JP7637940B2 - Method for producing a platinum nanoparticle-containing composition - Google Patents
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- JP7637940B2 JP7637940B2 JP2021017498A JP2021017498A JP7637940B2 JP 7637940 B2 JP7637940 B2 JP 7637940B2 JP 2021017498 A JP2021017498 A JP 2021017498A JP 2021017498 A JP2021017498 A JP 2021017498A JP 7637940 B2 JP7637940 B2 JP 7637940B2
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims description 215
- 229910052697 platinum Inorganic materials 0.000 title claims description 119
- 239000002105 nanoparticle Substances 0.000 title claims description 98
- 239000000203 mixture Substances 0.000 title claims description 68
- 238000004519 manufacturing process Methods 0.000 title claims description 19
- 239000000412 dendrimer Substances 0.000 claims description 33
- 229920000736 dendritic polymer Polymers 0.000 claims description 33
- 229920000962 poly(amidoamine) Polymers 0.000 claims description 33
- -1 platinum ions Chemical class 0.000 claims description 32
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 31
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 21
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 claims description 18
- 238000012986 modification Methods 0.000 claims description 12
- 230000004048 modification Effects 0.000 claims description 12
- 230000009467 reduction Effects 0.000 claims description 12
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims description 9
- 229940000635 beta-alanine Drugs 0.000 claims description 9
- 229930091371 Fructose Natural products 0.000 claims description 8
- 239000005715 Fructose Substances 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 238000001816 cooling Methods 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 description 25
- 201000011510 cancer Diseases 0.000 description 25
- 210000004027 cell Anatomy 0.000 description 14
- 238000006722 reduction reaction Methods 0.000 description 11
- 239000002082 metal nanoparticle Substances 0.000 description 9
- 206010027476 Metastases Diseases 0.000 description 8
- 239000007850 fluorescent dye Substances 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000009401 metastasis Effects 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 210000000130 stem cell Anatomy 0.000 description 8
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- 238000011282 treatment Methods 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 231100000135 cytotoxicity Toxicity 0.000 description 4
- 230000003013 cytotoxicity Effects 0.000 description 4
- 230000004069 differentiation Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000002595 magnetic resonance imaging Methods 0.000 description 4
- 230000008929 regeneration Effects 0.000 description 4
- 238000011069 regeneration method Methods 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
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- 239000000523 sample Substances 0.000 description 3
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- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 231100001261 hazardous Toxicity 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
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- 231100000053 low toxicity Toxicity 0.000 description 2
- 230000005415 magnetization Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 239000007769 metal material Substances 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000009456 molecular mechanism Effects 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 238000010248 power generation Methods 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000001172 regenerating effect Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- RFSUNEUAIZKAJO-VRPWFDPXSA-N D-Fructose Natural products OC[C@H]1OC(O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-VRPWFDPXSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004687 hexahydrates Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000006862 quantum yield reaction Methods 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- FDNAPBUWERUEDA-UHFFFAOYSA-N silicon tetrachloride Chemical compound Cl[Si](Cl)(Cl)Cl FDNAPBUWERUEDA-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000009168 stem cell therapy Methods 0.000 description 1
- 238000009580 stem-cell therapy Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02E—REDUCTION OF GREENHOUSE GAS [GHG] EMISSIONS, RELATED TO ENERGY GENERATION, TRANSMISSION OR DISTRIBUTION
- Y02E60/00—Enabling technologies; Technologies with a potential or indirect contribution to GHG emissions mitigation
- Y02E60/30—Hydrogen technology
- Y02E60/50—Fuel cells
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- Powder Metallurgy (AREA)
- Manufacture Of Metal Powder And Suspensions Thereof (AREA)
Description
本発明は、蛍光及び磁気プローブとして使用できる白金ナノ粒子含有組成物の製造方法に関するものである。 The present invention relates to a method for producing a platinum nanoparticle-containing composition that can be used as a fluorescent and magnetic probe.
ナノマテリアル、光エレクトロニクス、医療等の様々な分野において、ナノ粒子（金属ナノ粒子等）を用いた蛍光プローブの開発が進められている（例えば、特許文献１，２参照）。
特に、医療分野においては特定の標的分子、例えば癌細胞と反応又は結合することによって、高感度に癌細胞を検出することが可能であるので、研究や治療に蛍光プローブは欠かせない。
Fluorescent probes using nanoparticles (metal nanoparticles, etc.) have been developed in various fields such as nanomaterials, optoelectronics, and medicine (see, for example, Patent Documents 1 and 2).
In particular, in the medical field, fluorescent probes are indispensable for research and treatment because they are capable of detecting cancer cells with high sensitivity by reacting with or binding to specific target molecules, such as cancer cells.
特許文献１に記載の発明は、Ｓｉ塩化物等をジメチルホルムアミド含有溶媒中で加熱還流して製造するものである。
この製造方法によると、危険性の高い試薬を用いる必要がないだけではなく後処理の必要もなく、さらには粒子径の揃ったナノ粒子蛍光体を大量生産可能である。
The invention described in Patent Document 1 involves heating and refluxing a silicon chloride or the like in a solvent containing dimethylformamide to produce the compound.
This manufacturing method does not require the use of highly hazardous reagents or post-treatment, and furthermore allows for the mass production of nanoparticle fluorescent materials with uniform particle sizes.
