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8. Tri-modal imaging of gold-dotted magnetic nanoparticles for magnetic resonance imaging, computed tomography and intravascular ultrasound: an in vitro study

Author

Kuhn, Joel, primary, Papanastasiou, Giorgos, additional, Tai, Cheuk-Wai, additional, Moran, Carmel M, additional, Jansen, Maurits A, additional, Tavares, Adriana AS, additional, Lennen, Ross J, additional, Corral, Carlos Alcaide, additional, Wang, Chengjia, additional, Thomson, Adrian JW, additional, Berry, Catherine C, additional, and Yiu, Humphrey HP, additional

Published
2020
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9. Tri-modal imaging of gold-dotted magnetic nanoparticles for magnetic resonance imaging, computed tomography and intravascular ultrasound : an in vitro study

Author

Kuhn, Joel, Papanastasiou, Giorgos, Tai, Cheuk-Wai, Moran, Carmel M., Jansen, Maurits A., Tavares, Adriana A. S., Lennen, Ross J., Corral, Carlos Alcaide, Wang, Chengjia, Thomson, Adrian J. W., Berry, Catherine C., Yiu, Humphrey H. P., Kuhn, Joel, Papanastasiou, Giorgos, Tai, Cheuk-Wai, Moran, Carmel M., Jansen, Maurits A., Tavares, Adriana A. S., Lennen, Ross J., Corral, Carlos Alcaide, Wang, Chengjia, Thomson, Adrian J. W., Berry, Catherine C., and Yiu, Humphrey H. P.

Abstract

Aim: To examine the multimodal contrasting ability of gold-dotted magnetic nanoparticles (Au*MNPs) for magnetic resonance (MR), computed tomography (CT) and intravascular ultrasound (IVUS) imaging. Materials & methods: Au*MNPs were prepared by adapting an impregnation method, without using surface capping reagents and characterized (transmission electron microscopy, x-ray diffraction and Fourier-transform infrared spectroscopy) with theirin vitrocytotoxicity assessed, followed by imaging assessments. Results: The contrast-enhancing ability of Au*MNPs was shown to be concentration-dependent across MR, CT and IVUS imaging. The Au content of the Au*MNP led to evident increases of the IVUS signal. Conclusion: We demonstrated that Au*MNPs showed concentration-dependent contrast-enhancing ability in MRI and CT imaging, and for the first-time in IVUS imaging due to the Au content. These Au*MNPs are promising toward solidifying tri-modal imaging-based theragnostics.

Published
2020
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18. Nanoparticle-antagomiR based targeting of miR-31 to induce osterix and osteocalcin expression in mesenchymal stem cells

Author

Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Osorio De Castro Conde, Joao, McCully, Mark, V. Baptista, Pedro, Mullin, Margaret, Dalby, Matthew J., Berry, Catherine C., Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Osorio De Castro Conde, Joao, McCully, Mark, V. Baptista, Pedro, Mullin, Margaret, Dalby, Matthew J., and Berry, Catherine C.

Abstract

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Mesenchymal stem cells are multipotent adult stem cells capable of generating bone, cartilage and fat, and are thus currently being exploited for regenerative medicine. When considering osteogenesis, developments have been made with regards to chemical induction (e.g. differentiation media) and physical induction (e.g. material stiffness, nanotopography), targeting established early transcription factors or regulators such as runx2 or bone morphogenic proteins and promoting increased numbers of cells committing to osteo-specific differentiation. Recent research highlighted the involvement of microRNAs in lineage commitment and terminal differentiation. Herein, gold nanoparticles that confer stability to short single stranded RNAs were used to deliver MiR-31 antagomiRs to both pre-osteoblastic cells and primary human MSCs in vitro. Results showed that blocking miR-31 led to an increase in osterix protein in both cell types at day 7, with an increase in osteocalcin at day 21, suggesting MSC osteogenesis. In addition, it was noted that antagomiR sequence direction was important, with the 5 prime reading direction proving more effective than the 3 prime. This study highlights the potential that miRNA antagomiR-Tagged nanoparticles offer as novel therapeutics in regenerative medicine.

