Delivery and cytotoxicity of doxorubicin and temozolomide to primary glioblastoma cells using gold nanospheres and gold nanorods
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Jyoti Verma
Verma is a final year joint doctoral candidate between Harvard Medical School and University of Amsterdam. She is a passionate nanotechnologist with a deep interest in the development of novel cancer theranostic devices based on inorganic nanoparticles. She has extensive experience in synthesizing and characterizing inorganic nanoparticles including gold and silver nanoparticles. She has generated more than 10 papers and invented 2 technologies in the last 7 years. She has been awarded/offered many prestigious pre doctoral and doctoral scholarship /fellowship awards including McDiarmid scholarship award, University of Groningen doctoral fellowship and Biocomposites (NZ) pre doctoral fellowship award.
Henk graduated from the HU (higher school for life sciences and chemistry) in Utrecht in Cellbiology and started as a EM technician at the department of cellbiology, UVA (Amsterdam) in 1976. Currently he is working at the core facility cellular imaging as EM operator/floor manager for the Electron Microscopy center Amsterdam (EMCA). His work consists partly of advising, supporting and assisting researchers who want to integrade TEM and SEM techniques within their own reseach projects and partly from managing the EM equipment in the department.
Sumit Lal is an expert in the field of inorganic nanomedicine. His areas of investigation include utilization of titanium dioxide, gold and iron oxide nanoparticles (SPIONs) for development of novel drug delivery platforms, medical implants, biosensors and lab on a chip platform. He has generated more than 20 research articles and participated in more than $1M funding in the past 5 years. He is the recipient of prestigious John Gavin Fellowship by Genesis Energy, New Zealand in 2012. To-date, he has been awarded $590,000 in the form of 8 funding awards that include competitively won fellowships and scholarships. He is on the editorial board of Journal of Biomimetics, Biomaterials, and Tissue Engineering, OMICS and Research Journal of Materials Research and Technology, Elsevier. He is also peer reviewer for more than 10 journals including Biomaterials (IF: 8.5), Nature Biotechnology (IF: 31) and Advance functional Materials (IF: 10). He is presently a Junior Faculty at Harvard Medical School. Prior to this, he completed three postdoctoral assignments (fellowships) at The Department of Cell Biology, Harvard Medical School and Nephrology Division, Department of Medicine, Massachusetts General Hospital and Brigham & Women’s Hospital. He holds PhD in Chemistry from, New Zealand’s leading university, The University of Auckland.
and
Cornelis J.F. Van Noorden
Ron Van Noorden was born in 1951 and grew up in the south-western part of The Netherlands close to the North Sea shores and the Belgian border. He went to Amsterdam to become a medical biology student at the University of Amsterdam in 1971. His student years ended in 1978 (cum laude). He became PhD student (PhD in 1983), lecturer (1983–1986), associate professor (1986–1997), full professor in cell biology and histology (1997-present) and chairman (1993–present) of the Department of Cell Biology & Histology of the Academic Medical Center at the University of Amsterdam. His research was always focused on activity of proteins and particularly enzymes in their natural microenvionment, the cell or the extracellular matrix, in pathophysiological conditions such as arthritis, invasion and metastasis of cancer and now brain tumors (glioblastoma) and blindness due to diabetes (diabetic retinopathy). He published almost 300 peer reviewed papers and has been promotor of 27 PhD students so far. He won the Robert Feulgen Prize of the Society for Histochemistry in 1987 together with Roger Butcher for their contribution to quantitative analysis of enzyme activity in situ, he presented the first Piet Van Duijn Lecture of the Dutch Foundation Histochemistry in Kyoto, Japan, 1996 on live cell imaging and in 2008 he won the David Glick Award of the International Federation of Societies for Histochemistry and Cytochemistry.
Abstract
Nanoparticles with coating entrapping a chemotherapeutic drug for delivery have not been tested for their cytotoxic effects in in-vitro glioblastoma cell cultures to increase treatment efficacy. Therefore, we synthesized silica-coated gold nanorods and gold nanospheres that were loaded with doxorubicin or temozolomide. The morphology of the nanoparticles was characterized using transmission electron microscopy (TEM), the molecular structure was characterized using infrared spectroscopy and in vitro efficacy was determined using glioblastoma cell cultures. TEM analysis showed that gold nanorods had a length of 49–65 nm and a diameter of 8.5–14 nm whereas gold nanospheres had a diameter of 9.5–37 nm. Infrared spectroscopy of doxorubicin and temozolomide and the silica coating revealed molecular fingerprints such as bending, stretching and vibrations of chemical bonds that confirmed the presence of silica coating and drug loading of the gold nanoparticles. In the biological assessment of the effects of drug-loaded gold nanoparticles on primary glioblastoma cell cultures, cytotoxicity, viability and the ratio of cyototoxicity and viability were used as parameters to analyze the effects on the cells of drug delivery via gold nanoparticles on the cells. Our data suggest that doxorubicin in the concentration range of 0.12–3.16 μM when delivered using both gold nanorods and nanospheres induced a 3.8–5.5-fold increased cytotoxicity in comparison to direct delivery. Temozolomide in the concentration range of 4.6–115 μM when delivered by either type of gold nanoparticles induced a 2–4-fold increased cytotoxicity in comparison to direct delivery. Nanospheres were more effective in delivery and cytotoxicity of doxorubicin and temozolomide to glioblastoma cells than gold nanorods. Our data suggest that gold nanoparticles and in particular gold nanospheres are more effective in delivery of doxorubicin and temozolomide to primary glioblastoma cells in culture than direct delivery.