また、特許文献２に記載の発明は、金属化合物を、タンパク質を含むとともにｐＨ調整された水溶液中で還元して、蛍光体組成物を製造するものである。
この製造方法によると、金属ナノ粒子を含む蛍光体組成物を、製造過程で危険性の高い試薬を用いることなく、大量生産可能である。
また、制御された異なる粒子径を持つ種々の金属ナノ粒子を含む蛍光体組成物を幅広く製造可能である。
Moreover, the invention described in Patent Document 2 produces a phosphor composition by reducing a metal compound in an aqueous solution containing a protein and having an adjusted pH.
According to this manufacturing method, it is possible to mass-produce phosphor compositions containing metal nanoparticles without using highly hazardous reagents in the manufacturing process.
It is also possible to produce a wide range of phosphor compositions containing various metal nanoparticles with different controlled particle sizes.
ここで、医療分野で用いられる蛍光プローブに関しては、当然のことながら生体への毒性が無いことが必須であるが、特許文献１に記載の発明は、生体が生存できない有機溶媒中での合成手法であるので、医療分野の蛍光プローブとしては適していない。
また、生体内には可視光を吸収する多様な分子が存在しているため、４００～５７０ｎｍ程度の波長の光は皮膚表面や生体内の分子によって吸収されてしまい、生体の深部からこの波長の蛍光シグナルを観察できないので、癌の診断や幹細胞治療などの高精細な医療診断技術を確立するためには、生体組織に吸収・散乱されることなく生体の深部からでも観察可能な近赤外領域（６００～８５０ｎｍ）に発光波長を有する蛍光プローブでなければならないが、特許文献１に記載の発明は近赤外領域に蛍光特性を持つ蛍光体ではない。
Here, for fluorescent probes to be used in the medical field, it is of course essential that they are not toxic to living organisms. However, the invention described in Patent Document 1 is a synthesis method that is carried out in an organic solvent in which living organisms cannot survive, and is therefore not suitable as a fluorescent probe for the medical field.
Furthermore, because there are various molecules present in the living body that absorb visible light, light with a wavelength of approximately 400 to 570 nm is absorbed by molecules on the skin surface and within the living body, making it impossible to observe fluorescent signals of this wavelength from deep within the living body. Therefore, in order to establish high-definition medical diagnostic techniques for cancer diagnosis, stem cell therapy, and the like, a fluorescent probe must have an emission wavelength in the near-infrared region (600 to 850 nm) that can be observed even from deep within the living body without being absorbed or scattered by biological tissue; however, the invention described in Patent Document 1 is not a phosphor that has fluorescent properties in the near-infrared region.
また、特許文献２に記載されるような蛍光タンパク質は、数分から１時間程度観察に使用すると退色、つまり蛍光物質としての特性を失ってしまう。仮に、これらの蛍光物質を最も退色しない条件(４℃の暗所)で保管しても１，２ヶ月程度で光学特性(明るさ(輝度))が半分以下になる。
すなわち、この蛍光プローブを長期間の経過観察が必要な癌の転移の検査や診断に利用することは困難である。
Furthermore, fluorescent proteins such as those described in Patent Document 2 fade, that is, lose their properties as fluorescent substances, when used for observation for several minutes to an hour. Even if these fluorescent substances are stored under conditions that minimize fading (in a dark place at 4°C), their optical properties (brightness (luminance)) will drop to less than half in about one or two months.
In other words, it is difficult to use this fluorescent probe for the examination and diagnosis of cancer metastasis, which requires long-term follow-up.
そこで、本発明者は、氷冷温度下において白金イオンと第五乃至第七世代のポリアミドアミンデンドリマーとを反応させ白金イオンとポリアミドアミンデンドリマーとの間で化学結合を形成させることで、ポリアミドアミンデンドリマー内に白金イオンを取り込ませる結合工程と、白金イオンを取り込んだポリアミドアミンデンドリマーをフルクトースで還元することで、ポリアミドアミンデンドリマー１０内において白金ナノ粒子を合成する還元工程と、を備える製造方法によって、近赤外領域に蛍光特性を有しつつ生体に対する毒性が低く、しかも長期間退色しない金属ナノ粒子含有組成物を提供した（特許文献３）。 The inventors have provided a metal nanoparticle-containing composition that has fluorescent properties in the near infrared region, has low toxicity to living organisms, and does not fade for a long period of time, by using a manufacturing method that includes a bonding step in which platinum ions are reacted with a fifth- to seventh-generation polyamidoamine dendrimer at ice-cooling temperature to form a chemical bond between the platinum ions and the polyamidoamine dendrimer, thereby incorporating platinum ions into the polyamidoamine dendrimer, and a reduction step in which platinum nanoparticles are synthesized within the polyamidoamine dendrimer 10 by reducing the polyamidoamine dendrimer that has incorporated platinum ions with fructose (Patent Document 3).
このように光を利用した生体イメージング法では、ターゲット分子の時間的・量的な動態・局在を捉えるだけでなく、分子の発現・機能のみならず細胞内の環境やストレスを非侵襲的かつ継続的に可視化できる。
そのため、光を利用した分子イメージングによって、癌の発現や転移だけでなく幹細胞の分化段階における細胞の機能情報や組織への集積について詳細に評価できる。
In this way, bioimaging methods that use light can not only capture the temporal and quantitative dynamics and localization of target molecules, but also non-invasively and continuously visualize not only molecular expression and function, but also the intracellular environment and stress.
Therefore, molecular imaging using light can be used to make detailed assessments of not only cancer onset and metastasis, but also cell function information and accumulation in tissues during stem cell differentiation.
