake by SWNH folate label was investigated. The suspension of FA-BSA-NH obtained in Example 1 was added dropwise to a dish in which 1 × 10 5 / dish KB cells were cultured for 24 hours at 37 ° C. and 5% CO 2. The cells were cultured for 24 hours under the condition of% CO 2 .
得られた培養物をPBSでリンスした後、添加物を取り込んだ細胞数を、フローサイトメトリーにより測定した。BSA-NH（葉酸なし）についても測定を行った。測定結果を図２に示す。 After rinsing the obtained culture with PBS, the number of cells incorporating the additive was measured by flow cytometry. BSA-NH (without folic acid) was also measured. The measurement results are shown in FIG.
葉酸を付加したBSAナノホーン（FA-BSA-NH）はKB細胞内に効率的に取り込まれ、葉酸なしのBSA-NHと比較してKB細胞への取り込み量の有意な増加が確認された。 BSA nanohorn added with folic acid (FA-BSA-NH) was efficiently taken up into KB cells, and a significant increase in the amount taken up into KB cells was confirmed compared to BSA-NH without folic acid.
なお、葉酸受容体がより少ない通常のヒト細胞を用いて同様の試験を行ったが、FA-BSA-NHと葉酸なしのBSA-NHとの間で細胞への取り込み量に相違は見られなかった。
＜実施例３＞
抗癌剤のドデタセキシル（Doc）を内包させたSWNHの開孔部にアミン-PEO3-ビオチンを付加し、次いでストレプトアビジンを付加した後、DDS標的分子であるMouse anti-TAG-72を付加した。
A similar test was performed using normal human cells with fewer folate receptors, but there was no difference in the amount of cells taken up between FA-BSA-NH and BSA-NH without folate. It was.
<Example 3>
Amine-PEO3-biotin was added to the opening of SWNH encapsulating the anticancer drug dodetaxel (Doc), then streptavidin was added, and then mouse anti-TAG-72, a DDS target molecule, was added.
過酸化水素で処理して開孔部を形成したSWNHに、modified nano-precipitation methodによりDocを導入した。Docの導入量は約20質量％であった。 Doc was introduced into SWNH that had been treated with hydrogen peroxide to form pores by the modified nano-precipitation method. The amount of Doc introduced was about 20% by mass.
洗浄後、得られたDoc＠NHの開孔部のカルボキシル基に、アミン-PEO3-ビオチンを共有結合させて付加し、次いで、Doc＠NHに付加したビオチンにストレプトアビジンを複合させた。ストレプトアビジンの導入量は約25質量％であった。このDoc＠NH-SAのストレプトアビジンに、水溶液中にて、Mouse anti-TAG-72を付加し、Doc＠NH-SA-TAGを得た。
＜実施例４＞
WST-1アッセイ法により細胞毒性試験を行った。ヒト胃癌由来の細胞（ATCC No. CRL5973）細胞を、Docのみ、NH-SA-TAG（Docなし）、Doc＠NH-SA（Tagなし）、またはDoc＠NH-SA-TAGと共に（〜3 μg/ml）、2日間培養した。
After washing, amine-PEO3-biotin was covalently added to the carboxyl group of the resulting Doc @ NH opening, and then streptavidin was conjugated to biotin added to Doc @ NH. The amount of streptavidin introduced was about 25% by mass. Mouse anti-TAG-72 was added to streptavidin of Doc @ NH-SA in an aqueous solution to obtain Doc @ NH-SA-TAG.
<Example 4>
Cytotoxicity tests were performed by WST-1 assay. Cells derived from human gastric cancer (ATCC No. CRL5973) cells with Doc only, NH-SA-TAG (no Doc), Doc @ NH-SA (no tag), or Doc @ NH-SA-TAG ( ~ 3 μg / ml) and cultured for 2 days.
Doc＠NH-SA-TAGを用いた場合における2日間培養後の試料の共焦点蛍光顕微鏡による観察像を図３に示す。なお、蛍光標識にはAlexa 488を用いた。Doc＠SWNH-SA-TAGが胃癌細胞内に取り込まれていることが確認され、ヨウ化プロピジウム染色により、それらの大部分が死滅していることが分かった。 The observation image by the confocal fluorescence microscope of the sample after 2-day culture in the case of using Doc @ NH-SA-TAG is shown in FIG. Alexa 488 was used for fluorescent labeling. It was confirmed that Doc @ SWNH-SA-TAG was incorporated into gastric cancer cells, and propidium iodide staining revealed that most of them were killed.
WST-1アッセイ法の結果を図４に示す。Doc＠NH-SA-TAGは、TAGの効果により優先的に胃癌細胞に取り込まれ、TAGを付けていないDoc＠NH-SAを用いた場合に比較して、効率的に細胞死を起こさせていることが確認できた。 The results of the WST-1 assay are shown in FIG. Doc @ NH-SA-TAG is preferentially taken up by gastric cancer cells due to the effect of TAG, and causes cell death more efficiently than when Doc @ NH-SA without TAG is used. It was confirmed that
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Cited By (2)
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|---|---|---|---|---|
| CN102579337A (en) * | 2012-03-07 | 2012-07-18 | 山东大学 | Long circulation lipid nano-suspension containing docetaxel and preparation method thereof |
| CN105044367A (en) * | 2015-08-03 | 2015-11-11 | 武汉上成生物科技有限公司 | Colloidal gold immunochromatographic assay test strip for detecting dexamethasone residues in milk |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05506251A (en) * | 1991-02-14 | 1993-09-16 | バクスター、インターナショナル、インコーポレイテッド | Binding of growth hormones to liposomes |
| WO1996028188A2 (en) * | 1995-03-16 | 1996-09-19 | Hisamitsu Pharmaceutical Co., Inc. | Method of transmitting target-oriented substances |
| WO2000023476A1 (en) * | 1998-10-16 | 2000-04-27 | Otsuka Pharmaceutical Co., Ltd. | Neovascular-specific peptides |
| JP2005343885A (en) * | 2004-05-07 | 2005-12-15 | Japan Science & Technology Agency | Drug carbon nanohorn composite and method for producing the same |
| WO2007091663A1 (en) * | 2006-02-06 | 2007-08-16 | Nec Corporation | Carbon nanohorn complex having substance encapsulated therein and method of producing the same |
-
2007
- 2007-09-25 JP JP2007248261A patent/JP5250229B2/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH05506251A (en) * | 1991-02-14 | 1993-09-16 | バクスター、インターナショナル、インコーポレイテッド | Binding of growth hormones to liposomes |
| WO1996028188A2 (en) * | 1995-03-16 | 1996-09-19 | Hisamitsu Pharmaceutical Co., Inc. | Method of transmitting target-oriented substances |
| WO2000023476A1 (en) * | 1998-10-16 | 2000-04-27 | Otsuka Pharmaceutical Co., Ltd. | Neovascular-specific peptides |
| JP2005343885A (en) * | 2004-05-07 | 2005-12-15 | Japan Science & Technology Agency | Drug carbon nanohorn composite and method for producing the same |
| WO2007091663A1 (en) * | 2006-02-06 | 2007-08-16 | Nec Corporation | Carbon nanohorn complex having substance encapsulated therein and method of producing the same |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102579337A (en) * | 2012-03-07 | 2012-07-18 | 山东大学 | Long circulation lipid nano-suspension containing docetaxel and preparation method thereof |
| CN105044367A (en) * | 2015-08-03 | 2015-11-11 | 武汉上成生物科技有限公司 | Colloidal gold immunochromatographic assay test strip for detecting dexamethasone residues in milk |
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| JP5250229B2 (en) | 2013-07-31 |
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