Polydopamine-coated nanocomposite theranostic implants for localized chemotherapy and MRI imaging

Ziwei Zhang; Lorna Smith; Wenyue Li; Liang Jiang; Fenglei Zhou; Gemma-Louise Davies; Gareth R Williams

doi:10.1016/j.ijpharm.2022.121493

Polydopamine-coated nanocomposite theranostic implants for localized chemotherapy and MRI imaging

Int J Pharm. 2022 Mar 5:615:121493. doi: 10.1016/j.ijpharm.2022.121493. Epub 2022 Jan 19.

Authors

Ziwei Zhang¹, Lorna Smith², Wenyue Li³, Liang Jiang³, Fenglei Zhou⁴, Gemma-Louise Davies⁵, Gareth R Williams⁶

Affiliations

¹ UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; UCL Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK.
² Centre for Medical Imaging, Division of Medicine, University College London, 43-45 Foley Street, London W1W 7TS, UK.
³ College of Textiles and Clothing, Qingdao University, Qingdao 266071, China.
⁴ UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK; College of Textiles and Clothing, Qingdao University, Qingdao 266071, China; Department of Medical Physics and Biomedical Engineering, University College London, Gower Street, London WC1E 6BT, UK. Electronic address: fenglei.zhou@ucl.ac.uk.
⁵ UCL Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK. Electronic address: gemma-louise.davies@ucl.ac.uk.
⁶ UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK. Electronic address: g.williams@ucl.ac.uk.

PMID: 35065209
DOI: 10.1016/j.ijpharm.2022.121493

Abstract

Sustained and localized delivery of chemotherapeutics in postoperative cancer treatment leads to a radical improvement in prognosis and a much decreased risk of tumor recurrence. In this work, polydopamine (PDA)-coated superparamagnetic iron oxide nanoparticle (SPION)-loaded polycaprolactone and poly(lactic-co-glycolic acid) fibers were developed as a potential implant to ensure safe and sustained release of the chemotherapeutic drug methotrexate (MTX), as well as provide local contrast for magnetic resonance imaging (MRI). Fibres were prepared by co-axial electrospinning and loaded with MTX-layered double hydroxide (LDH) nanocomposites in the core, yielding organic-inorganic hybrids ranging from 1.23 to 1.48 µm in diameter. After surface coating with PDA, SPIONs were subsequently loaded on the fibre surface and found to be evenly distributed, providing high MRI contrast. In vitro drug release studies showed the PDA coated fibres gave sustained release of MTX over 18 days, and the release profile is responsive to conditions representative of the tumor microenvironment such as slightly acidic pH values or elevated concentrations of the reducing agent glutathione (GSH). In vitro studies with Caco-2 and A549 cells showed highly effective killing with the PDA coated formulations, which was further enhanced at higher levels of GSH. The fibres hence have the potential to act as an implantable drug-eluting platform for the sustained release of cytotoxic agents within a tumor site, providing a novel treatment option for post-operative cancer patients.

Keywords: Cancer; Electrospun nanofibres; Implant; Polydopamine; Theranostic.

MeSH terms

Caco-2 Cells
Humans
Indoles
Magnetic Resonance Imaging
Nanocomposites*
Polymers
Precision Medicine*
Theranostic Nanomedicine

Substances

Indoles
Polymers
polydopamine