Drug-loaded nanoparticles for targeted immunotherapy of pancreatic cancer and its application

A nanoparticle and pancreatic cancer technology, applied in gene therapy, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of limited in vivo application and lack of effective carriers

Inactive Publication Date: 2018-03-16
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

RNA interference induced by siRNAs (small interference RNA) is a useful tool for specifically silencing target genes, but the lack of effective carriers limits its in vivo application

Method used

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  • Drug-loaded nanoparticles for targeted immunotherapy of pancreatic cancer and its application
  • Drug-loaded nanoparticles for targeted immunotherapy of pancreatic cancer and its application
  • Drug-loaded nanoparticles for targeted immunotherapy of pancreatic cancer and its application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] The targeting carrier of this example includes CD44v6 single chain antibody, and nanocarrier IONP-PEI, which carries siBmi-1. The content of this embodiment includes two parts: experimental method and conclusion analysis.

[0023] 1. Experimental method

[0024] 1. Cell culture

[0025] Human pancreatic cancer cell line Panc-1 was cultured in high-glucose DMEM medium containing 10% fetal bovine serum at a constant temperature of 37°C and 5% CO 2 cultured in an incubator.

[0026] 2. Targeting carrier construction

[0027] scFvCD44v6 (CD44v6 single-chain antibody) was synthesized according to the methods disclosed in Chinese patents 2011102402903 and 2011102402871. ScFvCD44v6 is coupled to PEI at a mass ratio of 1:1, and the process is briefly described as follows:

[0028] ① Prepare the IONP-PEI complex according to the ratio, dissolve mal-PEG-NHS in sterilized deionized water, add scFv to the complex at a molar ratio of 1:10, mix well, and incubate at room tempera...

Embodiment 2

[0176] The targeting carrier of this example includes CD44v6 single-chain antibody and nanocarrier IONP-PEI, which co-load gemcitabine and siBmi-1. The content of this embodiment includes two parts: experimental method and conclusion analysis.

[0177] 1. Experimental method

[0178] 1. Cell culture

[0179] Human pancreatic cancer cell line Panc-1 was cultured in high-glucose DMEM medium containing 10% fetal bovine serum at a constant temperature of 37°C and 5% CO 2 cultured in an incubator.

[0180] 2. Preparation and characterization of Gem-IONP (carrier IONP carrying gemcitabine) and svFv-Gem-IONP (targeting carrier carrying gemcitabine and siBmi-1)

[0181] (1) In an ice bath, add triethylamine (Triethylamine) and acid-sensitive tetrapeptide (9–fluoronylmethoxycarbonyl(Fmoc)-Gly-Phe-Leu-Gly(GFLG)-nitrophenyl ester peptide) according to 7.5umol: 6.8μmol To 1.0mol acetonitrile solution.

[0182] (2) Gemcitabine and triethylamine (Triethylamine) were dissolved in 1 ml o...

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Abstract

The present invention provides a targeting carrier for treating pancreatic cancer, which includes: CD44v6 single-chain antibody for targeted recognition of pancreatic cancer cells, and nanocarrier IONP-PEI; wherein CD44v6 single-chain antibody and nanocarrier IONP-PEI PEI-coupled. In another aspect, the present invention provides a nanoparticle for treating pancreatic cancer, which includes the aforementioned targeting carrier, silencing RNA, and gemcitabine chemotherapeutic drug, wherein the silencing RNA and gemcitabine are complexed on the aforementioned targeting carrier. The invention constructs a non-viral gene carrier with high efficiency, safety and targeting function. Coupling silencing RNA and gemcitabine through nanocarriers and anti-CD44v6 single-chain antibody, combining gene therapy, chemotherapy and biological targeted therapy, provides new ideas and scientific basis for the development of new anti-pancreatic cancer drugs.

Description

technical field [0001] The present invention relates to targeting vectors, nanoparticles and applications thereof for the treatment of pancreatic cancer Background technique [0002] Pancreatic cancer is one of the common malignant tumors of the digestive tract, which has the characteristics of insidious onset, easy metastasis, and low long-term survival rate. Radical surgical resection is the first choice for the treatment of pancreatic cancer, but most pancreatic cancer patients are diagnosed at an advanced stage, and the surgical resection rate is <20%. Chemotherapy is the main treatment, but due to the existence of tumor chemotherapy drug resistance, chemotherapy drugs are not effective It is very ideal, and it is an urgent clinical problem to develop new drugs to treat pancreatic cancer more effectively. Since 1997, gemcitabine has been the first-line drug for clinical anti-pancreatic cancer treatment, but no breakthrough has been made in terms of long-term efficacy...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/68A61K48/00A61K9/14A61P35/00A61P1/18A61K31/7068
Inventor 陈茵婷黄开红曾林涓李佳佳
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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