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Composite nano material based on ferrocene and hypericin, preparation method and application

A composite nanomaterial, hypericin technology, applied in the field of photodynamic therapy materials, can solve the problems of the antioxidant system and immune microenvironment, and achieve rapid renal clearance, good anti-tumor effect, and high local concentration

Active Publication Date: 2022-05-06
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] At present, the treatment of solid tumors still faces great challenges, and the antioxidant system and immune microenvironment in the tumor microenvironment are the main problems

Method used

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  • Composite nano material based on ferrocene and hypericin, preparation method and application
  • Composite nano material based on ferrocene and hypericin, preparation method and application
  • Composite nano material based on ferrocene and hypericin, preparation method and application

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1. Preparation of nanomaterials

[0040] (1) polyethylene glycol polylysine (PEG 100 / PLL 40 ) (100 mg, 1 eq) was diluted in 200 μL dimethyl sulfoxide, and 10 mL tetrahydrofuran was slowly added to form a micellar solution.

[0041](2) Add Fc-NHS (N-succinimide ferrocenecarboxylate, 80mg, 15eq) to the micellar solution in step (1), and -NH on the PLL in PEG / PLL 2 residue reaction. The reaction was incubated overnight at room temperature to prepare a PEG / PLL / Fc solution.

[0042] (3) 200 μL of DMSO solution containing 10 mg of hypericin was dropped into the PEG / PLL / Fc solution to prepare a PEG / PLL / Fc / Hyp solution.

[0043] (4) Purify the two solutions of PEG / PLL / Fc and PEG / PLL / Fc / Hyp by dialysis for 48 hours.

[0044] 2. Performance analysis of nanomaterials

[0045] (1) The average particle size and particle size distribution of the PEG / PLL / Fc / Hyp nanoparticles prepared above were measured by a dynamic light scattering particle size analyzer (DLS). Take 2μM (1mL)...

Embodiment 2

[0055] Nanomaterials were prepared according to the reaction conditions in Table 1, and the process flow was referred to in Example 1. The particle size of the nanomaterials prepared in Table 1 was shown.

[0056] Table 1

[0057]

[0058] It can be seen from Table 1 that when the mass ratio of polyethylene glycol polylysine, hypericin and ferrocene is 10:1:8, the particle size of the obtained nanomaterials is the best. When the concentration of hypericin or ferrocene increases, the particle size distribution of nanomaterials increases continuously, and too large nanoparticles cannot be enriched near the tumor tissue through the EPR effect, and are easily trapped by the reticuloendothelial system. Decrease the effect of magnetic resonance imaging and photodynamic therapy.

Embodiment 3

[0060] According to mPEG / nPLL in Table 2, the particle size of PEG / PLL obtained in Example 1 is shown in Table 2 for the process flow.

[0061] Table 2

[0062] m / PEG n / PLL Average particle size / nm 10 10 -- 50 10 10 100 40 110 500 40 -- 100 100 910

[0063] "--" indicates that the particle size is too large to be measured.

[0064] It can be seen from Table 2 that if the proportion of PEG is too high, no particles will form, and if the proportion of PLL is high, the particle size will be large.

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Abstract

The invention discloses a composite nano material based on ferrocene and hypericin as well as a preparation method and application of the composite nano material. The preparation method comprises the following steps: adding polyethylene glycol polylysine, ferrocenecarboxylic acid N-succinimide ester and hypericin into a tetrahydrofuran medium, and self-assembling the product to form the composite nano material based on ferrocene and hypericin. The prepared composite nano material based on ferrocene and hypericin has the advantages of being high in local concentration, good in anti-tumor curative effect, rapid in kidney clearance, high in biocompatibility, small in toxic and side effects and the like. The good anti-tumor curative effect is reflected in that a large amount of active oxygen is generated, glutathione on the local part of a tumor is depleted, ferroptosis and hypericin-mediated photodynamic therapy generate a synergistic effect, meanwhile, immunogenic cell death is triggered, and the powerful anti-tumor effect is achieved.

Description

technical field [0001] The invention relates to the field of photodynamic therapy materials mediated by ferrocene and hypericin, in particular to a composite nanomaterial based on ferrocene and hypericin, a preparation method and an application. Background technique [0002] At present, the treatment of solid tumors still faces huge challenges, and the antioxidant system and immune microenvironment in the tumor microenvironment are the main problems. The antioxidant system in tumors can up-regulate corresponding antioxidants, especially glutathione (GSH) and glutathione peroxidase (GPX4), reduce the generation of lipid peroxides (LPO), and prevent lipid Peroxides damage cell membranes, thereby promoting tumor growth. Therefore, glutathione depletion can lead to the accumulation of reactive oxygen species in tumor cells, which is one of the methods to improve the effect of anti-tumor therapy. [0003] Ferroptosis is an iron-dependent programmed cell death proposed by the St...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K41/00A61K47/60A61K47/34A61K31/555A61P35/00B82Y5/00B82Y30/00B82Y40/00
CPCA61K41/0057A61K31/555A61K47/60A61K9/5146A61P35/00B82Y5/00B82Y30/00B82Y40/00A61K2300/00
Inventor 周晓璇韩玉鑫胡红杰胡秋慧
Owner ZHEJIANG UNIV
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