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Photodynamically induced co-controllable delivery system and its construction method

A delivery system, the technology of CORM-401, is applied in the field of photodynamically induced CO controllable delivery system and its construction, which can solve the problems of difficult-to-reach lesions, lack of targeting of gas, systemic toxicity, etc. Good in vitro and in vivo anti-tumor effect, good biosafety, and high CO release effect

Active Publication Date: 2019-05-28
NANJING TECH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, there are available CO inhalation devices clinically, which can directly deliver a certain amount of CO to the body through the device, but these devices face many problems: 1) inhalation of a large amount of CO is likely to cause systemic toxicity; 2) direct inhalation of CO The gas lacks targeting and may cause great damage to living organisms
However, most photoCORMs use ultraviolet light to stimulate the release of CO. Ultraviolet light has weak penetration into tissues and is difficult to reach deep-seated lesion tissues. High-energy ultraviolet light will also produce phototoxic effects on tissues and cells.

Method used

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  • Photodynamically induced co-controllable delivery system and its construction method
  • Photodynamically induced co-controllable delivery system and its construction method
  • Photodynamically induced co-controllable delivery system and its construction method

Examples

Experimental program
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Effect test

Embodiment 1

[0046] Feasibility study of a method for photodynamically induced release of CO.

[0047] Different concentrations of photosensitizer Ce6 and carbon monoxide releasing molecule CORM-401 (the concentration of CORM-401 was fixed at 1 mM, and the concentration ratio of Ce6 to CORM-401 was from 0.01:1 to 1:1) were dissolved in phosphate buffer at pH 7.4 ( PBS 7.4), and placed together with the CO gas detector in a transparent cylindrical separable airtight container, closed system. Near-infrared light at 665nm (optical energy density of 11.5 mW / cm 2 ) under continuous irradiation, record the concentration of CO by reading the readings of the CO gas detector at different time points, and calculate the amount of CO released by each CORM-401 molecule.

[0048] Assuming that both the gas phase and the liquid phase in the container reach equilibrium, and the pressure in the container is 1 standard atmospheric pressure, the amount of CO released by CORM-401 (N CO [mol]) is calculated ...

Embodiment 2

[0055] Construction of nanogel delivery system based on photodynamically induced CO release method.

[0056] The conjugate G3-Ce6 was synthesized through the covalent coupling reaction between the three-generation lysine dendrimer G3-Lys with POSS as the core and lysine as the branch unit and the photosensitizer Ce6. Specifically, under nitrogen protection, Ce6 (83.53mg, 0.14mmol) was mixed with N,N'-dicyclohexylcarbodiimide (DCC) (433.29mg, 2.10mmol), N-hydroxysuccinimide (NHS) (241.69mg, 2.10mmol) was dissolved in 10mL of anhydrous N,N-dimethylformamide (DMF), and reacted overnight at room temperature to activate the carboxyl group. After removing dicyclohexylurea (DCU) by filtration, the obtained Carboxylated Ce6 (Ce6-NHS) was slowly added dropwise to the G3-Lys (1.00g, 0.07mmol) solution, and reacted in the dark for 24h, and then the obtained solution was dialyzed against DMF and water sequentially (the molecular weight cut-off of the dialysis bag was 1000Da) Finally, fre...

Embodiment 3

[0064] A CO gas detector was used to detect the CO release behavior of CORM@G3DSP-Ce6. Continuously irradiate the CORM@G3DSP-Ce6 solution with 665nm near-infrared to keep the optical energy density at 11.5mW / cm 2 , to detect the release of CO.

[0065] To explore the mechanism of photodynamically induced CO release, the H produced by G3DSP-Ce6 and CORM@G3DSP-Ce6 solutions under light induction was detected using Amplex Red reagent and horseradish peroxidase (HRP). 2 o 2 concentration changes. Dissolve G3DSP-Ce6 (Ce6 concentration 0.68 μM) and CORM@G3DSP-Ce6 (Ce6 concentration 0.68 μM, CORM-401 concentration 10 μM) in PBS 7.4, respectively, and take 50 μL of the solution into a 96-well plate, and use a 665 nm near After the infrared light continuously irradiates the solution (the whole process keeps the light energy density at 11.5mW / cm 2 ), add 50 μL of Amplex Red (100 μM) and HRP (0.2 U / mL) working solution to each well, and measure the fluorescence value of each well wit...

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Abstract

The invention discloses a photodynamic induced CO releasing method, a CO controlled delivery system and a building method thereof. The CO releasing method is characterized by carrying out controlled release of CO under irradiation of near-infrared light by mixing a photosensitizer responding to the near-infrared light and applied to photodynamic therapy with carbon monoxide releasing molecules CORM-401. The CO controlled delivery system built on the basis of the photodynamic induced CO releasing method comprises a photosensitizer responding to near-infrared light and applied to photodynamic therapy, carbon monoxide releasing molecules CORM-401 and a carrier loaded or integrated with the photosensitizer and the carbon monoxide releasing molecules CORM-401. According to the CO controlled delivery system, the photochemical effect generated by the photosensitizer under induction of the near-infrared light is capable of accelerating the CO controlled delivery system to enter cells for decomposing the nanogel under the action of glutathione in the cells and releasing CORM-401; the near-infrared light activates and simultaneously generates singlet oxygen and CO; the singlet oxygen and COare respectively applied to photodynamic therapy and CO gas therapy; the combined therapy is achieved; the anti-tumor effect is obviously improved.

Description

technical field [0001] The invention belongs to the technical field of medical biomaterials, and relates to a photodynamically induced CO release method, a photodynamically induced CO controllable delivery system and a construction method thereof. Background technique [0002] As a colorless and odorless gas, carbon monoxide (CO) has a strong binding ability to hemoglobin. After being inhaled into the human body, it will easily lead to the formation of carboxyhemoglobin in the blood, causing the hemoglobin to lose its ability to carry oxygen and lead to poisoning of the body. Therefore, CO has been used for a long time. Considered a type of "silent killer". In recent years, people have gradually realized that CO plays an important physiological and pathological role in organisms. It is followed by nitric oxide (NO) and hydrogen sulfide (H 2 S) After that, the third gasotransmitters (gasotransmitters) were discovered. CO has many important physiological functions and potent...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/28A61K47/59A61K47/69A61K47/34A61K33/00A61P35/00
CPCA61K33/00A61K41/0071A61K47/641A61K47/6903A61P35/00A61K2300/00
Inventor 蔡晓军吴立煌顾忠伟
Owner NANJING TECH UNIV
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