PEDF gene composite targeted by tumor cell folate receptor

A folic acid and gene technology, applied in the field of medicine, can solve the problems of low cell uptake efficiency, lack of selectivity of tumor cells, immunogenic infectivity and poor targeting

Inactive Publication Date: 2017-06-13
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Retroviruses, adenoviruses, and lentiviruses have technical shortcomings such as immunogenicity, potential infectivity, and poor targeting
Plasmids are simple, safe, and cheap, and can carry large doses of DNA. However, due to the degradation of naked DNA by nucleases in vivo, the gene expression time is very short and cannot be used clinically; cationic liposomes are currently the The widely used gene transfection carrier has the advantage of high gene transfer efficiency; chitosan is also a gene transfection carrier with potential application value, but the currently reported carrier carrying PEDF gene is chitosan microspheres, Technical defects of large particle size and low cell uptake efficiency
[0004] In the previous authorized invention patent 201010136539.1 of our research group, the technology of delivering PEDF gene with PLGA nanoparticles was disclosed, which can realize the efficient delivery of PEDF gene in vivo; Set and gene expression levels need to be further improved

Method used

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  • PEDF gene composite targeted by tumor cell folate receptor
  • PEDF gene composite targeted by tumor cell folate receptor
  • PEDF gene composite targeted by tumor cell folate receptor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1～5

[0019] Embodiment 1~5 does not add the preparation of the folic acid modified lipid of spacer

[0020] The specific feeding is as follows:

[0021]

[0022]

[0023] The specific operation is: dissolve folic acid (0.42mmol), NHS (0.5mmol), EDCI (0.5mmol) and triethylamine (4mmol) in 5ml of anhydrous dimethyl sulfoxide, and add dropwise to phospholipids containing amino groups or derivatives thereof. (DSPE, SA, 0.5mmol) in DMSO. After reacting at 25°C to 30°C for about 120h to 144h, transfer the reaction solution into a dialysis bag (MWCO=1000Da), and dialyze with 20% (v / v) DMSO and water as the dialysis medium respectively. After dialysis for 14 days, transfer the dialysis sample to Put it in a silk bottle and lyophilize to obtain folic acid-cholesterol or folic acid-phospholipid (ie folic acid-modified lipid). Folic acid reaction, purification and lyophilization were protected from light during the whole process, and the product was stored in a desiccator protected fr...

Embodiment 6～10

[0024] Examples 6-10 Preparation of folic acid-modified lipids using α-carboxy-ω-amino polyethylene glycol as a spacer

[0025] The specific feeding is as follows:

[0026] Example number 6 7 8 9 10 α-Carboxyl-ω-amino polyethylene glycol molecular weight (Daltons) － 200 1000 3500 5000 Aminocaproic acid + － － - - cholesterol + + － - - Hydroxy-modified DC-cholesterol － － + － - PG － － － + － DCP － － － － +

[0027] The specific operation is: take 0.5 mmol of α-carboxy-ω-amino polyethylene glycol (protected at the amino end) or aminocaproic acid (protected at the amino end), 0.75 mmol of lipid material (cholesterol or phospholipid), and 4-dimethylaminopyridine 0.75mmol and 0.75mmol of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide were dissolved in 100ml of dichloromethane, and the reaction was about 72-96h. The organic solvent was removed by rotary evaporation under reduced pressure, and the crude produ...

Embodiment 11～15

[0028] Examples 11-15 Preparation of folic acid-modified lipids using diaminopolyethylene glycol as a spacer

[0029] The specific feeding is as follows:

[0030] Example number 11 12 13 14 15 Diaminopolyethylene glycol molecular weight (Daltons) 400 2000 5000 1000 1500 cholesterol + － + － － Hydroxyl modified DOPC － + － + +

[0031]The specific operation is: dissolve lipid (cholesterol or phospholipid) (10mmol), succinic anhydride (50mmol), and DMAP (5mmol) in 50mL of dichloromethane, reflux vigorously at 45°C, and stir for 48h to obtain succinylated lipid (cholesterol or phospholipids). Take succinylated lipid (4mmol), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (10mmol), N-hydroxysuccinimide (10mmol) dissolved in a small amount Dichloromethane, dropwise added to 100ml of bisaminopolyethylene glycol (5mmol) dichloromethane solution, stirred at room temperature for about 72h ~ 96h. The reaction solution was mixed with 60-m...

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Abstract

The invention relates to the field of medicines, in particular to a PEDF gene composition targeted by a tumor cell folate receptor as well as a preparation method of the PEDF gene composition and a use of the PEDF gene composition. The invention constructs a folate modified PEDF gene composition which can selectively transmit coded PEDF plasmids to the tumor cell by the folate receptor highly expressed by a tumor part, so that the tumor cell is induced to die, multiplication, invasion and transfer of the tumor cell are inhibited, and therefore, the anti-tumor effect is brought into play, and a better anti-tumor effect is achieved.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a tumor cell folic acid receptor-targeted PEDF gene complex, a preparation method and application thereof. Background technique [0002] Pigment epithelium-derived factor (PEDF) is an endogenous 50kDa secreted glycoprotein distributed throughout the body. It was first discovered and reported as a factor in retinal endothelial cells in 1989. With the development of time, PEDF mRNA has been confirmed to exist widely in most fetal or adult normal tissue cells (such as plasma, heart, lung, ovary) and tumors. PEDF has direct tumor suppressor properties, mainly through anti-tumor apoptosis, anti-tumor differentiation and anti-tumor proliferation; it also has indirect tumor suppressor properties, mainly through vascular endothelial growth factor (VEGF) and induction of endothelial cell apoptosis anti-tumor angiogenesis. As an anticancer factor, PEDF has a good therapeutic effect in a series of...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K9/127A61K47/22A61P35/00
CPCA61K48/0025A61K9/127A61K47/22
Inventor 宋相容魏于全
Owner SICHUAN UNIV
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