しかし、光計測技術は全身画像の取得を苦手としており、癌細胞や幹細胞の生理的情報と体内での位置を一度に診断することが困難であるため、磁気共鳴画像（ＭＲＩ）による全身画像による解剖学的情報を加味しなければ、癌の有無やその正確な形状や体内での位置を診断することは困難である。 However, optical measurement technology has difficulty obtaining whole-body images, making it difficult to simultaneously diagnose the physiological information of cancer cells and stem cells and their location within the body. Therefore, it is difficult to diagnose the presence or absence of cancer, as well as its exact shape and location within the body, without taking into account anatomical information from whole-body images obtained by magnetic resonance imaging (MRI).
そこで、本発明者は、単一の分子プローブで蛍光イメージングとＭＲＩを組み合わせたマルチモーダルな画像計測法を確立することに着目した。
なお、癌などの疾患の正確な検出、特性決定、モニタリング及び処置を可能にする蛍光シリカ系ナノ粒子を提出するものは知られている（特許文献４）。
特許文献４には、蛍光シリカ系ナノ粒子に磁気特性を持つイオンをコンジュゲートされ得る点が記載されているが、その詳細は明らかではなく少なくとも単一の材料ではない。
Therefore, the present inventors focused on establishing a multimodal imaging and measurement method that combines fluorescence imaging and MRI using a single molecular probe.
It is known that fluorescent silica-based nanoparticles have been proposed that enable accurate detection, characterization, monitoring and treatment of diseases such as cancer (Patent Document 4).
Patent Document 4 describes that ions having magnetic properties can be conjugated to fluorescent silica-based nanoparticles, but the details are not clear, and at least it is not a single material.
本発明の目的とするところは、単一の材料で近赤外領域に蛍光特性と磁気特性を同時に有する白金ナノ粒子含有組成物の製造方法の製造方法を提供することにある。 The object of the present invention is to provide a method for producing a platinum nanoparticle-containing composition that simultaneously has fluorescent properties and magnetic properties in the near infrared region using a single material.
上記の目的を達成するために、本発明の白金ナノ粒子含有組成物（１）の製造方法は、氷冷下において白金イオン（２０）と第五乃至第七世代のポリアミドアミンデンドリマー（１０）とを反応させ前記白金イオン（２０）と前記ポリアミドアミンデンドリマー（１０）との間で化学結合を形成させることで、前記ポリアミドアミンデンドリマー（１０）内に前記白金イオン（２０）を取り込ませる結合工程（１００）と、前記白金イオン（２０）を取り込んだポリアミドアミンデンドリマー（１０）をフルクトースで還元することで、前記ポリアミドアミンデンドリマー（１０）内において白金ナノ粒子（３０）を合成する還元工程（２００）と、前記白金ナノ粒子（３０）にＧＡＢＡを反応させて白金ナノ粒子（３０）にアミノ基（４０）を結合させる修飾工程（３００）を備えることを特徴とする。 In order to achieve the above object, the method for producing a platinum nanoparticle-containing composition (1) of the present invention is characterized by comprising a binding step (100) of reacting platinum ions (20) with a fifth to seventh generation polyamidoamine dendrimer (10) under ice cooling to form a chemical bond between the platinum ions (20) and the polyamidoamine dendrimer (10) to incorporate the platinum ions (20) into the polyamidoamine dendrimer (10), a reduction step (200) of synthesizing platinum nanoparticles (30) within the polyamidoamine dendrimer (10) by reducing the polyamidoamine dendrimer (10) into which the platinum ions (20) have been incorporated with fructose, and a modification step (300) of reacting the platinum nanoparticles (30) with GABA to bind amino groups (40) to the platinum nanoparticles (30).
また本発明は、前記ＧＡＢＡは、４－アミノ酪酸であることを特徴とする。 The present invention is also characterized in that the GABA is 4-aminobutyric acid.
また本発明は、氷冷下において白金イオン（２０）と第五乃至第七世代のポリアミドアミンデンドリマー（１０）とを反応させ前記白金イオン（２０）と前記ポリアミドアミンデンドリマー（１０）との間で化学結合を形成させることで、前記ポリアミドアミンデンドリマー（１０）内に前記白金イオン（２０）を取り込ませる結合工程（１００）と、前記白金イオン（２０）を取り込んだポリアミドアミンデンドリマー（１０）をフルクトースで還元することで、前記ポリアミドアミンデンドリマー（１０）内において白金ナノ粒子（３０）を合成する還元工程（２００）と、前記白金ナノ粒子（３０）にβ－アラニンを反応させて白金ナノ粒子（３０）にアミノ基（４０）を結合させる修飾工程（３００）を備えることを特徴とする。 The present invention is also characterized by comprising a binding step (100) of incorporating the platinum ions (20) into the polyamidoamine dendrimer (10) by reacting the platinum ions (20) with a fifth to seventh generation polyamidoamine dendrimer (10) under ice cooling to form a chemical bond between the platinum ions (20) and the polyamidoamine dendrimer (10); a reduction step (200) of synthesizing platinum nanoparticles (30) within the polyamidoamine dendrimer (10) by reducing the polyamidoamine dendrimer (10) incorporating the platinum ions (20) with fructose; and a modification step (300) of reacting the platinum nanoparticles (30) with β-alanine to bind amino groups (40) to the platinum nanoparticles (30).
また本発明は、得られた前記白金ナノ粒子含有組成物（１）を単離及び精製することを特徴とする。 The present invention is also characterized in that the obtained platinum nanoparticle-containing composition (1) is isolated and purified.
