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Novel targeted lysosome ruthenium photocatalyst as well as preparation method and application thereof

A technology of photocatalysts and lysosomes, applied in the field of medicine, can solve problems such as the decline in the quality of life of patients and achieve high curative effect

Active Publication Date: 2021-03-12
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Radiation therapy and chemical drug therapy are clinically commonly used tumor treatment methods, but while achieving therapeutic effects, radiotherapy and chemotherapy often cause varying degrees of toxic and side effects, such as skin swelling and pain, listlessness, hair loss, and even bone marrow suppression, Side effects such as gastrointestinal reactions have greatly reduced the quality of life of many patients

Method used

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  • Novel targeted lysosome ruthenium photocatalyst as well as preparation method and application thereof
  • Novel targeted lysosome ruthenium photocatalyst as well as preparation method and application thereof
  • Novel targeted lysosome ruthenium photocatalyst as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] A novel targeting lysosome ruthenium photocatalyst, its structure is as formula (I):

[0033]

[0034] The preparation method of formula (I) compound:

[0035] Bis(2,2'-dipyridyl)ruthenium(II) dichloride dihydrate (0.0520g, 0.1mmol) and 4,4'-diphenyl-2,2'-bipyridine (0.0308g, 0.1 mmol) in ethanol (20 mL) was heated to 80° C., refluxed for 24 hours and then cooled to room temperature. The precipitate was filtered and washed with ethanol, and dried in vacuo to obtain an orange-red solid. The obtained crude product was purified by neutral alumina column chromatography (solvent: methanol / dichloromethane=1 / 99), and recrystallized by dichloromethane / diethyl ether to obtain orange-red crystalline ruthenium (II) complex (0.0619g, 0.078mmol), yield 78%. Characterized by mass spectrometry and NMR, its molecular formula is C 42 h 32 Cl 2 N 6 Ru, ESI-MS[CH3OH,m / z]:361[M-2Cl] 2+ . 1 H NMR (400MHz, DMSO) 9.37(d, J=1.6Hz, 2H), 8.91(d, J=8.1Hz, 4H), 8.20(d, J=1.7Hz, 4H), 8.0...

experiment example 1

[0039] The photostability of the formula (I) compound that embodiment obtains is tested

[0040] Put the luminescent quartz cuvette containing the PBS solution of the ruthenium complex (10M) under a 465nm light source for 5 minutes of radiation (the light dose is 11.7J / cm 2) to measure the absorbance of the solution. The effect of ruthenium(II) complexes under 465nm light radiation is as follows: figure 2 As shown, the ultraviolet-visible absorption spectrum of the ruthenium (II) complex does not change substantially before and after light irradiation, and it can be seen that the ruthenium (II) complex has strong photostability.

experiment example 2

[0042] Ability of Photocatalytic Oxidation of NADH by Ru(II) Complexes

[0043] Under photocatalysis, metal complexes can oxidize reduced coenzyme I (NADH) to its oxidized state (NAD + ), so the ruthenium complex (2M) and NADH (A 339nm =1.5) the luminescent quartz cuvette is placed under a 465nm light source for 5 minutes of radiation (the light dose is 11.7J / cm 2 ) to measure the absorbance of the solution. The effect of ruthenium(II) complexes on the oxidation of NADH under 465nm light irradiation is as follows: image 3 As shown, the ruthenium (II) complex has photocatalytic oxidation ability for NADH.

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Abstract

The invention relates to the field of medicine, in particular to a novel targeted lysosome ruthenium photocatalyst as well as a preparation method and application thereof. The novel targeted lysosomeruthenium photocatalyst has a high curative effect when applied to photodynamic therapy of liver cancer (HepG2 cells), can target lysosome in cells, has a photocatalytic oxidation effect on NADH and amino acid, is of great significance to research of efficient and low-toxicity ruthenium complex photosensitizers, and lays experimental and theoretical foundations for clinical development of novel metal antitumor drugs. The metal ruthenium (II) complex has no toxicity (IC50>100 [mu] M) to human liver cancer cell strains in the absence of illumination, but has very strong growth inhibition ability(IC50 = 0.51 [mu] M) to the human liver cancer cell strains under illumination, can target lysosome, and has photocatalytic oxidation ability to NADH in cancer cells.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a novel targeting lysosome ruthenium photocatalyst and its preparation method and application. Background technique [0002] With the aggravation of environmental pollution and population aging, cancer has become a major disease that threatens human health and is the second leading cause of death in the world. About 8.8 million people died of cancer in 2015, and an estimated 18.1 million new cancer cases and 9.6 million cancer deaths were estimated worldwide in 2018. According to the estimates of the World Health Organization, the number of new cancer cases in the world will reach 20 million in 2020, and at least 12 million people will die of cancer. The incidence of cancer in my country is increasing at a rate of 3% to 5% per year. [0003] Radiation therapy and chemical drug therapy are clinically commonly used tumor treatment methods, but while achieving therapeutic effects, radiother...

Claims

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Application Information

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IPC IPC(8): C07F15/00B01J31/18A61P35/00A61K41/00
CPCC07F15/0053B01J31/183A61P35/00A61K41/0057B01J2531/821B01J2531/0213B01J35/39
Inventor 黄怀义范中贤缪梦昭李文清
Owner SUN YAT SEN UNIV
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