Published
2018

24. The influence of particle size and static magnetic fields on the uptake of magnetic nanoparticles into three dimensional cell-seeded collagen gel cultures

Author

Lewis, Emily E.L., Child, Hannah W., Hursthouse, Andrew, Stirling, David, McCully, Mark, Paterson, David, Mullin, Margaret, and Berry, Catherine C.

Subjects
equipment and supplies, human activities
Abstract

Over recent decades there has been and continues to be major advances in the imaging, diagnosis and potential treatment of medical conditions, by the use of magnetic nanoparticles. However, to date the majority of cell delivery studies employ a traditional 2D monolayer culture. This article aims to determine the ability of various sized magnetic nanoparticles to penetrate and travel through a cell seeded collagen gel model, in the presence or absence of a magnetic field. Three different sized (100, 200, and 500 nm) nanoparticles were employed in the study. The results showed cell viability was unaffected by the presence of nanoparticles over a 24-h test period. The initial uptake of the 100 nm nanoparticle into the collagen gel structure was superior compared to the larger sized nanoparticles under the influence of a magnetic field and incubated for 24 h. Interestingly, it was the 200 nm nanoparticles, which proved to penetrate the gel furthest, under the influence of a magnetic field, during the initial culture stage after 1-h incubation.

Published
2015

26. Significance of the balance between intracellular glutathione and polyethylene glycol for successful release of small interfering RNA from gold nanoparticles

Author

Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Osorio De Castro Conde, Joao, McCully, Mark, Hernandez, Yulan, Hursthouse, Andrew, Stirling, David, Baptista, Pedro V., de la Fuente, Jesus M., Berry, Catherine C., Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Osorio De Castro Conde, Joao, McCully, Mark, Hernandez, Yulan, Hursthouse, Andrew, Stirling, David, Baptista, Pedro V., de la Fuente, Jesus M., and Berry, Catherine C.

Abstract

The therapeutic promise of small interfering RNAs (siRNAs) for specific gene silencing is dependent on the successful delivery of functional siRNAs to the cytoplasm. Their conjugation to an established delivery platform, such as gold nanoparticles, offers tremendous potential for treating diseases and advancing our understanding of cellular processes. Their success or failure is dependent on both the uptake of the nanoparticles into the cells and subsequent intracellular release of the functional siRNA. In this study, utilizing gold nanoparticle siRNA-mediated delivery against C-MYC, we aimed to determine if we could achieve knockdown in a cancer cell line with low levels of intracellular glutathione, and determine the influence, if any, of polyethylene glycol (PEG) ligand density on knockdown, with a view to determining the optimal nanoparticle design to achieve C-MYC knockdown. We demonstrate that, regardless of the PEG density, knockdown in cells with relatively low glutathione levels can be achieved, as well as the possible effect of steric hindrance of PEG on the availability of the siRNA for cleavage in the intracellular environment. Gold nanoparticle uptake was demonstrated via transmission electron microscopy and mass spectroscopy, while knockdown was determined at the protein and physiological levels (cells in S-phase) by in-cell westerns and BrdU incorporation, respectively.

Published
2016

31. Design of Multifunctional Gold Nanoparticles for In Vitro and In Vivo Gene Silencing

Author

Conde, João, primary, Ambrosone, Alfredo, additional, Sanz, Vanesa, additional, Hernandez, Yulan, additional, Marchesano, Valentina, additional, Tian, Furong, additional, Child, Hannah, additional, Berry, Catherine C., additional, Ibarra, M. Ricardo, additional, Baptista, Pedro V., additional, Tortiglione, Claudia, additional, and de la Fuente, Jesus M., additional