ここで、上記括弧内の記号は、図面および後述する発明を実施するための形態に掲載された対応要素または対応事項を示す。 Here, the symbols in parentheses above indicate the corresponding elements or items shown in the drawings and in the detailed description of the invention described below.
本発明によれば、製造された白金ナノ粒子含有組成物は、近赤外領域において蛍光特性を有するので、放出された光が生体組織に吸収・散乱され難い。したがって、生体の深部（数ｍｍ～数１０ｃｍ）からでも白金ナノ粒子含有組成物の蛍光を１μｍ以下の分解能かつ高感度で観察可能である。
それに加えて、白金ナノ粒子含有組成物は磁気特性を有するものであるので、全身計測可能なＭＲＩを融合させることにより、生体の全身画像の取得が可能となりマルチモーダルな画像計測法を確立することができる。
According to the present invention, the produced platinum nanoparticle-containing composition has fluorescent properties in the near-infrared region, and the emitted light is unlikely to be absorbed or scattered by biological tissue. Therefore, the fluorescence of the platinum nanoparticle-containing composition can be observed with a resolution of 1 μm or less and high sensitivity even from deep inside the body (several mm to several tens of cm).
In addition, since the platinum nanoparticle-containing composition has magnetic properties, by combining it with MRI, which can measure the entire body, it is possible to obtain whole-body images of a living body, establishing a multimodal image measurement method.
これにより、癌の正確な位置を１細胞レベルで特定できるので、初期癌や癌転移の診断が可能となる。また、個体から細胞まで様々なスケールで分子情報を含んだ高精密な生体画像情報を引き出すことが可能となり、生体内における癌発現・癌転移過程の分子機構観察，癌細胞の分化メカニズムの解明や体内追跡など癌治療や再生医療に関する研究を飛躍的に発展することができる。 This allows the exact location of cancer to be pinpointed at the single-cell level, making it possible to diagnose early-stage cancer and cancer metastasis. It also makes it possible to extract highly accurate bioimage information containing molecular information at various scales, from individuals to cells, which will dramatically advance research into cancer treatment and regenerative medicine, such as observing the molecular mechanisms of cancer expression and the cancer metastasis process in vivo, elucidating the differentiation mechanisms of cancer cells, and tracking them in vivo.
また、弱い還元剤であるフルクトースを用いて温和な８０～９０℃の温度下で還元しているので、形成された白金ナノ粒子３０は細胞毒性が低い。特に、白金ナノ粒子含有組成物はそのサイズが１．１ｎｍ～１．５ｎｍと小さいので、生体内に長期間内在させても細胞内へ蓄積され難く、金属の蓄積による細胞毒性が極めて低い。
また、合成に使用した白金は安定で酸化され難いので、生体内での酸化反応によるイオン化及び生成した金属イオンによる生体毒性の発生のリスクが他の金属材料（鉄、コバルト、パラジウム、ニッケル等）による金属ナノ粒子に比べて低い。
In addition, since reduction is performed using fructose, a weak reducing agent, at a mild temperature of 80 to 90° C., the formed platinum nanoparticles 30 have low cytotoxicity. In particular, since the platinum nanoparticle-containing composition has a small size of 1.1 nm to 1.5 nm, it is difficult for the composition to accumulate in cells even if it is left in the body for a long period of time, and cytotoxicity due to metal accumulation is extremely low.
In addition, since the platinum used in the synthesis is stable and difficult to oxidize, the risk of ionization due to oxidation reactions in the body and the occurrence of biotoxicity due to the generated metal ions is lower than that of metal nanoparticles made from other metal materials (iron, cobalt, palladium, nickel, etc.).
このように毒性が低いということは、生体のみならず環境への影響も小さいということでもある。
本発明に係る白金ナノ粒子含有組成物は、太陽電池（ソーラーパネル）にも応用可能である。太陽光には可視光が約５０％、近赤外光が約３０％含まれているが、本発明に係る白金ナノ粒子含有組成物を太陽電池に使用すると、既存の太陽電池がほとんど利用できていない近赤外光も発電に利用できるようになるので、発電効率を飛躍的に向上させることができる。そして、太陽電池等に本発明に係る白金ナノ粒子含有組成物を使用した場合に、故障・破損等による光学物質が漏洩しても環境や人体への影響が小さい。
さらには、化学的に安定しているので、白金ナノ粒子含有組成物を光学物質として半永久的に使用可能である。
Such low toxicity means that it has little impact on not only living organisms but also the environment.
The platinum nanoparticle-containing composition according to the present invention can also be applied to solar cells (solar panels). Sunlight contains about 50% visible light and about 30% near-infrared light. When the platinum nanoparticle-containing composition according to the present invention is used in a solar cell, near-infrared light, which is hardly used by existing solar cells, can also be used for power generation, so that the power generation efficiency can be dramatically improved. Furthermore, when the platinum nanoparticle-containing composition according to the present invention is used in a solar cell, etc., the impact on the environment and human body is small even if the optical material leaks due to failure, breakage, etc.
Furthermore, because the platinum nanoparticle-containing composition is chemically stable, it can be used semi-permanently as an optical material.
