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

Morrison, Rachel R.; Gardiner, Chris; Evidente, Antonio; Kiss, Róbert; Townley, Helen E.

doi:10.1007/s11095-014-1386-3

Cited by 19 publications

(27 citation statements)

References 39 publications

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“…However, a detailed investigation of its anticancer activity was described only recently [29,31,32]. When tested on eight cancer cell lines at concentrations of less than 1 µM, ophiobolin A inhibited cancer cell growth by 50% after 3 days of culture irrespective of whether the cells displayed a multidrug resistance (MDR) phenotype or were resistant to pro-apoptotic stimuli [29].…”

Section: Introductionmentioning

confidence: 99%

“…In another recent development, ophiobolin A was investigated as a potential treatment of rhabdomyosarcoma (RD), the most common soft tissue sarcoma in children, through its incorporation into chemoembolization particles [32]. The multimodal chemoembolization particles were generated by inserting mesoporous silica nanoparticles, prepared by the sol-gel method, onto the surface of polystyrene microspheres, obtained by suspension copolymerization.…”

Section: Introductionmentioning

confidence: 99%

“…The multimodal chemoembolization particles were generated by inserting mesoporous silica nanoparticles, prepared by the sol-gel method, onto the surface of polystyrene microspheres, obtained by suspension copolymerization. The chemoembolization particles were subsequently loaded with ophiobolin A and demonstrated to exhibit good efficacy against RD cells in culture [32]. …”

Section: Introductionmentioning

confidence: 99%

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Sesterterpenoids with Anticancer Activity

Evidente¹,

Kornienko²,

Lefranc³

et al. 2015

CMC

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Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sesterterpenoids with Anticancer Activity

Evidente¹,

Kornienko²,

Lefranc³

et al. 2015

CMC

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“…The microparticles can also incorporate imaging agents such as fluorophores or heavy metals such as tantalum as X-ray contrast agents (non-magnetic so allows patient to undergo MRI) or combination with chemoembolization (a mixture of mesoporous silica NPs and titania NPs). 8,12 …”

Section: Resultsmentioning

confidence: 99%

Efficacy of radiosensitizing doped titania nanoparticles under hypoxia and preparation of an embolic microparticle

Morrison¹,

Rybak-Smith²,

Thompson

et al. 2017

IJN

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The aim of this study was to develop a manufacturing protocol for large-scale production of doped titania radiosensitizing nanoparticles (NPs) to establish their activity under hypoxia and to produce a multimodal radiosensitizing embolic particle for cancer treatment. We have previously shown that radiosensitizing NPs can be synthesized from titania doped with rare earth elements, especially gadolinium. To translate this technology to the clinic, a crucial step is to find a suitable, scalable, high-throughput method. Herein, we have described the use of flame spray pyrolysis (FSP) to generate NPs from titanium and gadolinium precursors to produce titania NPs doped with 5 at% gadolinium. The NPs were fully characterized, and their capacity to act as radiosensitizers was confirmed by clonogenic assays. The integrity of the NPs in vitro was also ascertained due to the potentially adverse effects of free gadolinium in the body. The activity of the NPs was then studied under hypoxia since this is often a barrier to effective radiotherapy. In vitro radiosensitization experiments were performed with both the hypoxia mimetics deferoxamine and cobalt chloride and also under true hypoxia (oxygen concentration of 0.2%). It was shown that the radiosensitizing NPs were able to cause a significant increase in cell death even after irradiation under hypoxic conditions such as those found in tumors. Subsequently, the synthesized NPs were used to modify polystyrene embolization microparticles. The NPs were sintered to the surface of the microparticles by heating at 230°C for 15 minutes. This resulted in a good coverage of the surface and to generate embolization particles that were shown to be radiosensitizing. Such multimodal particles could therefore result in occlusion of the tumor blood vessels in conjunction with localized reactive oxygen species generation, even under hypoxic conditions such as those found in the center of tumors.

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“…We have previously shown that polystyrene embolic particles can be surface modified with mesoporous silica nanoparticles and loaded with a chemotherapy agent [3]. By adding a drug to an embolic agent, an increased local dose can be administered to a tumour whilst simultaneously reducing harmful systemic effects [4].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of polystyrene embolization particles doped with tantalum oxide nanoparticles for X-ray contrast

Morrison

Thompson

Bird

et al. 2015

J Mater Sci: Mater Med

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Radiopaque and fluorescent embolic particles have been synthesized and characterised to match the size of vasculature found in tumours to ensure effective occlusion of the vessels. A literature search showed that the majority of vessels surrounding a tumour were less than 50 µm and therefore polydispersed polystyrene particles with a peak size of 50 µm have been synthesised. The embolic particles contain 5-8 nm amorphous tantalum oxide nanoparticles which provide X-ray contrast. Embolic particles containing up to 9.4 wt% tantalum oxide were prepared and showed significant contrast compared to the undoped polystyrene particles. The X-ray contrast of the embolic particles was shown to be linear (R(2) = 0.9) with respect to the concentration of incorporated tantalum nanoparticles. A model was developed which showed that seventy-five 50 µm embolic particles containing 10% tantalum oxide could provide the same contrast as 5 cm of bone. Therefore, the synthesized particles would provide sufficient X-ray contrast to enable visualisation within a tumour.

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

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

Cited by 19 publications

References 39 publications

Sesterterpenoids with Anticancer Activity

Sesterterpenoids with Anticancer Activity

Efficacy of radiosensitizing doped titania nanoparticles under hypoxia and preparation of an embolic microparticle

Synthesis and characterization of polystyrene embolization particles doped with tantalum oxide nanoparticles for X-ray contrast

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