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Multifunctional nano probe for multimodal images and photothermal therapy of liver cancer and application of multifunctional nano probe

A nanoprobe, multifunctional technology, applied in the field of multimodal imaging, can solve the problems of increasing the sensitivity and specificity of imaging technology, increasing the number of patients, increasing the economic burden of patients, etc., to reduce fluorescence quenching and aqueous phase instability. The effect of reducing the radiation dose of X-ray and improving the spatial contrast of CT

Active Publication Date: 2014-04-16
FUZHOU HOSPITAL FOR INFECTIOUS DISEASE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, various auxiliary contrast enhancement agents have been widely used clinically to increase the sensitivity and specificity of the above-mentioned imaging techniques; for example: based on Gd 3+ The metal complex has been successfully used in nuclear magnetic imaging (MRI), but its injection may lead to increased tissue osmotic pressure, tissue edema and other toxic side effects
However, the sensitivity of most of the contrast agents currently used clinically needs to be further improved; low sensitivity will lead to high-dose injections, increasing toxic and side eff

Method used

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  • Multifunctional nano probe for multimodal images and photothermal therapy of liver cancer and application of multifunctional nano probe
  • Multifunctional nano probe for multimodal images and photothermal therapy of liver cancer and application of multifunctional nano probe
  • Multifunctional nano probe for multimodal images and photothermal therapy of liver cancer and application of multifunctional nano probe

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Embodiment 1

[0033] Suspend 1ml of chloroauric acid with a concentration of 1M in 49ml of Milli-Q ultrapure water (Millipore, USA), put the mixed 50ml of chloroauric acid suspension into a clean three-necked flask of 100ml system, and place in an oil bath And under the reflux device, heat to 150°C until just boiling, after boiling for 5 minutes, quickly add 6ml of trisodium citrate solution with a concentration of 0.015g / ml to it, with strong stirring, and continue heating for 20 minutes, then stop heating, Stir to room temperature to form a suspension of gold nanoparticles, the diameter of which is about 10-16 nm, and centrifuge at 12000 rpm for 15 minutes to collect the gold nanoparticles for later use.

Embodiment 2

[0035] Suspend the above precipitate in the newly prepared 10mM tris-HCl solution containing 2mg / ml dopamine (DA, Sigma company), adjust the pH to 8.5, and gently stir for about 6h, centrifuge at 7000-8000rpm for 15min and wash twice, The coated Au-PDA nanoparticles were collected and suspended in Milli-Q ultrapure water to obtain an Au-PDA suspension. At this time, the dopamine is oxidized and self-polymerized by light to form a PDA polydopamine layer, which is used to modify the surface of Au nanoparticles, and exposes a large number of amino groups on the surface of Au nanoparticles, which is easy to modify later.

Embodiment 3

[0037] Pipette 20 μl of DMSO solution containing 12.5 mg / ml ICG (indocyanine green, Tongren Chemical Research Institute (Shanghai)) and suspend in 400 μl of Milli-Q ultrapure water, then take 100 μl of the aforementioned solution and add it to Example 2. In the prepared 3ml Au-PDA suspension, adjust the pH to 6.5, shake at room temperature in the dark for 2 hours, rest for 2 hours, centrifuge at 7000-8000rpm for 10 minutes, wash twice to remove unadsorbed ICG molecules, and the obtained nanoparticles are suspended in Prepare 3ml of 0.02M Au-PDA-ICG nanosuspension in Milli-Q ultrapure water for later use. The above-mentioned Au-PDA-ICG nanosuspension already has the functions of CT imaging, near-infrared fluorescence imaging and photothermal conversion.

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Abstract

The invention provides an Au-ICG (gold-indocyanine green) lipidosome multifunctional nano probe and application thereof. The nano probe consists of a kernel and a shell, wherein the kernel is a nanogold particle of which the surface is wrapped with a poly-dopamine layer and adsorbs indocyanine green; the shell is a DSPE-PEG (distearoyl phosphatidyl ethanolamine-polyethylene glycol) lipidosome film which is coupled with lactobionic acid and is chelated with Gd<3+> ions. The Au-ICG lipidosome multifunctional nano probe disclosed by the invention can be used for various image modes such as MRI (nuclear magnetism imaging), CT (computed tomography) imaging and near infrared fluorescence imaging of the liver cancer; a patient only needs to stand medicine supplying of a contrast agent, and various diagnosis effects can be achieved; furthermore, by virtue of the improvement of the sensitivity, the using amount of the contrast agent can be reduced, so that the toxic and side effect is further relieved; under near infrared illumination at 808 nm, adsorbed ICG molecules can effectively convert light energy into heat energy to produce superhigh heat of 60-70 DEG C, so that liver cancer cells can be killed thermally; therefore, the multifunctional nano probe can be used as a multimodal contrast agent for liver cancer diagnosis and can be used as a photothermal therapy agent for the liver cancer.

Description

(1) Technical field [0001] The invention relates to a multimodal image for NMR, CT, and near-infrared imaging of liver cancer, and an Au-ICG liposome multifunctional nanoprobe for photothermal treatment and its application. (2) Background technology [0002] Hepatocellular carcinoma (HCC) is one of the most common malignant tumors clinically, and its incidence is increasing year by year. According to statistics, there are about 600,000 new patients with liver cancer every year in the world, and its fatality rate reaches the third place, only slightly behind lung cancer and gastric cancer. The number of new cases of hepatocellular carcinoma in my country accounts for about 55% of the world each year; the core of liver cancer prevention and treatment is early detection, early diagnosis and early treatment. Among them, early diagnosis is the most critical, that is, it can be diagnosed before the clinical symptoms of the patient or before the cancer infiltrates, so as to get ti...

Claims

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Application Information

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IPC IPC(8): A61K49/12A61K49/18A61K49/04A61K49/00A61K41/00A61K47/48A61K9/127A61P35/00
Inventor 刘景丰刘小龙黄爱民张达
Owner FUZHOU HOSPITAL FOR INFECTIOUS DISEASE
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