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Construction method of targeted nano particle transmission system for cancer diagnosis and treatment

A targeted nanoparticle and delivery system technology, applied in the field of MRI diagnosis and treatment and molecular targeting, can solve the problem of increasing the risk of renal systemic fibrosis, inability to accurately distinguish the boundary between tumor and normal tissue, and low sensitivity, etc. problem, achieve the effect of increasing bioavailability, reducing systemic side effects, and improving targeting

Active Publication Date: 2011-09-07
SOUTH CHINA UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Currently, gadolinium chelates are widely used clinically as MRI-enhanced contrast agents. However, this type of contrast agent is not sensitive to the diagnosis of early tumors and micrometastases, cannot accurately distinguish the boundary between tumors and normal tissues, and will increase the intensity of the renal system. Therefore, it is of great significance to develop new MRI-enhanced contrast agents to improve the diagnostic accuracy of MRI for early-stage cancer and its micrometastasis

Method used

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  • Construction method of targeted nano particle transmission system for cancer diagnosis and treatment
  • Construction method of targeted nano particle transmission system for cancer diagnosis and treatment
  • Construction method of targeted nano particle transmission system for cancer diagnosis and treatment

Examples

Experimental program
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Embodiment 1

[0031] (1) Preparation of single-chain antibody by cleavage of double-chain antibody: 20 μL of monoclonal antibody (abbreviation: Ab) of intercellular adhesion molecule-1 (abbreviation: ICAM-1) ICAM-1 , 0.5mg / ml, molecular weight: 95kDa) was added to 10μL 0.5mol / L EDTA solution; 60mg mercaptoethylamine was dissolved in 0.5mL PBS buffer containing 10μL 0.5mol / L EDTA, and pre-cooled and incubated at 4°C 15min; add mercaptoethylamine solution to Ab ICAM-1 The solution was incubated at 37° C. for 1.5 h; excess mercaptoethylamine was removed with a desalting column (model: PD-10 Desalting Columns, GE Healthcare, MWCO=5000 Da).

[0032] (2) Preparation of α-aminopolyethylene glycol-modified single-chain antibody: the poly(ethylene glycol) containing α-amino-ω-maleimide polyethylene glycol (abbreviation: mal-PEG-NH 2 ) and 10 μL of 0.5mol / L EDTA PBS buffer solution were pre-cooled in the refrigerator for 15 minutes to 4°C, and the single-chain antibody obtained in step (1) was added...

Embodiment 2

[0037] (1) Preparation of single-chain antibody by cleavage of double-chain antibody: 50 μL of monoclonal antibody (abbreviation: Ab) of prostate cancer stem cell antigen (abbreviation: PSCA) PSCA , 0.2mg / ml, molecular weight: 29kDa) was added to 10μL 0.5mol / L EDTA solution; 60mg mercaptoethylamine was dissolved in 0.5mL PBS buffer containing 10μL 0.5mol / L EDTA, and pre-cooled and incubated at 4°C 15min; add mercaptoethylamine solution to Ab PSCA The solution was incubated at 37° C. for 1.5 h; excess mercaptoethylamine was removed with a desalting column (model: PD-10 Desalting Columns, GE Healthcare, MWCO=5000 Da).

[0038] (2) Preparation of α-aminopolyethylene glycol-modified single-chain antibody: the poly(ethylene glycol) containing α-amino-ω-maleimide polyethylene glycol (abbreviation: mal-PEG-NH 2 ) and 10 μL of 0.5mol / L EDTA PBS buffer solution were pre-cooled in the refrigerator for 15 minutes to 4°C, and the single-chain antibody obtained in step (1) was added to it...

Embodiment 3

[0044] (1) Preparation of single-chain antibody by cleavage of double-chain antibody: 10 μL of monoclonal antibody (abbreviation: Avastin) of bevacizumab (abbreviation: Avastin) Avastin , 1mg / ml, molecular weight: 149kDa) was added to 10μL 0.5mol / L EDTA solution; 60mg mercaptoethylamine was dissolved in 0.5mL PBS buffer containing 10μL 0.5mol / L EDTA, and pre-cooled and incubated at 4°C for 15min ; Add mercaptoethylamine solution to Ab Avastin The solution was incubated at 37° C. for 1.5 h; excess mercaptoethylamine was removed with a desalting column (model: PD-10 Desalting Columns, GE Healthcare, MWCO=5000 Da).

[0045] (2) Preparation of α-aminopolyethylene glycol-modified single-chain antibody: the poly(ethylene glycol) containing α-amino-ω-maleimide polyethylene glycol (abbreviation: mal-PEG-NH 2 ) and 10 μL of 0.5mol / L EDTA PBS buffer solution were pre-cooled in the refrigerator for 15 minutes to 4°C, and the single-chain antibody obtained in step (1) was added to it and...

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Abstract

The invention discloses a construction method of a targeted nano particle transmission system for cancer diagnosis and treatment. The nano particle transmission system loaded with superparamagnetic ferroferric oxide and antineoplastic medicaments is constructed by being mediated by a single chain antibody. The antineoplastic medicaments are delivered to target sites in the whole body in a targeted medicament administration mode so as to treat cancers; target spots are identified by antibody-antigen high specificity combination effects; the antineoplastic medicaments can be transferred in vivoand have active targeting performance; and medicinal effects can be improved, and the toxic or side effects of the antineoplastic medicaments on normal tissues can be reduced. Meanwhile, the system can also be used as a nuclear magnetic resonance imaging technology contrast agent so as to improve the accuracy of monitoring the tumor variation conditions at the target sites in real time.

Description

technical field [0001] The invention belongs to the fields of antitumor drug delivery, cancer nuclear magnetic resonance imaging (MRI for short) diagnosis and treatment and molecular targeting. The invention relates to a construction method of a targeted nanoparticle delivery system for cancer diagnosis and treatment, in particular to a construction method of a single-chain antibody-targeted nanoparticle delivery system loaded with superparamagnetic ferric oxide and antitumor drugs. Background technique [0002] Nanoparticle pharmaceutical preparations have the advantages of improving the solubility of insoluble drugs, prolonging drug action time, improving bioavailability, changing and improving drug kinetic properties, etc., and have become one of the important research directions in the field of medicine in recent years. Under normal circumstances, nanoparticles without surface modification enter the blood circulation, and most of them are phagocytized by macrophages in t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/16A61K47/42A61K31/337A61P35/00
Inventor 魏坤凌友
Owner SOUTH CHINA UNIV OF TECH
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