Research Article

In vitro evaluation of a hybrid drug-delivery nanosystem for fibrosis prevention in cell therapy for Type 1 diabetes

School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

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Prakriti Siwakoti

School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

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Ziqing Du

School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

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Matthew Padula

School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

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Guochen Bao

Institute for Biomedical Materials & Devices, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

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Bernard E Tuch

https://orcid.org/0000-0003-1472-0394

Department of Diabetes, Central Clinical School, Faculty of Medicine, Nursing & Health Sciences, Monash University, Victoria, 3004, Australia

Australian Foundation for Diabetes Research, 2000, NSW, Australia

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Xiaoxue Xu

*Author for correspondence:

E-mail Address: XiaoxueHelen.Xu@uts.edu.au

https://orcid.org/0000-0002-2598-3766

School of Mathematical and Physical Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW, 2007, Australia

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Lana McClements

**Author for correspondence:

E-mail Address: lana.mcclements@uts.edu.au

https://orcid.org/0000-0002-4911-1014

School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

Institute for Biomedical Materials & Devices, Faculty of Science, University of Technology Sydney, Ultimo, NSW, 2007, Australia

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Published Online:20 Mar 2023https://doi.org/10.2217/nnm-2022-0231

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Abstract

Background: Implantation of insulin-secreting cells has been trialed as a treatment for Type 1 diabetes mellitus; however, the host immunogenic response limits their effectiveness. Methodology: The authors developed a core-shell nanostructure of upconversion nanoparticle-mesoporous silica for controlled local delivery of an immunomodulatory agent, MCC950, using near-infrared light and validated it in in vitro models of fibrosis. Results: The individual components of the nanosystem did not affect the proliferation of insulin-secreting cells, unlike fibroblast proliferation (p < 0.01). The nanosystem is effective at releasing MCC950 and preventing fibroblast differentiation (p < 0.01), inflammation (IL-6 expression; p < 0.05) and monocyte adhesion (p < 0.01). Conclusion: This MCC950-loaded nanomedicine system could be used in the future together with insulin-secreting cell implants to increase their longevity as a curative treatment for Type 1 diabetes mellitus.

Plain language summary

This work describes a new drug-delivery system that can release an immunomodulatory drug in a controlled manner and prevent fibrosis, which is part of the immune response when a foreign body is implanted. This system can be particularly useful for insulin-secreting cell implants, used to replace multiple daily injections of insulin and improve the quality of life of people with Type 1 diabetes mellitus. By preventing the immune response that leads to fibrosis, the longevity of these cellular implants can be extended without the need for frequent replacement procedures. This innovative nanosystem can release the required amount of immunomodulatory drug, which could be stimulated with the use of special light, hence showing the ability for local and extended delivery. This type of system has the potential to reduce the side effects associated with oral daily administration of immunomodulatory agents in people with Type 1 diabetes mellitus.

Tweetable abstract

In this article, the authors describe an innovative approach for the controlled release of an immunomodulatory agent based on an upconversion nanomedicine system that could be explored for the prevention of fibrosis in insulin-secreting cell implant treatment for Type 1 diabetes mellitus.

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Keywords:

Papers of special note have been highlighted as: • of interest

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Vol. 18, No. 1

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History

Received 6 September 2022

Accepted 1 February 2023

Published online 20 March 2023

Published in print January 2023

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Keywords

Author contributions

C Rennie performed the experiments, data analysis and wrote the manuscript. Y Huang, P Siwakoti, Z Du and M Padula contributed to the experimental design and performance. BE Tuch, X Xu and L McClements conceived the study design or made significant contribution to the study design, data analysis and/or interpretation and manuscript writing. X Xu and L McClements conceived the study, designed the experiments and supervised; C Rennie, Y Huang and P Siwakoti wrote the manuscript. All authors reviewed and approved the final manuscript.

Financial & competing interests disclosure

The work was funded by a JDRF innovative grant (1-INO-2020-914-A). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Data sharing statement

The data that support the findings of this study are available upon reasonable request from the corresponding authors, L McClements and X Xu.

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