Magnetic resonance imaging nano-carrier, nano drug carrier system and preparation method thereof

A magnetic resonance imaging and nano-carrier technology, applied in the field of biomedicine, can solve the problems of lack of cell specificity and low uptake efficiency of target cells, and achieve the effects of overcoming poor selectivity, good biocompatibility, and low drug concentration

Active Publication Date: 2018-08-17
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

By improving the shortcomings of low uptake efficiency of CPPs target cells and lack of cell specificity, tumor-targeting CPPs were designed and synt

Method used

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  • Magnetic resonance imaging nano-carrier, nano drug carrier system and preparation method thereof
  • Magnetic resonance imaging nano-carrier, nano drug carrier system and preparation method thereof
  • Magnetic resonance imaging nano-carrier, nano drug carrier system and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1: Preparation and characterization of polymer nanoparticles F / A-PLGA@DOX / SPIO

[0083] (1) Under normal temperature and pressure (15-35°C, 1 standard atmospheric pressure), polylactic-co-glycolic acid (PLGA) (LA:GA=50:50, Mn=13000, Sigma, USA), ultra-small super-smooth Magnetic iron oxide nanoparticles (SPIO) (purchased from Sigma) and doxorubicin (DOX) were added to the acetone solution, and the mass concentration of polylactic-co-glycolic acid (PLGA) was configured to be 5 mg / mL, and the ultra-small superparamagnetic An acetone solution with a concentration of iron oxide nanoparticles (SPIO) of 1 mg / mL and a concentration of doxorubicin (DOX) of 500 μM.

[0084] (2) Add 3 mL of prepared acetone solution dropwise to 10 mL of Tween-80 aqueous solution (5 mg / mL), at a rate of 5 seconds between each drop, and stir overnight at 200 to 800 r / min to obtain Adriamycin PLGA aqueous solution with a concentration of 100 μM.

[0085] (3) Add 1-(3-dimethylaminopropyl)-3...

Embodiment 2

[0092] Example 2: In vitro anti-human lung cancer cell activity of polymer nanoparticles F / A-PLGA@DOX / SPIO

[0093] After A549 cells, HeLa cells, A375 cells and L02 cells were digested and resuspended according to conventional methods, the tumor cell density was 2×10 4 cells / mL, the normal cell density is 4×10 4 cells / mL, add to 96-well plate, 100μL per well. After culturing overnight, add 100 μL / well of medium containing different concentrations of drugs (0, 0.015625, 0.03125, 0.0625, 0.125, 0.25, 0.5) according to the experimental settings, add 30 μL MTT (5 mg / mL) to each well after 72 hours, and incubate After 3.5 hours, the supernatant was discarded, and then 150 μL of DMSO was added to dissolve formazan, which was detected by an enzyme-linked immunosorbent assay (570 nm). Calculate the half inhibitory concentration IC of the drug on the cells 50 And safety factor (Safety index, SI) ( Figure 7 and Table 1).

[0094] Table 1 The half inhibitory concentration IC of dif...

Embodiment 3

[0103] Example 3: In vivo localization and pharmacokinetic experiments of polymer nanoparticles F / A-PLGA@DOX / SPIO

[0104] Preparation of tumor-bearing nude mouse model: collect human non-small cell lung cancer cells A549 cultured in vitro, count them, and adjust the concentration of the cell suspension to 1×10 7 cells / ml, inoculate 0.1ml of cell suspension into 4-5 weeks old nude mice (BALB / c-nu nude mice, 2-4 weeks old, weighing about 18-22g, Beijing Huafukang Biotechnology Co., Ltd.) Subcutaneous at base of hind limbs.

[0105] Grouping and administration: measure the diameter of transplanted tumors in nude mice with a vernier caliper, and wait until the tumor grows to 75-100mm 3 Afterwards, the animals were randomly divided into three groups, with 3 animals in each group. Group A was given SPIO (5 mg / kg), group B was given F / A-PLGA@SPIO (5 mg / kg), and group C was given F / A-PLGA@DOX / SPIO (5 mg / kg). Drugs were administered through the tail vein. At the same time, nuclear...

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Abstract

The invention belongs to the field of bio-medicine, and discloses a magnetic resonance imaging nano-carrier, a nano drug carrier system and a preparation method thereof. According to the invention, two targeting molecules, namely folic acid and cell-penetrating peptide, are adopted, so that a targeting effect on tumors is improved, and meanwhile, anti-tumor activity in vitro and in vivo is enhanced. PLGA, which is low in toxicity and good in biocompatibility, is taken as the anti-tumor drug carrier, and the terminal of the PLGA is modified with CS, so that the functional nano-system is prepared. Meanwhile, nuclear magnetic imaging drugs and anti-tumor drugs are effectively loaded, so that the anti-tumor drugs can reach a tumor focus part in a specific mode, and tumor region nuclear magnetic localization of ferroferric oxide nanoparticles can be implemented; and meanwhile, a therapeutic effect with high selectivity and low toxicity can be achieved. With the application of the invention,shortcomings of conventional cytotoxic drugs which are poor in selectivity, relatively strong in toxic and side effects, capable of causing drug tolerance easily and the like can be overcome; and a utilization degree of the anti-tumor drugs can be improved and toxic and side effects can be reduced. The preparation method of the drug carrier system is simple and easy to implement; and the preparedproduct (the drug carrier system) is good in repeatability and stability.

Description

technical field [0001] The invention belongs to the field of biomedicine, in particular to a magnetic resonance imaging nano carrier, a nano drug loading system and a preparation method thereof. Background technique [0002] With rising morbidity and mortality, cancer is an important cause of death and a major public health problem worldwide. However, traditional chemotherapy drugs are non-selective, often highly toxic, and prone to multi-drug resistance of tumors. The new multifunctional nano drug delivery system is currently the most promising drug delivery, mainly because the nano system can effectively improve drug bioavailability, increase drug stability, prolong plasma circulation time, reduce drug side effects and overcome tumor Drug resistance and other characteristics, while diagnostic imaging and dynamic monitoring of response to drug therapy. [0003] The nano drug delivery system can passively target the tumor through high permeability effect and high retention...

Claims

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Application Information

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IPC IPC(8): A61K49/12A61K49/10A61K49/14A61K49/18B82Y5/00B82Y15/00A61K9/14A61K47/34A61K47/36A61K47/22A61K47/42A61K47/69A61K47/54A61K47/64A61K31/704A61P35/00
CPCA61K9/145A61K9/146A61K31/704A61K49/10A61K49/126A61K49/14A61K49/1833A61K49/1857A61K49/1863A61K49/1866A61K47/545A61K47/64A61K47/6937A61K47/6939A61P35/00B82Y5/00B82Y15/00
Inventor 陈填烽罗良平史长征高鹏陈樑
Owner JINAN UNIVERSITY
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