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Double Imprinted Nanoparticles for Sequential Membrane-to-Nuclear Drug Delivery

Lookup NU author(s): Dr Pankaj Singla, Dr Tommy Broughton, Saweta Garg, Dr Rolando Berlinguer PalminiORCiD, Dr Katie SmithORCiD, Ben Gardner, Dr Shoba AmarnathORCiD, Professor Marloes Peeters

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH. 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.


Publication metadata

Author(s): Singla P, Broughton T, Sullivan MV, Garg S, Berlinguer-Palmini R, Gupta P, Smith KJ, Gardner B, Canfarotta F, Turner NW, Velliou E, Amarnath S, Peeters M

Publication type: Article

Publication status: Published

Journal: Advanced Science

Year: 2024

Pages: ePub ahead of Print

Online publication date: 08/07/2024

Acceptance date: 14/06/2024

Date deposited: 15/07/2024

ISSN (electronic): 2198-3844

Publisher: John Wiley and Sons Inc.

URL: https://doi.org/10.1002/advs.202309976

DOI: 10.1002/advs.202309976

Data Access Statement: The data that support the findings of this study are available in the supplementary material of this article.


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Funding

Funder referenceFunder name
European Union Horizon 2020
MR/V028553/1
MRC
Newcastle Wellcome Trust Translational Partnership (NWTTP)

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