長時間観察に使用しても退色せずその輝度（明るさ）が維持され、また白金ナノ粒子含有組成物を室温で半年以上保管してもその光学特性は維持できているので、経過観察が必要な検査や診断に使用可能である。例えば、癌の転移の検査等に有益である。他には、幹細胞を標識し、生体組織へ移植後に長期間経過観察することで、生体内での幹細胞の挙動（移動）や分化・増殖・再生などの過程を評価することができることから、幹細胞による生体組織の再生や治療の過程を可視化・診断できる。 Even when used for long-term observation, the luminance (brightness) is maintained without fading, and the optical properties are maintained even when the platinum nanoparticle-containing composition is stored at room temperature for more than six months, so it can be used for examinations and diagnoses that require follow-up observation. For example, it is useful for examinations of cancer metastasis. In addition, by labeling stem cells and transplanting them into living tissue and observing them for a long period of time, it is possible to evaluate the behavior (migration) of stem cells in the body and the processes of differentiation, proliferation, regeneration, etc., and therefore it is possible to visualize and diagnose the process of regeneration and treatment of living tissue by stem cells.
なお、本発明のように、単一の材料で近赤外領域に蛍光特性と磁気特性を同時に有する白金ナノ粒子含有組成物の製造方法について、上述した特許文献１乃至４には全く記載されていない。 The above-mentioned Patent Documents 1 to 4 do not describe at all a method for producing a platinum nanoparticle-containing composition that simultaneously has fluorescent properties and magnetic properties in the near-infrared region from a single material, as in the present invention.
図１乃至図４を参照して、本発明の実施形態に係る白金ナノ粒子含有組成物１の製造方法を説明する。
この白金ナノ粒子含有組成物１の製造方法は、結合工程１００と、還元工程２００と、修飾工程３００と、単離工程を備える。
A method for producing a platinum nanoparticle-containing composition 1 according to an embodiment of the present invention will be described with reference to FIGS.
The method for producing the platinum nanoparticle-containing composition 1 includes a binding step 100, a reduction step 200, a modification step 300, and an isolation step.
結合工程１００では、ガラス製のスクリュー管（１０ｍＬ）に超純水５ｍＬ加えてから、氷冷下（４℃）で鋳型分子である第五世代のポリアミドアミンデンドリマー１０（ＰＡＭＡＭ Ｇ５－ＯＨ）０．２５μｍｏｌへ、ヘキサクロロ白金（ＩＶ）酸六水和物（Ｈ2ＰｔＣｌ6・６Ｈ2Ｏ）（０．５Ｍ）を９０μＬ加え、そのまま５日間反応させた。
このように低温下で反応させることで、図１に示すように、白金イオン２０がポリアミドアミンデンドリマー１０内により多く取り込まれるので、次工程となる還元工程２００における合成効率が高くなる。
In the bonding step 100, 5 mL of ultrapure water was added to a glass screw tube (10 mL), and then 90 μL of hexachloroplatinic acid (IV) hexahydrate (H 2 PtCl 6.6H 2 O) (0.5 M) was added to 0.25 μmol of the fifth-generation polyamidoamine dendrimer 10 (PAMAM G5-OH) serving as a template molecule under ice cooling (4° C.), and the mixture was allowed to react for 5 days.
By carrying out the reaction at such a low temperature, as shown in FIG. 1, a larger amount of platinum ions 20 are incorporated into the polyamidoamine dendrimer 10, thereby increasing the efficiency of synthesis in the next reduction step 200.
次に還元工程２００では、１Ｍの濃度で調整したフルクトース（Ｄ－Ｆｒｕｃｔｏｓｅ）を白金イオン２０に対してモル比を基準として５０倍（５０：１）となるように加え、８０～９０℃の温度下で２週間還元反応させた。
これにより、図２に示したように、ポリアミドアミンデンドリマー１０内において白金ナノ粒子３０が合成される。
Next, in the reduction step 200, fructose (D-fructose) adjusted to a concentration of 1 M was added to platinum ions 20 in a molar ratio of 50 times (50:1), and the reduction reaction was carried out at a temperature of 80 to 90° C. for two weeks.
As a result, platinum nanoparticles 30 are synthesized within the polyamidoamine dendrimer 10 as shown in FIG.
次に修飾工程３００では、常温（２０～２５℃）において、ＧＡＢＡ５０の中で４－アミノ酪酸を白金ナノ粒子３０に対してモル比を基準として１００倍（１００：１）となるように加えた後、冷暗所で１週間反応させた。
これにより、図３に示したように、白金ナノ粒子３０の周りにアミノ基（ＮＨ2）が結合した白金ナノ粒子含有組成物１が得られる。白金ナノ粒子含有組成物１のモル濃度は、３２４．９ｐｍｏｌ（ピコモル）であった。
Next, in the modification step 300, 4-aminobutyric acid was added to GABA 50 at a molar ratio of 100 times (100:1) the platinum nanoparticles 30 at room temperature (20 to 25° C.), and the mixture was allowed to react in a cool, dark place for one week.
3, a platinum nanoparticle-containing composition 1 is obtained in which amino groups (NH 2 ) are bound around platinum nanoparticles 30. The molar concentration of platinum nanoparticle-containing composition 1 was 324.9 pmol (picomole).
最後に単離工程では、超遠心分離機及び近赤外蛍光検出器を備えた高速液体クロマトグラフ（ＨＰＬＣ）を使用して不純物を取り除き、白金ナノ粒子含有組成物１を単離及び精製を行う。 Finally, in the isolation process, impurities are removed using an ultracentrifuge and a high performance liquid chromatograph (HPLC) equipped with a near-infrared fluorescence detector, and the platinum nanoparticle-containing composition 1 is isolated and purified.
