RU2011152596A - Полимерные наночастицы, покрытые оксидом магнитного металла, и их применение - Google Patents

Полимерные наночастицы, покрытые оксидом магнитного металла, и их применение Download PDF

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RU2011152596A
RU2011152596A RU2011152596/15A RU2011152596A RU2011152596A RU 2011152596 A RU2011152596 A RU 2011152596A RU 2011152596/15 A RU2011152596/15 A RU 2011152596/15A RU 2011152596 A RU2011152596 A RU 2011152596A RU 2011152596 A RU2011152596 A RU 2011152596A
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nanoparticle
agent
active agent
specified
peptide
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Шломо МАРДЖЕЛ
Бенни ПЕРЛШТЕЙН
Чая БРОУДИ
Том Миккелсен
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Бар-Илан Юниверсити
Генри Форд Хоспитал
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Abstract

1. Наночастица, содержащая полимер, хелатирующий металл, оксид магнитного металла и, по меньшей мере, одно активное средство, ковалентно связанное с указанным полимером.2. Наночастица по п.1, где указанный полимер, хелатирующий металл, представляет собой желатин, полиметиленимин, хитозан или полилизин.3. Наночастица по п.1, где указанный оксид магнитного металла представляет собой оксид железа или феррит, происходящий из оксида железа.4. Наночастица по п.3, где указанный оксид железа представляет собой магнетит, оксимагнетит или их смесь.5. Наночастица по п.1, где указанное, по меньшей мере, одно активное средство представляет собой флуоресцентный краситель, контрастное средство, пептид или пептидомиметик, полипептид, антифолатное лекарственное средство, антибиотик, противовоспалительное средство, химиотерапевтическое средство антрациклинового ряда или любую их комбинацию.6. Наночастица по п.5, где указанный флуоресцентный краситель представляет собой родамин или флуоресцеин.7. Наночастица по п.5, где указанный пептид или пептидомиметик представляют собой циклический RGD (cRGD) или ациклический RGD.8. Наночастица по п.5, где указанный полипептид представляет собой родственный TNF лиганд, индуцирующий апоптоз (TRAIL), или интерлейкин-12 (IL-12).9. Наночастица по п.5, где указанное антифолатное лекарственное средство представляет собой метатрексат.10. Наночастица по п.5, где указанное химиотерапевтическое средство антрациклинового ряда представляет собой доксорубицин.11. Наночастица по п.1, дополнительно включающая, по меньшей мере, одно дополнительное активное средство, связанное с внешней поверхностью указанной наночастицы.12. На�

Claims (27)

