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PSMA-targeted macrophage membrane-coated bionic nano-drug carrier and application thereof

A biomimetic nanotechnology, cell membrane technology, applied in application, drug combination, drug delivery, etc., can solve the problems of weak targeting and strong exogenous, and achieve the goal of improving stability, prolonging in vivo half-life, and improving targeted imaging capabilities. Effect

Pending Publication Date: 2022-04-12
AIR FORCE MEDICAL UNIV
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  • Abstract
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Problems solved by technology

[0009] The present invention organically combines bionic nanotechnology, genetic engineering technology and antibody technology to construct a biomimetic nanomedicine carrier wrapped in macrophage cell membrane targeting PSMA, which overcomes the defects of strong exogenous and weak targeting of traditional nanomedicine carriers. Provide a new strategy for the targeted diagnosis and treatment of prostate cancer, and provide a new idea for the development of nano-drugs

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  • PSMA-targeted macrophage membrane-coated bionic nano-drug carrier and application thereof

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Embodiment Construction

[0041] To achieve the specificity of biomimetic nanocarriers, the selection of target molecules is crucial. Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein, which is almost specifically expressed in all prostates. Cancer cells, and its expression level is closely related to the malignancy of prostate cancer, especially in advanced metastatic prostate cancer. Therefore, PSMA is considered an ideal target for prostate cancer diagnosis and therapy. At present, Antibody-drug conjugate (ADC) targeting PSMA has shown excellent prostate cancer targeting and anti-tumor activity in Phase I and Phase II clinical trials. Therefore, the use of PSMA antibodies to engineer macrophage membranes and biomimetic modification of nanocarriers has great application prospects.

[0042] The present invention selects the single-chain antibody gy-1 that specifically recognizes PSMA, and splices its light and heavy chain variable region genes with the CD8a hinge regio...

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Abstract

The invention discloses a PSMA-targeted macrophage membrane-wrapped bionic nano-drug carrier and application, a nanogold carrier is wrapped by a macrophage membrane, and a PSMA-targeted antibody based on a sequence as shown in SEQ.ID.NO.1 is expressed on the macrophage membrane in a transmembrane manner; the antibody is a gy-1 single-chain antibody, and is expressed on a macrophage cell membrane in a transmembrane manner through fusion expression with a CD8a hinge region and a CD8a transmembrane region. The preparation method comprises the following steps: constructing a lentiviral vector for expressing a transmembrane single-chain antibody by utilizing a genetic engineering method, packaging into lentivirus, infecting macrophages to express the transmembrane single-chain antibody, and extracting a cell membrane to carry out bionic modification on a nano-vector; the prepared nano-carrier is expected to overcome the two problems of strong exogenous property and weak targeting property of the traditional nano-drug carrier, and can be used for preparing targeted diagnosis and treatment reagents and drugs for prostatic cancer.

Description

technical field [0001] The invention belongs to the technical field of biological targeting, relates to the specific targeting of prostate cancer, in particular to a macrophage membrane-wrapped biomimetic nano drug carrier targeting PSMA and its application. [0002] technical background [0003] Nanomedicine is considered to be one of the most promising anti-tumor strategies in the 21st century, and it has gradually become a hot spot and focus in the research and development of new tumor drugs. Among them, nano-drug carriers can not only increase the stability of drug delivery and improve the The water solubility of the drug; it is also expected that drugs with good anti-tumor activity but poor pharmacokinetics will be included in the candidate category, increasing the flexibility of clinical medication and providing new impetus for clinical diagnosis and treatment of tumors. However, traditional nano-drug delivery systems, such as FDA-approved liposomes, polymers, and album...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K41/00A61K45/00A61K49/00A61K49/04A61K49/18A61P13/08A61P19/08A61P35/00A61P35/04C12N15/867C12N15/62
CPCY02A50/30
Inventor 秦卫军张克英韩东晖温伟红李宇王经纬杨发许超刘少杰
Owner AIR FORCE MEDICAL UNIV
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