Targeted in situ self-assembly augments peptide drug conjugate cell-entry efficiency

IF 12.8 1区医学 Q1 ENGINEERING, BIOMEDICAL

Biomaterials Pub Date : 2021-11-01 DOI:10.1016/j.biomaterials.2021.121139

Man-Di Wang , Da-Yong Hou , Gan-Tian Lv , Ru-Xiang Li , Xing-Jie Hu , Zhi-Jia Wang , Ni-Yuan Zhang , Li Yi , Wan-Hai Xu , Hao Wang

{"title":"Targeted in situ self-assembly augments peptide drug conjugate cell-entry efficiency","authors":"Man-Di Wang , Da-Yong Hou , Gan-Tian Lv , Ru-Xiang Li , Xing-Jie Hu , Zhi-Jia Wang , Ni-Yuan Zhang , Li Yi , Wan-Hai Xu , Hao Wang","doi":"10.1016/j.biomaterials.2021.121139","DOIUrl":null,"url":null,"abstract":"<div><p><span>Peptide drug conjugate (PDC) has emerged as one of the new generations of targeted therapeutics for cancer, which owns the advantages of improved drug targetability and reduced adverse effects compared with traditional chemotherapy. However, the poor permeability of PDC drugs regarding tumor cells is an urgent problem to be solved. Herein, we design a PDC drug molecule, which is composed of three modules: targeting motif (RGD target), assembly motif (GNNNQNY) and cytotoxic payload (CPT molecule). This PDC </span><em>in situ</em><span> forms nanoclusters upon binding cellular receptor, resulting in improved PDC cell-entry efficiency and treatment efficacy. In addition, the PDC shows increased therapeutic efficacy and raises the maximum tolerance dose of the drug in breast and bladder xenografted mice models. This strategy leverages the assembly principle to promote penetration of peptide molecules into cells and increase intracellular drug bioavailability, which is of great significance for the development of PDC drugs in the future.</span></p></div>","PeriodicalId":254,"journal":{"name":"Biomaterials","volume":null,"pages":null},"PeriodicalIF":12.8000,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"22","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomaterials","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0142961221004968","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}

引用次数: 22

Abstract

Peptide drug conjugate (PDC) has emerged as one of the new generations of targeted therapeutics for cancer, which owns the advantages of improved drug targetability and reduced adverse effects compared with traditional chemotherapy. However, the poor permeability of PDC drugs regarding tumor cells is an urgent problem to be solved. Herein, we design a PDC drug molecule, which is composed of three modules: targeting motif (RGD target), assembly motif (GNNNQNY) and cytotoxic payload (CPT molecule). This PDC in situ forms nanoclusters upon binding cellular receptor, resulting in improved PDC cell-entry efficiency and treatment efficacy. In addition, the PDC shows increased therapeutic efficacy and raises the maximum tolerance dose of the drug in breast and bladder xenografted mice models. This strategy leverages the assembly principle to promote penetration of peptide molecules into cells and increase intracellular drug bioavailability, which is of great significance for the development of PDC drugs in the future.

Abstract Image

查看原文本刊更多论文

靶向原位自组装提高了肽药物偶联细胞进入效率

肽药物偶联物(Peptide drug conjugate, PDC)作为新一代肿瘤靶向治疗药物之一，与传统化疗相比，具有药物靶向性提高、不良反应减少等优点。然而PDC药物对肿瘤细胞渗透性差是一个亟待解决的问题。本文设计了一种PDC药物分子，该分子由靶向基序(RGD靶)、组装基序(GNNNQNY)和细胞毒有效载荷(CPT分子)三个模块组成。这种PDC原位结合细胞受体形成纳米团簇，提高了PDC进入细胞的效率和治疗效果。此外，PDC在乳腺和膀胱异种移植小鼠模型中显示出更高的治疗效果，并提高了药物的最大耐受剂量。该策略利用组装原理促进肽分子渗透到细胞内，提高细胞内药物的生物利用度，对未来PDC药物的开发具有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biomaterials 工程技术-材料科学：生物材料

CiteScore

26.00

自引率

2.90%

发文量

565

审稿时长

46 days

期刊介绍： Biomaterials is an international journal covering the science and clinical application of biomaterials. A biomaterial is now defined as a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure. It is the aim of the journal to provide a peer-reviewed forum for the publication of original papers and authoritative review and opinion papers dealing with the most important issues facing the use of biomaterials in clinical practice. The scope of the journal covers the wide range of physical, biological and chemical sciences that underpin the design of biomaterials and the clinical disciplines in which they are used. These sciences include polymer synthesis and characterization, drug and gene vector design, the biology of the host response, immunology and toxicology and self assembly at the nanoscale. Clinical applications include the therapies of medical technology and regenerative medicine in all clinical disciplines, and diagnostic systems that reply on innovative contrast and sensing agents. The journal is relevant to areas such as cancer diagnosis and therapy, implantable devices, drug delivery systems, gene vectors, bionanotechnology and tissue engineering.