Anas Tomeh, M., Hadianamrei, R., Sun, W. et al. (3 more authors) (2021) Stiffness-tuneable nanocarriers for controlled delivery of ASC-J9 into colorectal cancer cells. Journal of Colloid and Interface Science, 594. pp. 513-521. ISSN 0021-9797
Abstract
Hypothesis
One of the main challenges in cancer therapy is the poor water solubility of many anticancer drugs which results in low bioavailability at the tumour sites and reduced efficacy. The currently available polymer-based anticancer drug delivery systems often suffer from low encapsulation efficiency, uncontrolled release, and lack of long-term stability. Herein, we report the development of novel stiffness-tuneable core–shell nanocarriers composed of naturally derived polymers silk fibroin (SF) and sodium alginate (SA) inside a liposomal shell for enhanced cellular uptake and controlled release of hydrophobic anticancer agent ASC-J9 (Dimethylcurcumin). It is anticipated that the stiffness of the nanocarriers has a significant effect on their cellular uptake and anticancer efficacy.
Experiments
The nanocarriers were prepared by thin film hydration method followed by extrusion and cross-linking of SA to obtain a uniform size and shape, avoiding harsh processing conditions. The structural transformation of SF in the nanocarriers induced by SA crosslinking was determined using Fourier transform infrared (FTIR) spectroscopy. The size, zeta potential, morphology and stiffness of the nanocarriers were measured using dynamic light scattering (DLS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). Drug loading and release were measured using UV–Vis spectrophotometry. The cellular uptake and anticancer efficacy of the nanocarriers were studied in HCT 116 human colorectal adenocarcinoma cells and 3D tumour spheroids using high content microscopy.
Findings
The synthesized nanocarriers had high encapsulation efficiency (62–78%) and were physically stable for up to 5 months at 4 ˚C. The release profile of the drug from the nanocarriers was directed by their stiffness and was easily tuneable by changing the ratio of SF to SA in the core. Furthermore, the designed nanocarriers improved the cellular uptake and anticancer activity of ASC-J9, and enhanced its tumour penetration in HCT 116 3D colorectal cancer spheroids. These findings suggest that the designed core–shell nanocarriers can be used as a highly efficient drug delivery system for cancer therapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Nanocarrier; Silk fibroin; Particle stiffness; Controlled release; Drug delivery; Anticancer; ASC-J9 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Chemical and Biological Engineering (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/N007174/1 ENGINEERING AND PHYSICAL SCIENCE RESEARCH COUNCIL EP/N023579/1 ROYAL SOCIETY RG160662 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 30 Mar 2021 15:24 |
Last Modified: | 30 Mar 2021 15:24 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.jcis.2021.03.086 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:172633 |