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Tumor targeting photosensitizers and preparation methods and applications of photosensitizers

A photosensitizer and reaction technology, which can be used in antitumor drugs, sexual diseases, pharmaceutical formulations, etc., and can solve problems such as low molar absorbance

Active Publication Date: 2013-10-02
赤峰福纳康生物技术有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these photosensitizers still have deficiencies, such as the first-generation photosensitizers hematoporphyrin derivatives and bis-hematoporphyrin esters, etc., have low molar absorptivity and cannot fully convert light into cytotoxic substances; the second generation Although photosensitizers including 5-aminolevulinic acid (5-ALA) and tin initial porphyrin (SnEtz) overcome this shortcoming, the enrichment effect of these photosensitizers in tumor cells has certain limitations. The content of the agent in the tumor tissue is an important strategy to improve the photodynamic efficacy

Method used

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  • Tumor targeting photosensitizers and preparation methods and applications of photosensitizers
  • Tumor targeting photosensitizers and preparation methods and applications of photosensitizers
  • Tumor targeting photosensitizers and preparation methods and applications of photosensitizers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: HSA-(PpIX) 2 Preparation process of photosensitizer

[0037] figure 1 HSA-(PpIX) 2 Schematic diagram of the preparation process

[0038] 1) Dissolve 100mg HSA in 5mL PBS (pH7.4) buffer solution, directly add 500μL PpIX DMSO solution with a concentration of 10mM in batches, use 0.1M NaOH solution to adjust the pH to about 7, and react at room temperature for 4h;

[0039] 2) After the reaction, use a dialysis bag with MW=12,000-14,000 to remove small molecules by dialysis, and finally use Sephadex G-25 (PD-10 mesh) for further separation and purification, eluent: 0.5M CH 3 COONa (pH=6.0), using a UV-Vis spectrophotometer at 365nm to monitor the absorption spectrum of PpIX in the dialysate in real time to ensure complete purification and obtain HSA-(PpIX) 2 Photosensitizer.

Embodiment 2

[0040] Example 2: HSA-(PpIX) 2 -TF 60 Preparation process of photosensitizer

[0041] figure 2 HSA-(PpIX) 2 -TF 60 Schematic diagram of the preparation process

[0042] a) (C 60 [C(COOH) 2 ] x (x=3), referred to as TF 60 ) Preparation: reference (Bingel, C., Cyclopropanierung von Fullerenen. Chemische Berichte 1993, 126 (8), 1957-1959.) to prepare fullerene carboxylate derivatives, followed by hydrolysis with NaH to obtain fullerene carboxylate derivatives.

[0043] b) 10 mg fullerene carboxylic acid derivative (C 60 [C(COOH) 2 ] x (x=3)) was dissolved in 10mL MES (pH5.5) buffer, added 10mg EDC and 5mg NHS (C 60 [C(COOH) 2 ] x With EDC, NHS molar ratio is 1:6:6), react at room temperature for 2h to get fullerene carboxylic acid active ester.

[0044] c) 10mg HSA-(PpIX) 2 Add it to the above-mentioned fullerene carboxylic acid active ester solution, stir overnight at room temperature, use a dialysis bag with MW=12,000-14,000 to remove small molecules, and then ...

Embodiment 3

[0048] Example 3: Photodynamic effect evaluation of photosensitizer in vivo

[0049] 1. In vitro dark toxicity test of photosensitizer:

[0050] 5x10 4 Hela cells were seeded into a 96-well plate and cultured overnight. After adding a series of concentration gradient samples and incubating the cells for 24 hours, the cytotoxicity was analyzed using WST-8. 10 μl CCK-8 was added to each well, and an enzyme-linked immunosorbent assay was used at a wavelength of 450nm. The light absorbance value can be determined indirectly, which can indirectly reflect the number of living cells.

[0051] The cell viability of samples incubated with HeLa cells for 24h in the concentration range of 0-50μM was as follows: Image 6 As shown, cells without sample and PpIX (dissolved in 2 μL DMSO) treated cells were used as controls. The use of HSA-modified photosensitizers significantly increased the biocompatibility of PpIX without apparent cytotoxicity at a concentration of 50 μM. The addition ...

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Abstract

The invention discloses two tumor targeting photosensitizers, and preparation methods and applications of the photosensitizers. The photosensitizer HSA-(PpIX)2 is prepared by coupling reaction of HSA and PpIX. With the adoption of modification, the biocompatibility and the photochemical property of PpIX are improved; PpIX has stronger killing effect on a cancer cell; and the fluorescence of protoporphyrin is kept. In addition, HSA-(PpIX)2 can be used for adjusting the yield of active oxygen after loading fullerene derivatives. Vivo experiments of mouse breast cancer models indicate that the photosensitizer can be gathered at a tumor site efficiently due to a special EPR effect of a nanomaterial to realize high-sensitive fluorescent imaging of an in vivo level, so that a tumor is positioned accurately, and the best treatment time is monitored. The 16-day monitoring of the effect of photodynamic therapy shows that the photosensitizer can inhibit the growth of the tumor effectively.

Description

technical field [0001] The invention relates to two kinds of tumor-targeting photosensitizers and their preparation methods and applications. Background technique [0002] In recent years, the morbidity and mortality of cancer are on the rise, seriously threatening human health. So far, there is no effective method to curb the occurrence and development of cancer, and it is particularly urgent to find new and effective cancer diagnosis and treatment methods. Photodynamic therapy (PDT) is a new treatment for malignant tumors that has emerged in the past two decades. Compared with traditional treatment methods such as surgery, radiotherapy and chemotherapy, its significant advantage is that it can selectively give target The tissue is illuminated, because the photosensitizer is only effective in the light range, thereby reducing the damage to normal tissues, so as to achieve the purpose of physical targeted therapy. The three elements of photodynamic therapy are photosensiti...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K49/00A61K47/48A61P35/00A61P15/14
Inventor 舒春英甄明明王春儒
Owner 赤峰福纳康生物技术有限公司
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