1. Наночастица, содержащая полимер, хелатирующий металл, оксид магнитного металла и, по меньшей мере, одно активное средство, ковалентно связанное с указанным полимером.
2. Наночастица по п.1, где указанный полимер, хелатирующий металл, представляет собой желатин, полиметиленимин, хитозан или полилизин.
3. Наночастица по п.1, где указанный оксид магнитного металла представляет собой оксид железа или феррит, происходящий из оксида железа.
4. Наночастица по п.3, где указанный оксид железа представляет собой магнетит, оксимагнетит или их смесь.
5. Наночастица по п.1, где указанное, по меньшей мере, одно активное средство представляет собой флуоресцентный краситель, контрастное средство, пептид или пептидомиметик, полипептид, антифолатное лекарственное средство, антибиотик, противовоспалительное средство, химиотерапевтическое средство антрациклинового ряда или любую их комбинацию.
6. Наночастица по п.5, где указанный флуоресцентный краситель представляет собой родамин или флуоресцеин.
7. Наночастица по п.5, где указанный пептид или пептидомиметик представляют собой циклический RGD (cRGD) или ациклический RGD.
8. Наночастица по п.5, где указанный полипептид представляет собой родственный TNF лиганд, индуцирующий апоптоз (TRAIL), или интерлейкин-12 (IL-12).
9. Наночастица по п.5, где указанное антифолатное лекарственное средство представляет собой метатрексат.
10. Наночастица по п.5, где указанное химиотерапевтическое средство антрациклинового ряда представляет собой доксорубицин.
11. Наночастица по п.1, дополнительно включающая, по меньшей мере, одно дополнительное активное средство, связанное с внешней поверхностью указанной наночастицы.
12. Наночастица по п.11, где указанное, по меньшей мере, одно дополнительное активное средство ковалентно связано с внешней поверхностью наночастицы через линкер.
13. Наночастица по п.12, где указанный линкер происходит из полисахарида, белка, пептида, полиамина, полиэтиленгликоля, акрилоилхлорида, дивинилсульфона (DVS), дикарбонилимидазола, этиленгликоль-бис(сульфосукцинимидилсукцината), N-гидроксисульфосукцинимидного эфира m-малеимидобензойной кислоты или любой их комбинации.
14. Наночастица по п.11, где указанное, по меньшей мере, одно дополнительное активное средство, связанное с внешней поверхностью наночастицы, представляет собой флуоресцентный краситель, контрастное средство, пептид или пептидомиметик, полипептид, антифолатное лекарственное средство, антибиотик, противовоспалительное средство, химиотерапевтическое средство антрациклинового ряда или любую их комбинацию.
15. Наночастица по п.14, где указанный пептид или пептидомиметик представляют собой циклический RGD (cRGD) или ациклический RGD.
16. Наночастица по п.14, где указанный полипептид представляет собой цитокин, фермент, антитело или гормон.
17. Наночастица по п.16, где указанное антитело представляет собой Bevacizumab (торговое наименование: Авастин) или Infliximab (торговое наименование: Ремикад).
18. Наночастица по п.14, где указанный полипептид представляет собой родственный TNF лиганд, индуцирующий апоптоз (TRAIL), или интерлейкин-12 (IL-12).
19. Фармацевтическая композиция, содержащая наночастицу по п.1 и фармацевтически приемлемый носитель.
20. Применение наночастицы по п.1 для обнаружения опухоли у индивидуума, где TRAIL, пептид cRGD, IL-12, доксорубицин, метотрексат или любая их комбинация связаны с внешней поверхностью наночастицы, а контрастное средство или флуоресцентный краситель ковалентно связаны с указанным полимером.
21. Применение наночастицы по п.11 для индуцирования апоптоза, аутофагии или обоих в раковой клетке, где указанноеЮ по меньшей мере, одно активное средство представляет собой TRAIL, пептид cRGD, IL-12, доксорубицин, метотрексат, Bevacizumab или любую их комбинацию, и где указанная раковая клетка представляет собой глиомную клетку, раковую стволовую клетку, клетку карциномы шейки матки, клетку карциномы мочевого пузыря, клетку рака молочной железы, клетку рака яичника или клетку рака легкого.
22. Применение по п.21, где указанное индуцирование апоптоза, аутофагии или обоих в раковой клетке представляет собой лечение пациента, страдающего глиомой, карциномой шейки матки, карциномой мочевого пузыря, раком молочной железы, раком яичника или раком легкого.
23. Применение по п.21, дополнительно включающее стадию приведения указанной клетки в контакт с ингибитором протеосомы.
24. Применение по п.21, дополнительно включающее стадию γ-облучения указанной клетки.
25. Применение наночастицы по п.1 для применения рентгеновской визуализации или магнитно-резонансной визуализации (МРТ) к субъекту, где указанное активное средство представляет собой контрастное средство.
26. Применение наночастицы по п.1 для обнаружения воспаления у субъекта, где указанный оксид магнитного металла представляет собой оксид железа или феррит, а указанное, по меньшей мере, одно активное средство представляет собой флуоресцентный краситель или контрастное средство.
27. Применение наночастицы по п.1 для лечения воспаления у субъекта, где указанный оксид магнитного металла представляет собой оксид железа, а указанное, по меньшей мере, одно активное средство представляет собой противовоспалительное средство.
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