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Phototherapy nano preparation based on chemical cross-linking as well as preparation method and application thereof

A nano-preparation and chemical cross-linking technology, which is applied in the field of nano-materials and biology, can solve the problems of short lifetime of singlet oxygen, accelerated cell necrosis, and limited action distance, and achieve good structural stability, good tumor imaging, and drug loading high effect

Active Publication Date: 2017-06-27
SOUTHEAST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, singlet oxygen has a short lifetime and a limited action distance, so its anticancer efficacy largely depends on the endocytic efficiency and subcellular localization of photosensitizers.
Generally speaking, photodynamic therapy targeting mitochondria and endoplasmic reticulum and other organelles is more effective. Phototherapy acting on cell membranes can accelerate cell necrosis, while phototherapy targeting lysosomes and other organelles is relatively less effective.

Method used

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  • Phototherapy nano preparation based on chemical cross-linking as well as preparation method and application thereof
  • Phototherapy nano preparation based on chemical cross-linking as well as preparation method and application thereof
  • Phototherapy nano preparation based on chemical cross-linking as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] The synthesis process of POSS-Ce6-PEG is as follows (see the schematic diagram in figure 1 ):

[0052] (1) First, Ce6, EDC and NHS were used as raw materials to activate the carboxyl group of Ce6 molecule. Weigh 10 mg Ce6, 26.0 mg EDC and 28.9 mg NHS and dissolve them in 1 mL DMSO respectively. Ce6 is mixed with EDC first and then NHS is added to react at room temperature (20-25°C in this article) for 4 hours to fully activate the carboxyl group.

[0053] (2) Weigh 6.55 mg of octaaminopropyl hexahedral silsesquioxane (POSS) according to the molar ratio of octaaminopropyl hexahedral silsesquioxane to Ce6 of 1:3, according to the molar ratio of POSS to triethylamine 18.57 μL triethylamine was co-dissolved in DMSO at a ratio of 1:24, mixed with the above reaction system, and reacted overnight at room temperature.

[0054] (3) According to the molar ratio of POSS and NHS-PEG-OMe (where the molecular weight of PEG is 2000) is 1:5, weigh 58.6 mg of NHS-PEG-OMe and dissolve ...

Embodiment 2-4

[0056] The preparation steps of the phototherapy nano-preparation in Example 2 are the same as in Example 1, except that the molar ratio of POSS to Ce6 in step (2) is 1:0.5.

[0057] The preparation steps of the phototherapy nano-preparation in Example 3 are the same as in Example 1, except that the molar ratio of POSS to Ce6 in step (2) is 1:4.

[0058] The preparation steps of the phototherapy nano-preparation in Example 4 are the same as in Example 1, except that the molar ratio of POSS to Ce6 in step (2) is 1:7.

Embodiment 5-7

[0060] The preparation steps of the phototherapy nano-preparation in Example 5 are the same as in Example 1, except that the reaction time between POSS and Ce6 in step (2) is 4 hours.

[0061] The preparation steps of the phototherapy nano-preparation in Example 6 are the same as in Example 1, except that the reaction time between POSS and Ce6 in step (2) is 8 hours.

[0062] The preparation steps of the phototherapy nano-preparation in Example 7 are the same as in Example 1, except that the reaction time between POSS and Ce6 in step (2) is 12 hours.

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Abstract

The invention discloses a preparation method and application of a novel phototherapy nano preparation based on polyhedral oligomeric silsesquioxane (POSS). The phototherapy nano preparation is prepared by forming nano particles by chemical cross-linking reaction between amino of the POSS and carboxyl of a photosensitizer and then performing surface pegylation. The nano preparation has the benefits that the photosensitizer is taken as one part by utilizing a chemical cross-linking method, so that the ultra-high drug loading capacity is realized; the advance drug leakage is avoided; a self-quenching effect of the photosensitizer is inhibited. Meanwhile, the drug has good water dispersibility, stability and biosafety. In addition, the phototherapy nano preparation can be endocytosed by cancer cells in large quantities and efficiently kill the cancer cells under light conditions. An in-vivo animal experiment proves that the phototherapy nano preparation can be enriched to a tumor area through passive targeting, so that tumor imaging and photodynamic therapy are realized.

Description

technical field [0001] The invention discloses a preparation method of a novel phototherapy nano-preparation and its application in tumor imaging and photodynamic therapy, belonging to the field of nano-materials and biotechnology. Background technique [0002] Photodynamic therapy is an emerging cancer treatment method, which avoids the shortcomings of traditional treatment methods (such as chemotherapy, radiotherapy and surgical resection) such as strong invasiveness, high systemic toxicity and incomplete treatment, etc. Small tissue damage and no accumulation of drug toxicity. Photodynamic therapy mainly uses the active oxygen molecules generated by photosensitizer molecules under light conditions to kill cancer cells. However, most photosensitizer molecules have poor water solubility and tend to form aggregates in aqueous solution, which greatly inhibits the singlet oxygen yield and therapeutic effect of photosensitizers. [0003] At present, the commonly used strategy...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K47/60A61K41/00A61K49/00A61P35/00
CPCA61K9/0019A61K41/0071A61K49/0054A61K49/0093
Inventor 吴富根祝雅璇贾浩然
Owner SOUTHEAST UNIV
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