About the authors
Verma is a final year joint doctoral candidate between Harvard Medical School and University of Amsterdam. She is a passionate nanotechnologist with a deep interest in the development of novel cancer theranostic devices based on inorganic nanoparticles. She has extensive experience in synthesizing and characterizing inorganic nanoparticles including gold and silver nanoparticles. She has generated more than 10 papers and invented 2 technologies in the last 7 years. She has been awarded/offered many prestigious pre doctoral and doctoral scholarship /fellowship awards including McDiarmid scholarship award, University of Groningen doctoral fellowship and Biocomposites (NZ) pre doctoral fellowship award.
Henk graduated from the HU (higher school for life sciences and chemistry) in Utrecht in Cellbiology and started as a EM technician at the department of cellbiology, UVA (Amsterdam) in 1976. Currently he is working at the core facility cellular imaging as EM operator/floor manager for the Electron Microscopy center Amsterdam (EMCA). His work consists partly of advising, supporting and assisting researchers who want to integrade TEM and SEM techniques within their own reseach projects and partly from managing the EM equipment in the department.
Sumit Lal is an expert in the field of inorganic nanomedicine. His areas of investigation include utilization of titanium dioxide, gold and iron oxide nanoparticles (SPIONs) for development of novel drug delivery platforms, medical implants, biosensors and lab on a chip platform. He has generated more than 20 research articles and participated in more than $1M funding in the past 5 years. He is the recipient of prestigious John Gavin Fellowship by Genesis Energy, New Zealand in 2012. To-date, he has been awarded $590,000 in the form of 8 funding awards that include competitively won fellowships and scholarships. He is on the editorial board of Journal of Biomimetics, Biomaterials, and Tissue Engineering, OMICS and Research Journal of Materials Research and Technology, Elsevier. He is also peer reviewer for more than 10 journals including Biomaterials (IF: 8.5), Nature Biotechnology (IF: 31) and Advance functional Materials (IF: 10). He is presently a Junior Faculty at Harvard Medical School. Prior to this, he completed three postdoctoral assignments (fellowships) at The Department of Cell Biology, Harvard Medical School and Nephrology Division, Department of Medicine, Massachusetts General Hospital and Brigham & Women’s Hospital. He holds PhD in Chemistry from, New Zealand’s leading university, The University of Auckland.
Ron Van Noorden was born in 1951 and grew up in the south-western part of The Netherlands close to the North Sea shores and the Belgian border. He went to Amsterdam to become a medical biology student at the University of Amsterdam in 1971. His student years ended in 1978 (cum laude). He became PhD student (PhD in 1983), lecturer (1983–1986), associate professor (1986–1997), full professor in cell biology and histology (1997-present) and chairman (1993–present) of the Department of Cell Biology & Histology of the Academic Medical Center at the University of Amsterdam. His research was always focused on activity of proteins and particularly enzymes in their natural microenvionment, the cell or the extracellular matrix, in pathophysiological conditions such as arthritis, invasion and metastasis of cancer and now brain tumors (glioblastoma) and blindness due to diabetes (diabetic retinopathy). He published almost 300 peer reviewed papers and has been promotor of 27 PhD students so far. He won the Robert Feulgen Prize of the Society for Histochemistry in 1987 together with Roger Butcher for their contribution to quantitative analysis of enzyme activity in situ, he presented the first Piet Van Duijn Lecture of the Dutch Foundation Histochemistry in Kyoto, Japan, 1996 on live cell imaging and in 2008 he won the David Glick Award of the International Federation of Societies for Histochemistry and Cytochemistry.
Acknowledgments
The authors acknowledge the Van Leeuwenhoek Centre for Advanced Microscopy, Academic Medical Center, University of Amsterdam for support in the TEM analysis reported in this study.
Conflict of interest statement: Authors state no conflict of interest statement. All authors have read the journal’s Publication ethics and publication malpractice statement available at the journal’s website and hereby confirm that they comply with all its parts applicable to the present scientific work.
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©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- In this issue
- Guest Editorial
- Nanotheranostics: is integrating therapeutics with diagnostics enough?
- What’s Up?
- What’s up in nanomedicine?
- Special section Nanotheranostics
- Review
- Intelligent drug delivery systems for the treatment of solid tumors
- Original Articles
- Ultrasound-induced doxorubicin release from folate-targeted and non-targeted P105 micelles: a modeling study
- Effect of pH, ultrasound frequency and power density on the release of calcein from stealth liposomes
- Meeting Report
- Nanotheranostics: realizing the great promise?
- Regular contributions
- Original Article
- Delivery and cytotoxicity of doxorubicin and temozolomide to primary glioblastoma cells using gold nanospheres and gold nanorods
- Opinion Paper
- How organizers of scientific meetings and journal editors could facilitate transfer of nanomedicine into the clinic
Articles in the same Issue
- Frontmatter
- In this issue
- Guest Editorial
- Nanotheranostics: is integrating therapeutics with diagnostics enough?
- What’s Up?
- What’s up in nanomedicine?
- Special section Nanotheranostics
- Review
- Intelligent drug delivery systems for the treatment of solid tumors
- Original Articles
- Ultrasound-induced doxorubicin release from folate-targeted and non-targeted P105 micelles: a modeling study
- Effect of pH, ultrasound frequency and power density on the release of calcein from stealth liposomes
- Meeting Report
- Nanotheranostics: realizing the great promise?
- Regular contributions
- Original Article
- Delivery and cytotoxicity of doxorubicin and temozolomide to primary glioblastoma cells using gold nanospheres and gold nanorods
- Opinion Paper
- How organizers of scientific meetings and journal editors could facilitate transfer of nanomedicine into the clinic
