Targeted nano-photo drug for photodynamic therapy of cancer

A photodynamic therapy and targeting technology, applied in drug combination, drug delivery, preparations for in vivo tests, etc., can solve the problem of limiting the total dose of active oxygen

Inactive Publication Date: 2015-09-09
ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

This effect limits the total dose of rea

Method used

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  • Targeted nano-photo drug for photodynamic therapy of cancer
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  • Targeted nano-photo drug for photodynamic therapy of cancer

Examples

Experimental program
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Embodiment 1

[0099] Embodiment 1: with Ce 6 Preparation of Nanophotomedicine NPM-1 as Photosensitizer

[0100] In this example, the photosensitizer chlorin e 6 (Ce 6 ) of nanophotomedicine (i.e., NPM-1), the optical absorption of the final structure of the nanophotomedicine in the Q-band (654nm) region is free Ce 6 about 3 times.

[0101] Ce at a concentration of 1 μM in 5 ml of 99% DMSO 6 (commercially available from, eg, Porphyrin Products (Logan, Utah)) was reacted with a 10-15 fold molar excess of EDAC and a 10-15 molar excess of sulfo-NHS. After reacting for 4 hours, the combined product was purified by gel filtration to obtain an ammonia-reactive photosensitizer, which was further reacted with 200 μL of silane coupling agent APTS. The coupling reaction is carried out in the dark at room temperature for 3 to 4 hours to obtain the compound Ce 6 -APTS. In the next step, in 10 ml of 99% ethanol medium, Ce 6 - APTS was reacted with 600 μL (about 600 mg) of TEOS or TMOS for 2-3...

Embodiment 2

[0103] Example 2: With Ce 6 Characteristics of Nanophotopharmaceutical NPM-2 as Photosensitizer

[0104] In this example, the ratio of Q-band light absorption to free Ce 6 Increased nanophotomedicine (NPM-2) process by about 4 times.

[0105] Ce at a concentration of 1 μM in 5 ml of 99% ethanol 6 React with 10-15 times molar excess of EDAC and 10-15 molar excess of sulfo-NHS. After about 4 hours of reaction, the conjugate was purified by gel filtration to obtain an ammonia-reactive photosensitizer, which was reacted with 300 μL of silane coupling agent APTS. The coupling reaction is carried out in the dark at room temperature for 3 to 4 hours to obtain the compound Ce 6 -APTS. In the next step, in 10 ml of 99% ethanol medium, Ce 6 -APTS was reacted with 800 μL of TEOS or TMOS for 3 hours to generate the precursor of NPM-2. Add 3ml of water and 600μL of NH 4 o 4 , at intervals of 2 minutes, ultrasonic treatment was performed for 15 minutes to hydrolyze the precur...

Embodiment 3

[0106] Embodiment 3: with Ce 6 Preparation of Nanophotomedicine NPM-3 as Photosensitizer

[0107] In yet another embodiment, the absorption ratio in the Q-band region is illustrated for free Ce 6 Increased preparation of nanophotomedicine (NPM-3) by approximately 7-fold.

[0108] Ce at a concentration of 1 μM in 5 ml of 99% ethanol 6 React with 10-15 times molar excess of EDAC and 10-15 molar excess of sulfo-NHS. After 4 hours of reaction, the combined product was purified by gel filtration to obtain ammonia-reactive Ce 6 , ammonia-reactive Ce 6 React with 600 μL of silane coupling reagent APTS. The coupling reaction is carried out in the dark at room temperature for 3 to 4 hours to obtain the compound Ce 6 -APTS. In the next step, in 10 ml of 99% ethanol medium, Ce 6 -APTS was reacted with 1000 μL of TEOS or TMOS for 2-3 hours to form a precursor of silane-coupled quasi-aggregated photopharmaceuticals. Add 3ml of water and 800μL of NH 4 o 4 , sonicated for 20...

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Abstract

The invention relates to a nano-particle containing a photosensitizer. The nano-particle comprises the photosensitizer, wherein the photosensitizer is combined to a nano-particle matrix material through at least part of nano-particle covalent bonds and merged into the nano-particle matrix in a quasi aggregation state. The invention further relates to a method for preparing the nano-particle and a method for killing cancer cells through photodynamic therapy using the nano-particles.

Description

[0001] This application is a divisional application submitted on February 13, 2012 with the application number 200980160922.6 and the title of the invention is "Targeted Nanophotomedicine for Photodynamic Therapy of Cancer". technical field [0002] The present invention relates to cancer treatment and therapeutic formulations for cancer treatment. In particular, the present invention relates to nanomedicines for photodynamic therapy of cancer, and methods of preparing said nanomedicines. Background technique [0003] Photodynamic therapy (PDT) is an emerging therapeutic modality for the treatment of many types of cancer and various non-malignant diseases. In photodynamic therapy, photoactivation of photosensitizing drugs can generate reactive oxygen species (Reactive Oxygen Species, ROS), such as: singlet oxygen ( 1 o 2 ), oxygen free radicals or peroxides, these reactive oxygen species can oxidatively damage cellular compartments including plasma, mitochondria, lysosomes...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/14A61K47/48A61K49/00A61K49/18A61P35/00
Inventor M·科亚库蒂多米尼克·詹姆斯·罗宾逊亨利克斯·约翰尼斯·科尼利厄斯·玛丽亚·斯提伦伯格S·卡斯卡科瓦珊提库玛尔·奈尔
Owner ERASMUS UNIV MEDICAL CENT ROTTERDAM ERASMUS MC
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