このように生成した白金ナノ粒子含有組成物１に対して励起光として５３５ｎｍの波長の光を照射したとき、図４に示すように発光波長が６３０ｎｍの赤色蛍光（近赤外光）を観測できた。
また、本実施形態に係る白金ナノ粒子３０の粒子径は１．１～１．５ｎｍ、量子収率が０．５％であることもわかった。
When the platinum nanoparticle-containing composition 1 thus produced was irradiated with light having a wavelength of 535 nm as excitation light, red fluorescence (near-infrared light) having an emission wavelength of 630 nm was observed, as shown in FIG.
It was also found that the particle diameter of the platinum nanoparticles 30 according to this embodiment was 1.1 to 1.5 nm, and the quantum yield was 0.5%.
なお、第一乃至第三世代のポリアミドアミンデンドリマー１０を使用して白金ナノ粒子含有組成物１を生成した場合、この白金ナノ粒子含有組成物１は蛍光性を示さなかった。
一方、第四世代のポリアミドアミンデンドリマー１０を使用して白金ナノ粒子含有組成物１を生成した場合、緑色蛍光性（発光波長：５２０ｎｍ）を有するものであった。
When the platinum nanoparticle-containing composition 1 was produced using the first to third generation polyamidoamine dendrimers 10, the platinum nanoparticle-containing composition 1 did not exhibit fluorescence.
On the other hand, when the platinum nanoparticle-containing composition 1 was produced using the fourth-generation polyamidoamine dendrimer 10, it had green fluorescence (emission wavelength: 520 nm).
一般的に、金属ナノ粒子の粒子半径が小さくなるほど、発光波長は青色（短波長）側へシフトすること、また世代の大きなデンドリマーを使用することで金属ナノ粒子の粒子径を大きくすることができること、及び以上の結果より、第五世代以上のポリアミドアミンデンドリマー１０を使用して生成された白金ナノ粒子含有組成物１が赤色蛍光性を有することがわかる。
ここで、従来の赤く光る金属ナノ粒子の粒子径は２．３ｎｍ程度であることが知られているが、本実施形態に係る白金ナノ粒子３０はこれの約半分の大きさであることもわかった。
Generally, the smaller the particle radius of the metal nanoparticles, the more the emission wavelength shifts to the blue (shorter wavelength) side. Also, the particle size of the metal nanoparticles can be increased by using a dendrimer of a larger generation. From the above results, it can be seen that the platinum nanoparticle-containing composition 1 produced using polyamidoamine dendrimer 10 of fifth generation or higher has red fluorescence.
Here, it is known that the particle diameter of conventional red-glowing metal nanoparticles is about 2.3 nm, but it was also found that the platinum nanoparticles 30 according to this embodiment are about half this size.
また、生成された白金ナノ粒子含有組成物１に対して磁場をかけた場合、図５に示すように、白金ナノ粒子含有組成物１は磁気的に正極と負極に分極して磁化されることが観測された。横軸の磁界に対して縦軸は磁化を示し、磁化は飽和しているときに大体１になるように規格化したものである。
また、図６に示したものは、修飾工程３００において、ＧＡＢＡの中で４－アミノ酪酸を白金ナノ粒子３０に対してモル比を基準として５０倍（５０：１）となるように加えたものであり、白金ナノ粒子含有組成物１は明確に磁化されていることがわかる。なお、白金ナノ粒子含有組成物１のモル濃度は、１９５．８ｐｍｏｌ（ピコモル）であった。
In addition, when a magnetic field was applied to the produced platinum nanoparticle-containing composition 1, it was observed that the platinum nanoparticle-containing composition 1 was magnetically polarized and magnetized into positive and negative poles, as shown in Figure 5. The horizontal axis indicates the magnetic field, while the vertical axis indicates the magnetization, which is normalized to be approximately 1 when saturated.
6 shows that in the modification step 300, 4-aminobutyric acid was added to GABA at a molar ratio of 50 times (50:1) the platinum nanoparticles 30, and it can be seen that the platinum nanoparticle-containing composition 1 was clearly magnetized. The molar concentration of the platinum nanoparticle-containing composition 1 was 195.8 pmol (picomole).
これにより、生成された白金ナノ粒子含有組成物１は、単一の材料で、近赤外領域に蛍光特性を有するとともに、磁気特性を同時に有することが確認された。 This confirmed that the platinum nanoparticle-containing composition 1 produced is a single material that simultaneously has fluorescent properties in the near-infrared region and magnetic properties.
なお、癌細胞に対して白金ナノ粒子含有組成物１が蛍光プローブ及び磁気プローブとして有用であることが確認でき、かつこの蛍光プローブ及び磁気プローブとして機能させるために必要な白金ナノ粒子３０の濃度において、白金ナノ粒子３０は生体に使用可能な程度に十分毒性が低いことも確認できた。 It was also confirmed that platinum nanoparticle-containing composition 1 is useful as a fluorescent probe and a magnetic probe for cancer cells, and that at the concentration of platinum nanoparticles 30 required to function as this fluorescent probe and magnetic probe, the toxicity of platinum nanoparticles 30 is sufficiently low that they can be used in living organisms.
以上のように製造された白金ナノ粒子含有組成物１によれば、近赤外領域において蛍光特性を有するので、放出された光が生体組織に吸収・散乱され難い。したがって、生体の深部（数ｍｍ～数１０ｃｍ）からでも白金ナノ粒子含有組成物１の蛍光を１μｍ以下の分解能かつ高感度で観察可能である。
それに加えて、白金ナノ粒子含有組成物１は磁気特性を有するものであるので、全身計測可能なＭＲＩを融合させることにより、生体の全身画像の取得が可能となりマルチモーダルな画像計測法を確立することができる。
The platinum nanoparticle-containing composition 1 produced as described above has fluorescent properties in the near infrared region, so the emitted light is unlikely to be absorbed or scattered by biological tissues. Therefore, the fluorescence of the platinum nanoparticle-containing composition 1 can be observed with a resolution of 1 μm or less and high sensitivity even from deep inside the body (several mm to several tens of cm).
