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Thermosensitive polymer-modified bivalent platinum nanocluster and preparation method and application thereof

A polymer, platinum nanotechnology, applied in the field of anti-tumor drug preparation, to optimize the synergistic anti-tumor effect of photothermal chemotherapy and ensure the effect of adjustable release

Active Publication Date: 2018-05-18
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The above results show that platinum-based materials have the potential of both chemotherapy and hyperthermia, but there is no report on the precise regulation of photothermal / chemotherapy anti-tumor effects by pure platinum nanomaterials

Method used

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  • Thermosensitive polymer-modified bivalent platinum nanocluster and preparation method and application thereof
  • Thermosensitive polymer-modified bivalent platinum nanocluster and preparation method and application thereof
  • Thermosensitive polymer-modified bivalent platinum nanocluster and preparation method and application thereof

Examples

Experimental program
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Embodiment 1

[0068] The preparation of embodiment 1 thermosensitive polymer PNA

[0069] In this example, the temperature-sensitive polymer ligand PNA is prepared by atom transfer radical polymerization: N-isopropylacrylamide (NIPAM) is used as the monomer of the temperature-sensitive polymer, and tert-butyl acrylate (tBA) is used as the polymer The monomeric precursor of the ligand, bis[2-(2′-bromoisobutyryloxy)ethyl] disulfide (BiBOEDS) as the initiator, tris(2-dimethylaminoethyl)amine ( Me 6 TREN) is the ligand, cuprous chloride (CuCl) is the catalyst, and the mixed solution of acetone and water four to one is the solvent for the ATRP reaction, NIPAM:tBA:BiBOEDS:Me6TREN:CuCl molar ratio=200:200:1:2 :2.

[0070] Specific steps are as follows:

[0071] 1) Put 2.26g of N-isopropylacrylamide (NIPAM) in the Schlenk reaction vessel tube, then add 8mL of acetone and 2mL of ultrapure water, stir at 1000rpm for 3min to completely dissolve NIPAM, then freeze in liquid nitrogen for 5min, and va...

Embodiment 2-5

[0075] Example 2-5 Preparation of bivalent platinum nanoclusters modified by thermosensitive polymers

[0076] This embodiment provides a bivalent platinum nanocluster modified by a temperature-sensitive polymer. The bivalent platinum nanocluster has a core-shell structure. sensitive polymer PNA.

[0077] The preparation method of the bivalent platinum nanocluster comprises the following steps:

[0078] 1) Weigh 0.5 g of the temperature-sensitive polymer ligand PNA obtained in Example 1, then add it to 10 mL of ultrapure water, stir at 1000 rpm for 3 hours to dissolve it, and adjust the pH to 8.0, according to the ratio in Table 1 below, mix the PNA solution with 1mL of 100mM hexachloroplatinic acid solution and finally adjust the volume to 15mL, adjust the pH to 8.0, put the above system in an oil bath at 30°C and stir at 600rpm Incubated for 12 hours to form nanogels. Transmission electron microscopy of nanogels formed with different feed ratios see Figure 4 A, 4B and 4...

experiment example 1

[0083] Take 500 μL each of the platinum nanoclusters obtained in Comparative Example 1 and Examples 2-4, then dilute to 15 mL with ultrapure water, and drop 5 μL onto a copper grid covered with a carbon film to dry naturally. Using a field emission transmission electron microscope (FTEM, Tecnai G2F30) to observe the morphology of each platinum nanocluster, lattice fringes, electron diffraction rings, and high-angle annular dark field for scanning-transmission electron microscopy (STEM) imaging to observe the outer layer of platinum nanoclusters Thermosensitive polymer ligand PNA and line scan for elemental analysis.

[0084] Figure 6 A shows that the platinum nanoclusters (comparative example 1) synthesized without PNA as a template are agglomerated in the form of chain beads, while Figure 6 B, 6C and 6D have three kinds of platinum nanoclusters (Example 2-4) synthesized with PNA as a template, which are spherical and well dispersed. Such as Figure 7 A, 7B, 7C and 7D sho...

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Abstract

The invention provides a thermosensitive polymer-modified bivalent platinum nanocluster and a preparation method and application thereof. The bivalent platinum nanocluster has a core-shell structure,the inner core comprises zero-valent platinum with divalent platinum on the surface and the shell is a temperature-sensitive polymer. The preparation method utilizes a thermosensitive polymer ligand as a template to synthesize bivalent platinum nanoclusters with different relative contents of divalent platinum and zero-valent platinum. Through adjustment and control of the relative content of divalent platinum and zero-valent platinum, the relative interaction intensity of the photothermal effect and the chemotherapy effect is precisely adjusted and controlled so that photothermal chemotherapy-combined anti-tumor effects are optimized.

Description

technical field [0001] The present invention relates to the field of preparation of antitumor drugs, more specifically, to a bivalent platinum nanocluster surface-modified by a temperature-sensitive polymer ligand capable of precisely regulating the antitumor effect of photothermal chemotherapy and its preparation method and its antitumor effect Applications. Background technique [0002] At present, cancer is still one of the major diseases threatening human life and health, and the incidence of cancer worldwide is on the rise. The treatment of cancer has always been a difficult point in research at home and abroad. The methods of clinical treatment of cancer include surgery, radiotherapy, hyperthermia and chemical drug treatment. Hyperthermia has attracted widespread attention because of its ability to significantly improve the antitumor effect of drugs. By heating the tumor tissue to 39-42°C, hyperthermia exerted multiple drug-sensitizing effects such as cell apoptosis,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/51A61K47/34A61K33/24A61P35/00
CPCA61K9/5146A61K33/24A61K41/0052A61K2300/00
Inventor 赵彦兵杨祥良赵浩彭晓乐徐家宝
Owner HUAZHONG UNIV OF SCI & TECH
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