Gao, Z., Mansor, M.H., Winder, N. et al. (4 more authors) (2023) Microfluidic-assisted ZIF-silk-polydopamine nanoparticles as promising drug carriers for breast cancer therapy. Pharmaceutics, 15 (7). 1811. ISSN 1999-4923
Abstract
Metal–organic frameworks (MOFs) are heralded as potential nanoplatforms for biomedical applications. Zeolitic imidazolate framework-8 (ZIF-8), as one of the most well known MOFs, has been widely applied as a drug delivery carrier for cancer therapy. However, the application of ZIF-8 nanoparticles as a therapeutic agent has been hindered by the challenge of how to control the release behaviour of anti-cancer zinc ions to cancer cells. In this paper, we designed microfluidic-assisted core-shell ZIF-8 nanoparticles modified with silk fibroin (SF) and polydopamine (PDA) for sustained release of zinc ions and curcumin (CUR) and tested these in vitro in various human breast cancer cells. We report that microfluidic rapid mixing is an efficient method to precisely control the proportion of ZIF-8, SF, PDA, and CUR in the nanoparticles by simply adjusting total flow rates (from 1 to 50 mL/min) and flow rate ratios. Owing to sufficient and rapid mixing during microfluidic-assisted nanoprecipitation, our designer CUR@ZIF-SF-PDA nanoparticles had a desired particle size of 170 nm with a narrow size distribution (PDI: 0.08), which is much smaller than nanoparticles produced using traditional magnetic stirrer mixing method (over 1000 nm). Moreover, a properly coated SF layer successfully enhanced the capability of ZIF-8 as a reservoir of zinc ions. Meanwhile, the self-etching reaction between ZIF-8 and PDA naturally induced a pH-responsive release of zinc ions and CUR to a therapeutic level in the MDA-MB-231, SK-BR-3, and MCF-7 breast cancer cell lines, resulting in a high cellular uptake efficiency, cytotoxicity, and cell cycle arrest. More importantly, the high biocompatibility of designed CUR@ZIF-SF-PDA nanoparticles remained low in cytotoxicity on AD-293 non-cancer cells. We demonstrate the potential of prepared CUR@ZIF-SF-PDA nanoparticles as promising carriers for the controlled release of CUR and zinc ions in breast cancer therapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
Keywords: | microfluidic-assisted; ZIF-8; silk fibroin; polydopamine; curcumin; nanoparticles; controlled release; MDA-MB-231; SK-BR-3; MCF-7; AD-293 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Funding Information: | Funder Grant number CANCER RESEARCH UK C25574/A24321 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Jul 2023 10:10 |
Last Modified: | 12 Jul 2023 10:10 |
Status: | Published |
Publisher: | MDPI AG |
Refereed: | Yes |
Identification Number: | 10.3390/pharmaceutics15071811 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201395 |