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

Autor: Singla P; Department of Chemical Engineering, The University of Manchester, Engineering building A, East Booth Street, Oxford Road, Manchester, M13 9PL, UK.; School of Engineering, Newcastle University, Merz Court, Claremont Road, Newcastle Upon Tyne, NE1 7RU, UK.; Center for Cancer Research, NU Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK., Broughton T; Center for Cancer Research, NU Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.; Immune Regulation Laboratory, NU Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.; NIHR, Biomedical Research Centre, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK., Sullivan MV; Department of Chemistry, University of Sheffield, Dainton Building, Sheffield, S3 7HF, UK., Garg S; Department of Chemical Engineering, The University of Manchester, Engineering building A, East Booth Street, Oxford Road, Manchester, M13 9PL, UK.; School of Engineering, Newcastle University, Merz Court, Claremont Road, Newcastle Upon Tyne, NE1 7RU, UK.; Center for Cancer Research, NU Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK., Berlinguer-Palmini R; The Bio-Imaging Unit, Medical School, Newcastle University, William Leech Building, Newcastle Upon Tyne, NE2 4HH, UK., Gupta P; Centre for 3D models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, W1W 7TY, UK., Smith KJ; Center for Cancer Research, NU Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.; Immune Regulation Laboratory, NU Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK., Gardner B; Center for Cancer Research, NU Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.; Immune Regulation Laboratory, NU Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK., Canfarotta F; MIP Discovery, The Exchange Building, Colworth Park, Sharnbrook, Bedford, MK44 1LQ, UK., Turner NW; Department of Chemistry, University of Sheffield, Dainton Building, Sheffield, S3 7HF, UK., Velliou E; Centre for 3D models of Health and Disease, Division of Surgery and Interventional Science, University College London, London, W1W 7TY, UK., Amarnath S; Center for Cancer Research, NU Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.; Immune Regulation Laboratory, NU Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.; NIHR, Biomedical Research Centre, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK., Peeters M; Department of Chemical Engineering, The University of Manchester, Engineering building A, East Booth Street, Oxford Road, Manchester, M13 9PL, UK.; School of Engineering, Newcastle University, Merz Court, Claremont Road, Newcastle Upon Tyne, NE1 7RU, UK.; Center for Cancer Research, NU Cancer, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, NE2 4HH, UK.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Sep; Vol. 11 (36), pp. e2309976. Date of Electronic Publication: 2024 Jul 08.
DOI: 10.1002/advs.202309976
Abstrakt: 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.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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