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Targeted delivery system based on functionalized macrophages/monocytes, and construction and application of targeted delivery system

A delivery system and functionalized technology, applied in the field of biomedicine, can solve the problems of inability to specifically target specific tumor-specific targets, and inability to meet precise targeted therapy

Active Publication Date: 2020-10-02
陕西巨世康济生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing macrophage membrane biomimetic nanomaterial delivery only uses the functional protein of the cell itself to target the tumor, and cannot specifically target the specific target of a specific tumor. Clinical needs for targeted therapy

Method used

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  • Targeted delivery system based on functionalized macrophages/monocytes, and construction and application of targeted delivery system
  • Targeted delivery system based on functionalized macrophages/monocytes, and construction and application of targeted delivery system
  • Targeted delivery system based on functionalized macrophages/monocytes, and construction and application of targeted delivery system

Examples

Experimental program
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Effect test

Embodiment 1

[0059] Example 1 Construction and targeting verification of functional macrophages

[0060] (1) Synthesis of a transmembrane-expressed protein or polypeptide macromolecular nucleic acid sequence (synthesized by Shanghai Jierui Bioengineering Co., Ltd.), the full-length nucleic acid sequence (SEQ ID NO.7) consists of four parts, which are membrane localization signals Peptide sequence (SEQ ID NO.1, including promoter), protein or polypeptide molecular sequence (SEQ ID NO.2), linker sequence ① (SEQ ID NO.3), transmembrane sequence (SEQ ID NO.4), linker sequence ② (SEQ ID NO.5), GFP sequence (SEQ ID NO.6, including terminator), and the protein sequence (SEQ ID NO.14) corresponding to the nucleic acid sequence are: signal peptide sequence (SEQ ID NO.8) , protein or polypeptide macromolecular sequence (SEQ ID NO.9, Affibody as an example), linker sequence ① (SEQ ID NO.10), transmembrane sequence (SEQ ID NO.11), linker sequence ② (SEQ ID NO.12 ), GFP sequence (SEQ ID NO.13).

[00...

Embodiment 2

[0081] Example 2 Establishment of functionalized macrophage nano-drug delivery system and verification of tumor suppression (taking polylactic-co-glycolic acid (PLGA) as an example)

[0082] (1) Detection of functionalized macrophage membrane coated nanoparticles: PLGA nanoparticles were prepared by W / O double emulsion method, and the extracted cell membrane of mouse macrophage cell line RAW264.7 and PLGA nanoparticles were squeezed through nitrogen gas The extruder was repeatedly extruded 20 to 30 times, and DLS was performed on the nanoparticles and the nanoparticles wrapped by the RAW membrane of ordinary macrophages (M@NPs) and the nanoparticles wrapped by the Affibody-RAW membrane of functionalized macrophages (AM@NPs). The test results are shown in Table 1. The increase in particle size and the change in potential after wrapping the cell membrane proved that the cell membrane was successfully coated on the nanoparticles.

[0083] The preparation steps of nanoparticles a...

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Abstract

The invention provides a targeted delivery system based on functionalized macrophages / monocytes, and construction and application of the targeted delivery system. According to the invention, bioactiveprotein or polypeptide which can undergo transmembrane expression is adopted to modify macrophages / monocytes so as to realize functionalization of the macrophages / monocytes, a functionally modified cell membrane is used as a shell to coat nanoparticles so as to construct the targeted delivery system, so a bionic nanometer material slowly releases a drug at a tumor part and is endowed with a tumor-specific targeting function; and tumor-specific targeting and deep tumor delivery are realized by combining the sustained drug releasing function of the nanometer material with a functionalized macrophage membrane, and the tumor enrichment amount of the nanometer material and the tumor treatment effect of the drug-loaded nanometer material are further enhanced.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to a targeted delivery system based on functionalized macrophages / monocytes and its construction and application. Background technique [0002] Tumor promotes its own development through various mechanisms such as malignant proliferation, invasion and metastasis, and immune evasion, and creates a tumor microenvironment (TME) for itself to further resist the body's immunity and maintain development, making the three conventional treatment methods of surgery, radiotherapy and chemotherapy Effective treatments are still not available for many cancers. Targeted therapy is a rapidly developing tumor treatment method in recent years. In targeted tumor therapy, nano-drug delivery systems can effectively deliver drugs to target tissues, organs, and target cells, thereby regulating the pharmacokinetics, efficacy, side effects, and immunogenicity of drugs. However, there are ...

Claims

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Application Information

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IPC IPC(8): C12N5/10C12N15/867A61K47/62A61K47/51A61K47/69A61K31/704A61P35/00
CPCC12N5/0645C12N5/0639C12N15/86A61K47/62A61K47/51A61K47/6937A61K31/704A61P35/00C12N2510/00C12N2740/15043C12N2800/107
Inventor 宁蓬勃王忠良龚小程姚慧敏刘敏龚春梅夏玉琼张象涵贾茜
Owner 陕西巨世康济生物科技有限公司
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