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Targeted liposome drug delivery system used for tumor imaging, preparation method and application

A technology targeting liposome and drug delivery system, which is applied in the field of liposome drug delivery system and preparation of near-infrared fluorescent dyes, which can solve the problems of inconspicuous development, low signal intensity, and no expression, etc. Fluorescence signal intensity, high signal intensity, effect of increased distribution

Inactive Publication Date: 2013-10-09
SHANGHAI NAT ENG RES CENT FORNANOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, current tumor imaging reagents still have shortcomings such as low signal intensity and inconspicuous imaging.
[0004] Studies have shown that Neuropilin-1 (NRP-1) is a specific receptor expressed on the surface of some tumor cells and vascular endothelial cells, and has been found in many types of tumors, including prostate cancer, breast cancer, melanoma, pancreatic cancer and Glioma, but not expressed in corresponding normal tissue epithelial cells
There is no report on the use of NRP-1 receptor or RPAKPAR polypeptide-mediated nano drug delivery system for tumor imaging

Method used

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  • Targeted liposome drug delivery system used for tumor imaging, preparation method and application
  • Targeted liposome drug delivery system used for tumor imaging, preparation method and application

Examples

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Effect test

Embodiment 1

[0018] Example 1: Preparation and Characterization of RPAKPAR-Liposome / DiR.

[0019] The composition of the liposome membrane material formulation is HSPC (hydrogenated soybean phospholipid) / Chol (cholesterol) / mPEG-DSPE (polyethylene glycol-distearoylphosphatidylethanolamine complex) (50: 50: 2, mol / mol) , The PEG liposome membrane material modified by RPAKPAR is formulated as HSPC / Chol / mPEG-DSPE / RPAKPAR-PEG-DSPE (50: 50: 2: 0.5, mol / mol). Dissolve the above components in chloroform, add 30 μl of DiR methanol solution (1.5 mg / ml), remove the solvent by rotary evaporation, add physiological saline to the lipid film, ultrasonically disperse and rotate and oscillate in a water bath at 60 ° C to obtain DiR lipid body suspension. Thereafter, after heating to 60°C, a 50nm carbonate membrane can be directly extruded through the membrane to obtain liposomes of desired size. The particle size of the liposome was measured by dynamic light scattering method, and the result showed that ...

Embodiment 2

[0020] Example 2: Preparation and Characterization of RPAKPAR-Liposome / DiR.

[0021] The composition of the liposome membrane material formulation is HSPC (hydrogenated soybean phospholipid) / Chol (cholesterol) / mPEG-DSPE (polyethylene glycol-distearoylphosphatidylethanolamine complex) (55: 45: 2, mol / mol) , The PEG liposome membrane material modified by RPAKPAR is formulated as HSPC / Chol / mPEG-DSPE / RPAKPAR-PEG-DSPE (55: 45: 2: 0.5, mol / mol). Dissolve the above components in chloroform, add 30 μl of DiR methanol solution (1.5 mg / ml), remove the solvent by rotary evaporation, add physiological saline to the lipid film, ultrasonically disperse and rotate and oscillate in a water bath at 60 ° C to obtain DiR lipid body suspension. Thereafter, after heating to 60°C, a 50nm carbonate membrane can be directly extruded through the membrane to obtain liposomes of desired size. The particle size of the liposome was measured by dynamic light scattering method, and the result showed that ...

Embodiment 3

[0022] Example 3: Preparation and Characterization of RPAKPAR-Liposome / DiR.

[0023] The composition of the liposome membrane material formulation is HSPC (hydrogenated soybean phospholipid) / Chol (cholesterol) / mPEG-DSPE (polyethylene glycol-distearoylphosphatidylethanolamine complex) (55: 45: 2, mol / mol) , The PEG liposome membrane material modified by RPAKPAR is formulated as HSPC / Chol / mPEG-DSPE / RPAKPAR-PEG-DSPE (55: 45: 2: 0.5, mol / mol). Dissolve the above components in chloroform, add 10 μl of DiR methanol solution (1.5 mg / ml), remove the solvent by rotary evaporation, add physiological saline to the lipid film, ultrasonically disperse and rotate and oscillate in a water bath at 60 ° C to obtain DiR lipid body suspension. Thereafter, after heating to 60°C, a 50nm carbonate membrane can be directly extruded through the membrane to obtain liposomes of desired size. The particle size of the liposome was measured by dynamic light scattering method, and the result showed that ...

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Abstract

The invention belongs to a field of medicinal preparations, and relates to a liposome drug delivery system used for tumor imaging, wherein the system is modified by a polypeptide with an amino acid sequence of RPAKPAR and wraps a near-infrared fluorescent dye. According to the invention, the RPAKPAR polypeptide is a targeting head group and modified on surface of stealth liposome, and wraps the near-infrared fluorescent dye. After intravenous administration, through mediation effect of the RPAKPAR polypeptide, the carrier stealth liposome actively sends the near-infrared fluorescent dye to tumor positions, and penetrates tumor vasculatures into whole tumor tissues, thereby increasing distribution of the dye in the tumor positions; and then by using an in-vivo optical molecular imaging technology, the tumor imaging with relatively high fluorescent signal intensity can be provided.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a liposome drug delivery system and a preparation method and application of a near-infrared fluorescent dye-wrapped liposome modified by a polypeptide whose amino acid sequence is RPAKPAR. It is applied to tumor imaging and can enhance the intensity of fluorescent signals. Background technique [0002] The incidence of malignant tumors in my country is increasing year by year, seriously endangering the health of the people. Many cancers are secretive in onset and have no obvious clinical symptoms in the early stage. At the same time, there is still a lack of specific medical means for real-time monitoring of tumor occurrence, development, and metastasis. Molecular imaging, which was born in the United States in the late 1990s, is a non-invasive real-time imaging of life or internal physiological and pathological processes at the molecular and cellular levels. It can diagn...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K9/127
Inventor 闫志强杨一祎钟建魏岱旭何丹农
Owner SHANGHAI NAT ENG RES CENT FORNANOTECH
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