Singla, P., Broughton, T., Sullivan, M.V. orcid.org/0000-0002-1771-8268 et al. (10 more authors) (2024) Double imprinted nanoparticles for sequential membrane‐to‐nuclear drug delivery. Advanced Science, 11 (36). 2309976. ISSN 2198-3844
Abstract
Efficient and site‐specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody‐drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life‐threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost‐effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor‐mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof‐of‐concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three‐dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited: https://creativecommons.org/licenses/by/4.0/ |
Keywords: | biomimetic 3D cancer models; breast cancer; chemotherapy; imprinted nanoparticles; precision nanomedicine; targeted drug delivery |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > Department of Chemistry (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Jul 2024 13:00 |
Last Modified: | 22 Nov 2024 16:37 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/advs.202309976 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:214782 |