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Structure and preparation method of a liver-targeted platinum-loaded nano-prodrug

A platinum nano- and liver-targeted technology, applied in the field of biomedicine, can solve the problems of high toxicity of cancer cells, discounted chemotherapy effects, and strong side effects of patients, and achieve enhanced killing ability, prevention of non-specific adsorption, and good blood stability Effect

Active Publication Date: 2019-09-10
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] Studies have shown that Pt(II) is highly toxic to cancer cells, and when used as chemotherapy drugs, the side effects of patients are relatively strong, which greatly reduces the effect of chemotherapy

Method used

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  • Structure and preparation method of a liver-targeted platinum-loaded nano-prodrug
  • Structure and preparation method of a liver-targeted platinum-loaded nano-prodrug
  • Structure and preparation method of a liver-targeted platinum-loaded nano-prodrug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Preparation of liver-targeted platinum-loaded nanoprodrugs for liver cancer treatment:

[0032] 1) Tetrabutylammonium alginate (ALG-TBA) preparation: HCl aqueous solution (0.6M, 30mL) was added to ethanol (30mL), ALG-Na (2.0g) was added to the mixed solution, stirred overnight at 4°C ; ALG-H was obtained by suction filtration, washed with ethanol and acetone in turn, and dried overnight at 40°C in vacuum; the dried alginic acid was dispersed in 100mL distilled water, and tetrabutylammonium base (TBAOH) was added dropwise under stirring conditions. When the polymer is completely dissolved, the pH is adjusted to 7.0-10.0, dialyzed, and freeze-dried to obtain white ALG-TBA.

[0033] 2) Cisplatin prodrug dichloro bis (hydroxide) diammine platinum (IV) (cis, trans, cis-[PtCl 2 (OH) 2 (NH3) 2 ]) Preparation method: dry cisplatin cis-[PtCl2(NH3)2] (0.20g, 6.6*10 -4 mol) was dispersed in 5ml of water, and a 10-fold excess of H2O2 (30% w / v, 7.0mL, 6.6*10 -3 mol),...

Embodiment 2

[0041] Example 2: Concentrated stability study of liver-targeted platinum-loaded nano-prodrugs for liver cancer treatment:

[0042] Preparation of liver-targeted platinum-loaded nano-prodrug concentrate: ALG@GA, Pt(IV) obtained in step 7 of Example 1 by centrifugation (GA:Pt(IV):ALG-TBA=1:2 :4) Nanoparticles were centrifuged at 25,000 rpm for 1 hour. After discarding the supernatant, a platinum-loaded drug nanoparticle concentrate with mouse experiment capability was obtained, wherein the concentration of platinum was 140ug. / ml. Ultrasonic disperse and shake the concentrate, the particle size is 160nm, characterized by DLS, see appendix Figure 4 . It is proved that the nanoparticles have good concentration stability.

Embodiment 3

[0043] Example 3: Determination of the release curve of the liver-targeted platinum-loaded nano-prodrug for the treatment of liver cancer:

[0044] Take 1ml of the liver-targeting platinum-loaded nano-prodrug solution and add it to 70ml of PBS buffer solution containing 0mM glutathione (GSH) and 10mM GSH, then take out 2ml of the solution at a fixed time point, and measure its concentration by ICP to obtain the drug in For the release curves under different reducing environments, see the appendix Figure 5 . In the presence of reducing substances, the release of drugs was significantly increased and there was a sustained release effect.

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Abstract

The invention discloses a liver-targeted platinum-loaded nanometer prodrug for treating liver cancers and a preparation method thereof. The liver-targeted platinum-loaded nanometer prodrug is prepared by taking sodium alginate with the good biocompatibility as a framework to be modified with glycyrrhetinic acid (GA) with a liver cancer cell targeting capacity and a tetravalent platinum compound (PtCl2(OH)2(NH3)2) through a self-assembly technique. In-vitro drug releasing and cytotoxicity tests prove that the platinum-loaded drug nanoparticles have the good blood stability and the intracellular slow-release effect and also have the tumor cell killing capacity. The nanometer prodrug is expected to be used for targeting treatment on the liver cancers and has a good application prospect in the biomedical field.

Description

[0001] Technical field: [0002] The invention relates to a liver-targeting platinum-loaded nanometer prodrug and a preparation method thereof. The nanoparticle prepared by the method is suitable for treating liver cancer and belongs to the technical field of biomedicine. [0003] Background technique: [0004] According to the "World Cancer Report" released by the World Health Organization (WHO) in 2014, among all kinds of malignant tumors in the world, the number of deaths from liver cancer ranks second in the world, and the incidence and death of liver cancer from my country It accounts for more than half of the world (OrganizationWH.World Cancer Report 2014.). In my country, liver cancer is the malignant tumor with the highest mortality rate. It has the characteristics of difficulty in early diagnosis, high degree of malignancy, strong invasiveness, and short survival period of patients. Chemotherapy is currently the main intervention for liver cancer besides surgery. Com...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/61A61K47/54A61K33/24A61P35/00A61P1/16
Inventor 袁直王蔚王新宇
Owner NANKAI UNIV
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