ES2627998T3 - Nanopartículas fluorescentes - Google Patents
Nanopartículas fluorescentes Download PDFInfo
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- ES2627998T3 ES2627998T3 ES05025022.4T ES05025022T ES2627998T3 ES 2627998 T3 ES2627998 T3 ES 2627998T3 ES 05025022 T ES05025022 T ES 05025022T ES 2627998 T3 ES2627998 T3 ES 2627998T3
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- nanoparticles
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/62—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing gallium, indium or thallium
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0065—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle
- A61K49/0067—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the luminescent/fluorescent agent having itself a special physical form, e.g. gold nanoparticle quantum dots, fluorescent nanocrystals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/54—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing zinc or cadmium
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/56—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing sulfur
- C09K11/562—Chalcogenides
- C09K11/565—Chalcogenides with zinc cadmium
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- C—CHEMISTRY; METALLURGY
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- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
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- C09K11/74—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing arsenic, antimony or bismuth
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- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/74—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing arsenic, antimony or bismuth
- C09K11/7442—Aluminates; Silicates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Radiology & Medical Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
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- Endoscopes (AREA)
- Magnetic Resonance Imaging Apparatus (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Nanopartículas fluorescentes que contienen un núcleo inorgánico, una capa de pasivación que contiene un componente de imidazol y ligandos específicos para una molécula diana, con un diámetro hidrodinámico del núcleo inorgánico con la capa de pasivación de no más de 15 nm, preferiblemente de no más de 10 nm, de modo particular preferiblemente de no más de 5 nm, para el uso como marcación en el diagnóstico de tejidos para discriminar diferentes tipos de tejidos en intervenciones quirúrgicas, endoscópicas o mínimamente invasivas, presentando las nanopartículas una emisión inferior a 700 nm.
Description
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La combinación de diámetro hidrodinámico reducido, el cual conduce a las mencionadas elevadas velocidades de difusión y de perfusión, junto con las ya descritas propiedades y mejoramientos y la elevada intensidad de fluorescencia, sobre todo en el intervalo de luz del rojo visible da a las nanopartículas de acuerdo con la invención un diagnóstico sencillo, de múltiples usos para una discriminación selectiva y exacta de formas de tejido in vivo. Estas posibilidades en combinación con marcadores biológicos específicos para tejidos sirven sobre todo para diferenciar tejidos anormales, (pre)cancerosos de tejidos normales, lo cual durante una intervención operativa soporta una evaluación visual para la disección más precisa de tumores. Las nanopartículas que pueden usarse de acuerdo con la invención sirven con ello como agente de contraste.
De acuerdo con la presente invención, las nanopartículas pueden ser usadas bien sea como diagnóstico, teranóstico y/o terapéutico in vitro o in vivo. Para ello pueden administrarse localmente (por ejemplo intratumoral, intramuscular o en tejidos/órganos disponibles para operaciones) o también de modo sistémico (por ejemplo intravenoso). La administración local/tópica puede ser provista como líquido, solución para atomización, gel, espuma, crema, parche activo. Esto puede ser preferido en particular en el tratamiento/diagnóstico de órganos huecos. También es posible una ingestión oral, por ejemplo como jugo o en forma de comprimidos o cápsulas. Igualmente es posible una inhalación (por ejemplo atomizado). Está provista una aplicación anal mediante supositorios. En una variante, las nanopartículas pueden ser implantadas en forma de depósito.
Las nanopartículas pueden ser usadas como diagnóstico sobre todo en intervenciones quirúrgicas. Así mismo, pueden usarse en procedimientos mínimamente invasivos (por ejemplo endoscopia, laparoscopia). Es sensata una combinación con procedimientos que forman imagen como PET, MRT, CT etc.
Pueden ser objetivo de las investigaciones todos los tejidos/órganos disponibles del paciente, sobre todo la piel, órganos huecos (por ejemplo en el tracto gastrointestinal, -urogenital, -respiratorio) o también zonas disponibles externas de los órganos de los sentidos y también el sistema cardiovascular.
También es posible el uso como diagnóstico in vitro, así por ejemplo la inmunohistoquímica o FACS así como ELISA. Es particularmente ventajosa una combinación de diagnóstico in vivo e in vitro (por ejemplo material de biopsia).
En tanto las nanopartículas pueden usarse para propósitos de terapia de acuerdo con la invención, al menos algunos de los ligandos de nanopartículas pueden portar moléculas efectoras o principios activos, es decir representan efectores. Al respecto, un efector es un ligando con una función elegida. De modo ventajoso, las nanopartículas portan tanto ligandos específicos para la localización focalizada de la nanopartícula en el cuerpo o bien en el tejido, como también un ligando con molécula efectora.