In addition, since the platinum nanoparticle-containing composition 1 has magnetic properties, by combining it with MRI, which can measure the entire body, it is possible to obtain whole-body images of a living body, thereby establishing a multimodal image measurement method.
これにより、癌の正確な位置を１細胞レベルで特定できるので、初期癌や癌転移の診断が可能となる。また、個体から細胞まで様々なスケールで分子情報を含んだ高精密な生体画像情報を引き出すことが可能となり、生体内における癌発現・癌転移過程の分子機構観察，癌細胞の分化メカニズムの解明や体内追跡など癌治療や再生医療に関する研究を飛躍的に発展することができる。 This allows the exact location of cancer to be pinpointed at the single-cell level, making it possible to diagnose early-stage cancer and cancer metastasis. It also makes it possible to extract highly accurate bioimage information containing molecular information at various scales, from individuals to cells, which will dramatically advance research into cancer treatment and regenerative medicine, such as observing the molecular mechanisms of cancer expression and the cancer metastasis process in vivo, elucidating the differentiation mechanisms of cancer cells, and tracking them in vivo.
また、弱い還元剤であるフルクトースを用いて温和な８０～９０℃の温度下で還元しているので、形成された白金ナノ粒子３０は細胞毒性が低い。特に、本実施形態に係る白金ナノ粒子含有組成物１はそのサイズが１．１ｎｍ～１．５ｎｍと小さいので、生体内に長期間内在させても細胞内へ蓄積され難く、金属の蓄積による細胞毒性が極めて低い。
また、合成に使用した白金は安定で酸化され難いので、生体内での酸化反応によるイオン化及び生成した金属イオンによる生体毒性の発生のリスクが他の金属材料（鉄、コバルト、パラジウム、ニッケル等）による金属ナノ粒子に比べて低い。
In addition, since reduction is performed using fructose, a weak reducing agent, at a mild temperature of 80 to 90° C., the formed platinum nanoparticles 30 have low cytotoxicity. In particular, since the platinum nanoparticle-containing composition 1 according to this embodiment has a small size of 1.1 nm to 1.5 nm, it is difficult for the platinum nanoparticles to accumulate in cells even if the platinum nanoparticles are present in the body for a long period of time, and the cytotoxicity due to metal accumulation is extremely low.
In addition, since the platinum used in the synthesis is stable and difficult to oxidize, the risk of ionization due to oxidation reactions in the body and of biotoxicity due to the generated metal ions is lower than that of metal nanoparticles made from other metal materials (iron, cobalt, palladium, nickel, etc.).
さらに、長時間観察に使用しても退色せずその輝度（明るさ）が維持され、また白金ナノ粒子含有組成物１を室温で半年以上保管してもその光学特性は維持できているので、経過観察が必要な検査や診断に使用可能である。例えば、癌の転移の検査等に有益である。他には、幹細胞を標識し、生体組織へ移植後に長期間経過観察することで、生体内での幹細胞の挙動（移動）や分化・増殖・再生などの過程を評価することができることから、幹細胞による生体組織の再生や治療の過程を可視化・診断できる。 Furthermore, even when used for long-term observation, the luminance (brightness) is maintained without fading, and the platinum nanoparticle-containing composition 1 maintains its optical properties even when stored at room temperature for more than six months, making it suitable for use in tests and diagnoses that require follow-up observation. For example, it is useful for testing cancer metastasis. In addition, by labeling stem cells and transplanting them into living tissue and observing them over a long period of time, it is possible to evaluate the behavior (migration) of stem cells in the body and the processes of differentiation, proliferation, regeneration, etc., making it possible to visualize and diagnose the process of regeneration and treatment of living tissue by stem cells.
なお、本実施形態では、修飾工程３００において、常温（２０～２５℃）において、ＧＡＢＡの中で４－アミノ酪酸を白金ナノ粒子３０に対してモル比を基準として１００倍（１００：１）となるように加えた後、冷暗所で１週間反応させたものであるが、４－アミノ酪酸にかえてβ－アラニンを使用することもできる。すなわち、修飾工程３００において、常温（２０～２５℃）において、β－アラニンを白金ナノ粒子３０に対してモル比を基準として１００倍（１００：１）となるように加えた後、冷暗所で１週間反応させるようにしてもよい。これによっても、白金ナノ粒子３０の周りにアミノ基（ＮＨ2）が結合した白金ナノ粒子含有組成物１が得られる。白金ナノ粒子含有組成物１のモル濃度は、９４．３ｐｍｏｌ（ピコモル）であった。 In this embodiment, in the modification step 300, 4-aminobutyric acid is added to GABA at room temperature (20 to 25° C.) so that the molar ratio is 100 times (100:1) based on the platinum nanoparticles 30, and then the mixture is allowed to react in a cool, dark place for one week. However, β-alanine can be used instead of 4-aminobutyric acid . That is, in the modification step 300, β-alanine can be added to platinum nanoparticles 30 at room temperature (20 to 25° C.) so that the molar ratio is 100 times (100:1) based on the platinum nanoparticles 30, and then the mixture is allowed to react in a cool, dark place for one week. This also provides a platinum nanoparticle-containing composition 1 in which an amino group (NH 2 ) is bound around the platinum nanoparticles 30. The molar concentration of the platinum nanoparticle-containing composition 1 was 94.3 pmol (picomole).
