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载 cRGD 肽的共价有机框架用于三阴性乳腺癌的精准化疗。

cRGD-Peptide Modified Covalent Organic Frameworks for Precision Chemotherapy in Triple-Negative Breast Cancer.

机构信息

Chemistry Program, New York University Abu Dhabi (NYUAD), Abu Dhabi 129188, United Arab Emirates.

Core Technology Platforms, New York University Abu Dhabi, 129188 Abu Dhabi, United Arab Emirates.

出版信息

ACS Appl Mater Interfaces. 2024 Oct 23;16(42):56676-56695. doi: 10.1021/acsami.4c10812. Epub 2024 Sep 13.

DOI:10.1021/acsami.4c10812
PMID:39267454
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11503616/
Abstract

This study presents the use of nanoscale covalent organic frameworks (nCOFs) conjugated with tumor-targeting peptides for the targeted therapy of triple-negative breast cancer (TNBC). While peptides have previously been used for targeted delivery, their conjugation with COFs represents an innovative approach in this field. In particular, we have developed alkyne-functionalized nCOFs chemically modified with cyclic RGD peptides (Alkyn-nCOF-cRGD). This configuration is designed to specifically target αβ integrins that are overexpressed in TNBC cells. These nCOFs exhibit excellent biocompatibility and are engineered to selectively disintegrate under acidic conditions, allowing for precise and localized drug release in tumor environment. Doxorubicin, a chemotherapeutic agent, has been encapsulated in these nCOFs with high loading efficiency. The therapeutic potential of Alkyn-nCOF-cRGD has been demonstrated in vitro and in vivo models. It shows significantly improved drug uptake and targeted cell death in TNBC, highlighting the efficacy of receptor-mediated endocytosis and pH-controlled drug release. This strategy leverages the unique properties of nCOFs with targeted drug delivery to achieve significant advances in personalized cancer therapy and set a new standard for precision chemotherapeutic delivery.

摘要

本研究提出了使用纳米级共价有机框架（nCOFs）与肿瘤靶向肽缀合，用于三阴性乳腺癌（TNBC）的靶向治疗。虽然肽以前曾被用于靶向递送，但它们与 COFs 的缀合代表了该领域的创新方法。特别是，我们开发了炔基功能化的 nCOFs，其化学修饰有环状 RGD 肽（Alkyn-nCOF-cRGD）。这种结构旨在专门针对在 TNBC 细胞中过度表达的αβ整合素。这些 nCOFs 表现出优异的生物相容性，并经过设计可在酸性条件下选择性解体，从而在肿瘤环境中实现精确和局部的药物释放。阿霉素是一种化疗药物，已被高载药量封装在这些 nCOFs 中。Alkyn-nCOF-cRGD 的治疗潜力已在体外和体内模型中得到证实。它在 TNBC 中显示出显著改善的药物摄取和靶向细胞死亡，突出了受体介导的内吞作用和 pH 控制的药物释放的功效。这种策略利用了 nCOFs 的独特性质与靶向药物递送相结合，在个性化癌症治疗方面取得了重大进展，并为精准化疗药物递送设定了新标准。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/3303f3528b85/am4c10812_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/1f2ec7381db9/am4c10812_0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/b9285886c2a7/am4c10812_0005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/4d9299a8c84f/am4c10812_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/3303f3528b85/am4c10812_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/1f2ec7381db9/am4c10812_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/58cd190f60d1/am4c10812_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/91e4ed032c07/am4c10812_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/6e005f1d2dff/am4c10812_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/b9285886c2a7/am4c10812_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/d144fb6ae6c7/am4c10812_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/f7911ab024d4/am4c10812_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/4d9299a8c84f/am4c10812_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d11/11503616/3303f3528b85/am4c10812_0009.jpg

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