El efector puede permanecer unido a las nanopartículas o puede ser escindible o separable o liberable. Por ejemplo, el efector puede ejecutar su función mediante una activación/desactivación de un receptor, un enmascaramiento de estructuras (superficies), la activación del sistema inmune ("cebado"), la modulación de rutas de señal, la activación o inactivación de una enzima, la terapia de genes (por ejemplo mediante suministro dirigido de plásmidos o siARN ), el suministro dirigido de toxinas/quimioterapéuticos/citoestáticos o el efecto estimulante sobre por ejemplo metabolismo, formación de hormonas, entre otros. También es posible la protección de las células, por ejemplo células B que producen insulina.
Ejemplo de realización:
Experimento in vivo: experimento animal con tumores xenoinjertos HT29 en ratones imberbes con inyección intratumoral de complejos anticuerpo de acuerdo con la invención
En un experimento in vivo en ratones con tumores xenoinjertos se mostró una "diana de tumor" específico de conjugados de anticuerpo de acuerdo con la invención. Para ello en ratones imberbes (sin timo y por ello inmunosuprimidos) se inyectaron de modo subcutáneo células cancerosas de intestino grueso humano de la línea de células HT29, que formaron tumores sólidos después de un periodo de crecimiento de 3 semanas.
Para una marcación selectiva del tumor se preparó un complejo de anticuerpo de acuerdo con la invención, o bien un conjugado de neutravidina de acuerdo con la invención, con un anticuerpo monoclonal biotinilado unido a él. Este anticuerpo monoclonal está dirigido contra el transportador de glucosa 1 (GLUT1) de antígeno asociado con tumor ubicado en la membrana, el cual se expresa en muchas formas de carcinoma colorectal humano.
Después de inyección intratumoral de los complejos, los tumores fueron reconocidos visualmente ya bajo excitación UV fluorescente roja. Después de hasta 48 h luego de inyección pudieron detectarse los complejos de acuerdo con la invención en criocortes producidos de los tumores.
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Claims (1)
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imagen1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05025022.4A EP1787659B1 (de) | 2005-11-16 | 2005-11-16 | Fluoreszenz-Nanopartikel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2627998T3 true ES2627998T3 (es) | 2017-08-01 |
Family
ID=37752631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES05025022.4T Active ES2627998T3 (es) | 2005-11-16 | 2005-11-16 | Nanopartículas fluorescentes |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US8974767B2 (es) |
| JP (2) | JP5537808B2 (es) |
| KR (1) | KR20080070746A (es) |
| CN (1) | CN101360515B (es) |
| AU (1) | AU2006314773B2 (es) |
| CA (1) | CA2628678C (es) |
| ES (1) | ES2627998T3 (es) |
| HK (1) | HK1129567A1 (es) |
| WO (1) | WO2007057182A2 (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ587438A (en) | 2008-02-29 | 2012-04-27 | Signalomics Gmbh | Optimized adhesin fragments comprising mutated afa/dra adhesions and corresponding nanoparticles |
| EP2329251A1 (en) * | 2008-08-05 | 2011-06-08 | Agency for Science, Technology And Research | Methods, compositions, and articles comprising stabilized gold nanoclusters |
| KR101032307B1 (ko) * | 2008-10-02 | 2011-05-06 | 전북대학교병원 | 생체적합성 분자광학영상용 양자점 및 이의 제조방법 |
| CA2764028A1 (en) * | 2009-06-05 | 2010-12-09 | Institut National D'optique | Hybrid-multimodal magneto-optical contrast marker |
| CN102869749B (zh) * | 2010-04-30 | 2013-11-13 | 海洋王照明科技股份有限公司 | 一种硼酸盐基红色发光材料及其制备方法 |
| CN102366632A (zh) * | 2011-08-22 | 2012-03-07 | 长春工业大学 | 顺磁性金属配合物功能化的荧光金纳米簇磁共振和荧光成像造影剂 |
| WO2013123390A1 (en) * | 2012-02-16 | 2013-08-22 | Qd Vision, Inc. | Method for preparing semiconductor nanocrystals |
| DE102013206077A1 (de) * | 2013-04-05 | 2014-10-09 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Blau-emittierende Leuchtdioden auf Basis von Zinkselenid-Quantenpunkten |
| EP2886126B1 (en) | 2013-12-23 | 2017-06-07 | Exchange Imaging Technologies GmbH | Nanoparticle conjugated to CD44 binding peptides |
| EP3028721A1 (en) * | 2014-12-05 | 2016-06-08 | Exchange Imaging Technologies GmbH | Nanoparticle formulation having reverse-thermal gelation properties for injection |