このとき、β－アラニンを使用して生成された白金ナノ粒子含有組成物１に対して磁場をかけた場合、図７に示すように、白金ナノ粒子含有組成物１は磁気的に微小ではあるが正極と負極に分極して磁化されることが観測された。横軸の磁界に対して縦軸は磁化を生データの形で示したものである。
また、図８に示したものは、修飾工程３００において、β－アラニンを白金ナノ粒子３０に対してモル比を基準として５０倍（５０：１）となるように加えたものであり、白金ナノ粒子含有組成物１は微小ではあるが磁化されていることがわかる。なお、白金ナノ粒子含有組成物１のモル濃度は、３６．４ｐｍｏｌ（ピコモル）であった。
In this case, when a magnetic field was applied to the platinum nanoparticle-containing composition 1 produced using β-alanine, it was observed that the platinum nanoparticle-containing composition 1 was magnetized by polarizing to the positive and negative poles, although the amount was very small, as shown in Figure 7. The horizontal axis shows the magnetic field, while the vertical axis shows magnetization in the form of raw data.
8 shows that β-alanine was added in the modification step 300 at a molar ratio of 50 times (50:1) the platinum nanoparticles 30, and that the platinum nanoparticle-containing composition 1 was magnetized, although the amount was very small. The molar concentration of the platinum nanoparticle-containing composition 1 was 36.4 pmol (picomole).
これにより、β－アラニンを使用して生成された白金ナノ粒子含有組成物１は、ＧＡＢＡの中で４－アミノ酪酸を使用して生成された白金ナノ粒子含有組成物１と同様に、単一の材料で、近赤外領域に蛍光特性を有するとともに、磁気特性を同時に有することが確認され、ＧＡＢＡの中で４－アミノ酪酸を使用して生成された白金ナノ粒子含有組成物１と同様の効果を有するものであった。 As a result, it was confirmed that platinum nanoparticle-containing composition 1 produced using β-alanine, like platinum nanoparticle-containing composition 1 produced using 4-aminobutyric acid in GABA , is a single material that simultaneously has fluorescent properties in the near-infrared region and magnetic properties, and has the same effects as platinum nanoparticle-containing composition 1 produced using 4-aminobutyric acid in GABA .
また、本実施形態では還元工程２００を８０～９０℃の温度下で行ったが、これに限られるものではなく、７０～９０℃であればよい。 In this embodiment, the reduction process 200 was carried out at a temperature of 80 to 90°C, but this is not limited and any temperature between 70 and 90°C will suffice.
１ 白金ナノ粒子含有組成物
１０ ポリアミドアミンデンドリマー
２０ 白金イオン
３０ 白金ナノ粒子
４０ アミノ基
１００ 結合工程
２００ 還元工程
３００ 修飾工程
1 Platinum nanoparticle-containing composition 10 Polyamidoamine dendrimer 20 Platinum ion 30 Platinum nanoparticle 40 Amino group 100 Bonding step 200 Reduction step 300 Modification step
Claims (4)
前記白金イオンを取り込んだポリアミドアミンデンドリマーをフルクトースで還元することで、前記ポリアミドアミンデンドリマー内において白金ナノ粒子を合成する還元工程と、
前記白金ナノ粒子にＧＡＢＡを反応させて白金ナノ粒子にアミノ基を結合させる修飾工程を備えることを特徴とする白金ナノ粒子含有組成物の製造方法。 a bonding step of reacting platinum ions with a fifth to seventh generation polyamidoamine dendrimer under ice cooling to form a chemical bond between the platinum ions and the polyamidoamine dendrimer, thereby incorporating the platinum ions into the polyamidoamine dendrimer;
a reduction step of synthesizing platinum nanoparticles within the polyamidoamine dendrimer by reducing the polyamidoamine dendrimer having the platinum ions incorporated therein with fructose;
A method for producing a platinum nanoparticle-containing composition, comprising a modification step of reacting the platinum nanoparticles with GABA to bond amino groups to the platinum nanoparticles.
前記白金イオンを取り込んだポリアミドアミンデンドリマーをフルクトースで還元することで、前記ポリアミドアミンデンドリマー内において白金ナノ粒子を合成する還元工程と、
前記白金ナノ粒子にβ－アラニンを反応させて白金ナノ粒子にアミノ基を結合させる修飾工程を備えることを特徴とする白金ナノ粒子含有組成物の製造方法。 a bonding step of reacting platinum ions with a fifth to seventh generation polyamidoamine dendrimer under ice cooling to form a chemical bond between the platinum ions and the polyamidoamine dendrimer, thereby incorporating the platinum ions into the polyamidoamine dendrimer;
a reduction step of synthesizing platinum nanoparticles within the polyamidoamine dendrimer by reducing the polyamidoamine dendrimer having the platinum ions incorporated therein with fructose;
A method for producing a platinum nanoparticle-containing composition, comprising a modification step of reacting the platinum nanoparticles with β-alanine to bind amino groups to the platinum nanoparticles.
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| JP2017002336A (en) | 2015-06-04 | 2017-01-05 | 独立行政法人国立高等専門学校機構 | Platinum nanoparticle-containing composition, platinum nanoparticle and manufacturing method therefor |
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| JP2017002336A (en) | 2015-06-04 | 2017-01-05 | 独立行政法人国立高等専門学校機構 | Platinum nanoparticle-containing composition, platinum nanoparticle and manufacturing method therefor |
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