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Research Article

Designed fabrication of active tumor targeting covalent organic framework nanotherapeutics via a simple post-synthetic strategy

Yue Yu1,2( ), Guoxin Zhang3, Zhongping Li4,5( ), Jia Wang2, Yang Liu6, Rahul Bhardwaj4, Renu Wadhwa2, Yuki Nagao4, Mototada Shichiri1,2, Ran Gao3( )
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Osaka 563-8577, Japan
AIST-INDIA DAILAB, DBT-AIST International Center for Translational & Environmental Research (DAICENTER), AIST, Tsukuba, Ibaraki 305-8565, Japan
Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, NHC Key Laboratory of Human Disease Comparative Medicine, National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical Collage, Beijing 100021, China
School of Materials Science, Japan Advanced Institute of Science and Technology, Ishikawa 923-1211, Japan
Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Republic of Korea
Flexible 3D System Integration Laboratory, SANKEN, Osaka University, Osaka 567-0047, Japan
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Graphical Abstract

A highly cancer targeting covalent organic framework (COF), that shows low toxicity, well-dispersibility, and high drug loading capacity, is reported. Comparing to drug administrated alone, the folate-functionalized COF nanocarrier significantly enhances the selectivity and cytotoxicity of its loaded drug, resulting in nearly 7-fold decrease in final tumor volume. Such exceptional antitumor activity indicates great potentials of COF-based nanomedicine towards targeted cancer therapy.

Abstract

Developing agents that can accurately differentiate tumors from normal healthy tissues is of utmost importance for safe cancer therapy. Active targeting has been considered as an effective technique for tumor recognition. In this work, we demonstrate a folate-functionalized nanoscale covalent organic framework (FATD nCOF) highly specific to cancer cells through active targeting of their enriched folate receptors (FRs). The FATD nCOF prepared by simple post-synthetic modification of the COF surface defeats disperses well in water and exhibits a high loading capacity for various anticancer drugs. The biocompatible FATD nCOF is selectively internalized by FR-harboring cancer cells and consequently augments the efficacy of the loaded drug, Withaferin A (Wi-A), for targeted cancer cell killing. In biomolecular mechanism studies, Wi-A-loaded FATD (FATD@Wi-A) nanocomposites show remarkably a higher rate of apoptosis in FR-enriched cancer cells. Comparative analyses of FR-positive and FR-negative tumor xenografts reveal enhanced selective antitumor activity of FATD@Wi-A nanotherapeutics. Taken together, the study findings suggest that FATD nCOF holds great promise for active targeting of tumors in vivo. Our simple yet effective technology might be valuable for creating new state-of-the-art COFs for chemical and biomedical applications.

Keywords

covalent organic frameworkactive targetingfolate receptordrug deliverycancer therapy

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Nano Research
Volume 16 Issue 5,
May 2023
Pages 7085-7094
DOI: 10.1007/s12274-022-5265-7
Cite this article:
Yu Y, Zhang G, Li Z, et al. Designed fabrication of active tumor targeting covalent organic framework nanotherapeutics via a simple post-synthetic strategy. Nano Research, 2023, 16(5): 7085-7094. https://doi.org/10.1007/s12274-022-5265-7
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Received: 30 June 2022
Revised: 28 October 2022
Accepted: 31 October 2022
Published: 03 January 2023
© Tsinghua University Press 2022
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