Medicament carrier for targeted medicament delivery on diseases related to macrophage and preparation method thereof
A macrophage and disease-targeting technology, applied in the field of recombinant rotavirus Vp6 gene expression and in vitro assembly, to improve the therapeutic effect, achieve mass production, and avoid degradation
Inactive Publication Date: 2012-09-05
SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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[0006] For MAS and TAM, there is no specific targeted drug at present, and a safe and effective targeting carrier is urgently needed for the specific treatment of macrophages
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[0028] The Vp6 genes used in the present invention are all group A rotaviruses, which are respectively rotavirus Vp6 genes derived from monkeys, human Vp6 genes and pig Vp6 genes. These genes and encoded proteins are respectively shown in sequences 1, 2, and 3, each of which consists of 1356 nucleotides, encodes 397 amino acids, and has an open reading frame of 24-1217 nucleotides. Cloning these genes into prokaryotic expression vectors and expressing them in Escherichia coli BL21(DE3) to obtain proteins with a molecular weight of about 45KD, and then cross-linking the expressed proteins with drugs for in vitro assembly to obtain macrophage targeting Drug carrier.
[0029] The detailed preparation method of the drug carrier used for targeted drug delivery of macrophage-related diseases of the present invention is as follows:
[0030] 1. Plasmid construction
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Abstract
This invention discloses a medicament carrier for targeted medicament delivery on diseases related to macrophage and a preparation method thereof, the medicament carrier is hollow virus-like particles formed by prokaryotic expression and self-assembly of rotavirus coat protein Vp6 with specific identification ability to the macrophage; the internal surface or the external surface of the medicament carrier is chemically modified with medicament molecules. The preparation method comprises the following steps: firstly, extracting genes of structural protein Vp6 of A group rotavirus; secondly, cloning the genes of the structural protein Vp6 to a prokaryotic expression carrier; thirdly, performing expression in colibacillus BL21; and finally, crosslinking the expressed protein with the medicament and performing assembly to obtain the virus-like particles. By using the specific identification ability of the virus-like particles to the macrophage, medicaments are delivered to the macrophage to realize the functions of the targeted medicament delivery and slow release. The medicament carrier of the invention can effectively reduce the dosage and toxicity of the medicaments, prevent the medicaments from being degraded by internal environment, improve treating effect, and realize mass production and reduce manufacture cost at the same time.
Description
technical field [0001] The present invention relates to the expression and in vitro assembly of the recombinant rotavirus Vp6 gene, and in particular to the use of the assembly product for targeted drug delivery (targeted therapeutic drug delivery, targeted imaging and macrophage markers, etc.) for lymphocyte-related diseases . Background technique [0002] Virus like particles (VLP) are a kind of non-replication-competent, self-assembled proteins without genome. Under certain conditions, protein subunits can self-assemble into cage-like structures or virus-like nanoparticles of other shapes in an in vitro environment; they have regular structural forms, and different viruses have different sizes in the nanometer range (20nm- 200nm); the structure is orderly, and the monodispersity is good; the three-dimensional structure of many viruses has been analyzed at the atomic level; it can be produced in large quantities, and gram-level or even kilogram-level virus particles can ...
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IPC IPC(8): A61K47/48A61K47/42A61K45/00A61P37/00C12N15/70C12P21/02C12R1/19A61K47/64
Inventor 张智军赵庆欢黄洁
Owner SUZHOU INST OF NANO TECH & NANO BIONICS CHINESE ACEDEMY OF SCI
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