Published
2012
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32. Working Together: The Combined Application of a Magnetic Field and Penetratin for the Delivery of Magnetic Nanoparticles to Cells in 3D

Author

Child, Hannah W., primary, del Pino, Pablo A., additional, De La Fuente, Jesus M., additional, Hursthouse, Andrew S., additional, Stirling, David, additional, Mullen, Margaret, additional, McPhee, Gordon M., additional, Nixon, Colin, additional, Jayawarna, Vineetha, additional, and Berry, Catherine C., additional

Published
2011
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49. Elucidating the Function of Penetratin and a Static Magnetic Field in Cellular Uptake of Magnetic Nanoparticles.

Author

Chaudhary, Suman, Smith, Carol Anne, Pino, Pablo del, de la Fuente, Jesus M., Mullin, Margaret, Hursthouse, Andrew, Stirling, David, and Berry, Catherine C.

Subjects
MAGNETIC fields, MAGNETIC nanoparticles, INDUCTIVELY coupled plasma mass spectrometry, TRANSMISSION electron microscopy, WESTERN immunoblotting, ENDOCYTOSIS, CAVEOLINS, CLATHRIN
Abstract

Nanotechnology plays an increasingly important role in the biomedical arena. In particular, magnetic nanoparticles (mNPs) have become important tools in molecular diagnostics, in vivo imaging and improved treatment of disease, with the ultimate aim of producing a more theranostic approach. Due to their small sizes, the nanoparticles can cross most of the biological barriers such as the blood vessels and the blood brain barrier, thus providing ubiquitous access to most tissues. In all biomedical applications maximum nanoparticle uptake into cells is required. Two promising methods employed to this end include functionalization of mNPs with cell-penetrating peptides to promote efficient translocation of cargo into the cell and the use of external magnetic fields for enhanced delivery. This study aimed to compare the effect of both penetratin and a static magnetic field with regards to the cellular uptake of 200 nm magnetic NPs and determine the route of uptake by both methods. Results demonstrated that both techniques increased particle uptake, with penetratin proving more cell specific. Clathrinmedicated endocytosis appeared to be responsible for uptake as shown via PCR and western blot, with Pitstop 2 (known to selectively block clathrin formation) blocking particle uptake.Interestingly, it was further shown that a magnetic field was able to reverse or overcome the blocking, suggesting an alternative route of uptake. [ABSTRACT FROM AUTHOR]

Published
2013
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50. Design of Multifunctional Gold Nanoparticles for In Vitroand In VivoGene Silencing

Author

Conde, João, Ambrosone, Alfredo, Sanz, Vanesa, Hernandez, Yulan, Marchesano, Valentina, Tian, Furong, Child, Hannah, Berry, Catherine C., Ibarra, M. Ricardo, Baptista, Pedro V., Tortiglione, Claudia, and de la Fuente, Jesus M.

Abstract

Over the past decade, the capability of double-stranded RNAs to interfere with gene expression has driven new therapeutic approaches. Since small interfering RNA (siRNAs, 21 base pair double-stranded RNA) was shown to be able to elicit RNA interference (RNAi), efforts were directed toward the development of efficient delivery systems to preserve siRNA bioactivity throughout the delivery route, from the administration site to the target cell. Here we provide evidence of RNAi triggering, specifically silencing c-myc protooncogene, viathe synthesis of a library of novel multifunctional gold nanoparticles (AuNPs). The efficiency of the AuNPs is demonstrated using a hierarchical approach including three biological systems of increasing complexity: in vitrocultured human cells, in vivoinvertebrate (freshwater polyp, Hydra), and in vivovertebrate (mouse) models. Our synthetic methodology involved fine-tuning of multiple structural and functional moieties. Selection of the most active functionalities was assisted step-by-step through functional testing that adopted this hierarchical strategy. Merging these chemical and biological approaches led to a safe, nonpathogenic, self-tracking, and universally valid nanocarrier that could be exploited for therapeutic RNAi.

Published
2012
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