| JP6683571B2 (ja) * | 2016-08-10 | 2020-04-22 | トヨタ自動車株式会社 | 排ガス浄化触媒 |
| WO2018065860A1 (en) * | 2016-10-04 | 2018-04-12 | Nanoco Technologies Ltd. | Polymerizable quantum dot nanoparticles and their use as therapeutic, ablation and tattooing agents |
| WO2018135434A1 (ja) * | 2017-01-18 | 2018-07-26 | 三菱マテリアル株式会社 | 可視蛍光を発するＣｄを含まないコロイダル量子ドット及びその製造方法 |
| JP2018115315A (ja) * | 2017-01-18 | 2018-07-26 | 三菱マテリアル株式会社 | 可視蛍光を発するＣｄを含まないコロイダル量子ドット及びその製造方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0979107A1 (en) * | 1997-04-29 | 2000-02-16 | Nycomed Imaging As | Light imaging contrast agents |
| US6207392B1 (en) | 1997-11-25 | 2001-03-27 | The Regents Of The University Of California | Semiconductor nanocrystal probes for biological applications and process for making and using such probes |
| US6306610B1 (en) | 1998-09-18 | 2001-10-23 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
| US6179912B1 (en) | 1999-12-20 | 2001-01-30 | Biocrystal Ltd. | Continuous flow process for production of semiconductor nanocrystals |
| US6748259B1 (en) * | 2000-06-15 | 2004-06-08 | Spectros Corporation | Optical imaging of induced signals in vivo under ambient light conditions |
| US20050059031A1 (en) * | 2000-10-06 | 2005-03-17 | Quantum Dot Corporation | Method for enhancing transport of semiconductor nanocrystals across biological membranes |
| US20020127224A1 (en) | 2001-03-02 | 2002-09-12 | James Chen | Use of photoluminescent nanoparticles for photodynamic therapy |
| WO2002072154A1 (de) | 2001-03-08 | 2002-09-19 | Nanosolutions Gmbh | Paramagnetische nanopartikel |
| EP1456022B1 (en) | 2001-09-17 | 2009-11-11 | Life Technologies Corporation | Nanocrystals |
| US7205048B2 (en) * | 2001-09-17 | 2007-04-17 | Invitrogen Corporation | Functionalized fluorescent nanocrystal compositions and methods of making |
| CN100356984C (zh) | 2002-01-24 | 2007-12-26 | 巴内斯－朱威胥医院 | 整联蛋白靶向的影像剂 |
| US7611907B2 (en) | 2002-06-27 | 2009-11-03 | Georgia Tech Research Corporation | Nano-sized optical fluorescence labels and uses thereof |
| US7939170B2 (en) | 2002-08-15 | 2011-05-10 | The Rockefeller University | Water soluble metal and semiconductor nanoparticle complexes |
| US20040101822A1 (en) | 2002-11-26 | 2004-05-27 | Ulrich Wiesner | Fluorescent silica-based nanoparticles |
| CA2524350C (en) | 2003-05-07 | 2015-04-14 | Indiana University Research & Technology Corporation | Alloyed semiconductor quantum dots and concentration-gradient alloyed quantum dots, series comprising the same and methods related thereto |
| AU2003285133A1 (en) | 2003-11-05 | 2005-06-24 | The Government Of The United States Of America As Represented By The Secretary Of Health And Human Services | Biofunctionalized quantum dots for biological imaging |
| JP2005226021A (ja) * | 2004-02-16 | 2005-08-25 | Nihon Medi Physics Co Ltd | マンノース受容体親和性化合物 |
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2005
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2006
- 2006-11-16 AU AU2006314773A patent/AU2006314773B2/en not_active Ceased
- 2006-11-16 WO PCT/EP2006/010996 patent/WO2007057182A2/de active Application Filing
- 2006-11-16 CN CN200680049170.2A patent/CN101360515B/zh not_active Expired - Fee Related
- 2006-11-16 US US12/093,977 patent/US8974767B2/en not_active Expired - Fee Related
- 2006-11-16 JP JP2008540516A patent/JP5537808B2/ja not_active Expired - Fee Related
- 2006-11-16 CA CA2628678A patent/CA2628678C/en not_active Expired - Fee Related
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| AU2006314773A1 (en) | 2007-05-24 |
| CN101360515B (zh) | 2014-03-19 |
| AU2006314773B2 (en) | 2013-04-11 |
| JP5537808B2 (ja) | 2014-07-02 |
| US8974767B2 (en) | 2015-03-10 |
| KR20080070746A (ko) | 2008-07-30 |
| CA2628678A1 (en) | 2007-05-24 |
| JP2013079962A (ja) | 2013-05-02 |
| JP2009516182A (ja) | 2009-04-16 |
| CN101360515A (zh) | 2009-02-04 |
| US20090226371A1 (en) | 2009-09-10 |
| WO2007057182B1 (de) | 2008-04-17 |
| WO2007057182A2 (de) | 2007-05-24 |
| CA2628678C (en) | 2016-01-05 |
| HK1129567A1 (en) | 2009-12-04 |
| WO2007057182A3 (de) | 2008-02-28 |
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