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Incorporation of Ophiobolin A into Novel Chemoembolization Particles for Cancer Cell Treatment

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ABSTRACT

Purpose

To design and synthesize chemoembolization particles for the delivery of Ophiobolin A (OphA), a promising fungal-derived chemotherapeutic, directly at the tumour location. To investigate cell death mechanism of OphA on a Rhabdomyosarcoma cancer (RD) cell line. Rhabdomyosarcoma is the most common soft tissue sarcoma in children; with a 5-year survival rate of between 30 and 65%.

Methods

Multimodal chemoembolization particles were prepared by sintering mesoporous silica nanoparticles, prepared by the sol-gel method, onto the surface of polystyrene microspheres, prepared by suspension copolymerisation. The chemoembolization particles were subsequently loaded with OphA. The effects of OphA in vitro were characterised by flow cytometry and nanoparticle tracking analysis (NanoSight).

Results

High loading of OphA onto the chemoembolization particles was achieved. The subsequent release of OphA onto RD cells in culture showed a 70% reduction in cell viability. OphA caused RD cells to round up and their membrane to bleb and caused cell death via apoptosis. OphA caused both an increase in the number of microvesicles produced and an increase in DNA content within these microvesicles.

Conclusions

The prepared chemoembolization particles showed good efficacy against RD cells in culture.

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Abbreviations

AIBN:

Azobisisobutyronitrile

CTAB:

Cetyl trimethylammonium bromide

CytoD:

CytochalasinD

DCM:

Dichloromethane

DMEM:

Dulbecco’s Modified Eagle’s Medium

EGDMA:

Ethylene glycol dimethacrylate

Em:

Emission

Ex:

Excitation

GFP:

Green fluorescent protein

HMSNP:

Hexagonal mesoporous silica nanoparticles

LC:

Liquid chromatography

mtDNA:

Mitochondrial DNA

NTA:

Nanoparticle tracking analysis

OphA:

Ophiobolin A

PBS:

Phosphate buffered saline

PI:

Propidium iodide

PS:

Polystyrene spheres

PS-HMSNP:

Polystyrene-(hexagonal mesoporous silica nanoparticle) composite particles

PVA:

Poly(vinyl alcohol)

RD:

Rhabdomyosarcoma cancer cell line

RMS:

Rhabdomyosarcoma

SD:

Standard deviation

SEM:

Scanning electron microscopy

TEM:

Transmission electron microscopy

TEOS:

Tetraethyl orthosilicate

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ACKNOWLEDGMENTS AND DISCLOSURES

Xinyue Huang is thanked for the RD cells expressing GFP and Begbroke Nano is thanked for access to materials characterisation equipment. Neil Young is thanked for training and advice with regards to TEM. Dr. Maurizio Vurro and Maria Chira Zonno (Istituto di Scienze delle Produzioni Alimentari, CNR, Italy) are thanked for supplying culture filtrates of Drechslera gigantea as well as Dr. Fabiana Avolio (Dipartimento di Scienze Chimiche, Università di Napoli Federico II, Napoli, Italy) for her collaboration in Ophiobolin A purification. R. Morrison is funded by RCUK Digital Economy Programme grant number EP/G036861/1 (Oxford Centre for Doctoral Training in Healthcare Innovation). R. Kiss is a director of research with the Fonds National de la Recherche Scientifique (FNRS-FRS; Belgium). H. Townley would like to thank the Williams Fund for continuing support.

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Authors and Affiliations

  1. Department of Engineering Science, Oxford University, Parks Road, Oxford, UK

    Rachel Morrison & Helen Townley

  2. Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford University, Oxford, UK

    Chris Gardiner & Helen Townley

  3. Dipartimento di Scienze Chimiche, Università di Napoli Federico II Complesso Universitario Monte Sant’Angelo, Via Cintia 4, 80126, Napoli, Italy

    Antonio Evidente

  4. Laboratoire de Cancérologie et de Toxicologie Expérimentale, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium

    Robert Kiss

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  1. Rachel Morrison
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  5. Helen Townley
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Corresponding author

Correspondence to Helen Townley.

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Morrison, R., Gardiner, C., Evidente, A. et al. Incorporation of Ophiobolin A into Novel Chemoembolization Particles for Cancer Cell Treatment. Pharm Res 31, 2904–2917 (2014). https://doi.org/10.1007/s11095-014-1386-3

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  • DOI: https://doi.org/10.1007/s11095-014-1386-3

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