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Posted: Sep 29, 2010

The advantages of using functionalized fullerenes for cancer imaging and therapy

(Nanowerk Spotlight) Gold-based nanostructures (e.g., nanoshells and nanorods) and carbon nanotubes have been successfully applied for photoacoustic imaging (example) and photothermal treatment (example) of tumors. Medical researchers believe that such nanoparticle-mediated, image-guided cancer therapy has tremendous promise for increasing the efficacy of cancer treatment while reducing toxic side effects traditionally associated with treatment.
Working with a different carbon nanomaterial, researchers at the University of Florida, led by Stephen Grobmyer, Ben Koopman and Brij Moudgil, now have been first to show that polyhydroxy fullerenes can be utilized for the same purposes. The minute size and biocompatibility of polyhydroxy fullerenes make them particularly attractive for biomedical applications.
"Limited solvent compatibility, non-biodegradability and concerns over the safety of various nanomaterials may hinder their commercialization," Vijay Krishna tells Nanowerk. "In our new work, we show that the photothermal and photoacoustic properties of polyhydroxy fullerenes (PHF) – which are water-soluble, biodegradable, antioxidant, and rapidly excreted – can be applied for imaging and therapy of cancer."
Krishna, a post doctoral associate at the Particle Engineering Research Center at the University of Florida, Gainesville, is first author of a paper published in the September 3, 2010 online edition of Small ("Polyhydroxy Fullerenes for Non-Invasive Cancer Imaging and Therapy").
In a previous Nanowerk Spotlight earlier this year, we have reported about his group's discovery of novel optical properties of functionalized fullerenes (New fullerene discovery sparks research into medical and industrial applications). In this new work, the researchers present a new, safer alternative for photothermal treatment of tumors based on functionalized fullerenes.
Photoacoustic images of mice tumor before and after intratumoral injection of polyhydroxy fullerenes
Photoacoustic images of mice tumor before (left) and after (right) intratumoral injection of polyhydroxy fullerenes. A large increase in photoacoustic contrast is observed at the site of tumor following injection of polyhydroxy fullerenes. (Image: Dr. Krishna, University of Florida, Gainesville)
Gold-based nanostructures are not biodegradable and are known to accumulate in the liver and spleen, with unknown long-term consequences. Polyhydroxy fullerenes have similar photothermal and photoacoustic properties but they are biocompatible and are rapidly excreted.
"One problem we had to overcome is that PHF are water-soluble and therefore can migrate from the desired location in biological systems" according to Krishna. "In order to overcome this limitation, we designed PHF-containing nanoparticles. Specifically, we explored two nanoparticle matrices – chitosan and silica."
The team either coated their fullerenes on or encapsulated them within fluorescein-doped silica nanoparticles. Alternately, they encapsulated them in biodegradable chitosan at a weight percentage of 0.25 wt% (CP-0.25).
Photoacoustic imaging experiments were then conducted by injecting tumors in mice with the PHF or PHF-containing nanoparticles.
"Both PHF and CP-0.25 provided excellent photoacoustic contrast between the tumor and surrounding non-tumoral tissue" says Krishna. Furthermore, the chitosan matrix of CP-0.25 is biodegradable and amenable for conjugation with targeting ligands.
With regard to therapeutic efficacy, the researchers found that tumors injected with PHF containing nanoparticles (CP-0.25) and exposed to near infrared laser decreased in cross-sectional area by up to 72% within two hours of treatment.
Krishna notes that the rapid reduction in tumor size – two hours versus days in the case of gold based nanostructures – cannot be explained solely by photothermal ablation. "The 'acoustic-explosion' mechanism reported for single-wall carbon nanotubes may better explain the rapid tumor shrinkage" (see: "Cancer-Cell Targeting and Photoacoustic Therapy Using Carbon Nanotubes as 'Bomb' Agents")
As the researchers point out, the use of polyhydroxy fullerenes for cancer theranostics has several advantages over currently proposed single-wall carbon nanotubes and gold based nanostructures: "PHF is water-soluble, biocompatible and biodegradable, and has been shown to possess antioxidant properties, inhibit allergic response and protect tissues of the central nervous system. Furthermore, PHF has been shown to inhibit tumor growth and up-regulate immune system. PHF molecules are 1.3 nm in size and can be easily excreted in urine, whereas larger nanostructures such as carbon nanotubes and gold-based nanostructures typically exceed the renal excretion limit of 5.5 nm."
One of the primary challenges for using PHF in practical applications is to modify the polyhydroxy fullerene molecules so that they will bind with cancer cells, enabling targeted delivery of the polyhydroxy fullerenes to early-stage cancers, which can then be easily located and destroyed.
Another future direction of this research is the study of the long-term biodistribution and clearance of polyhydroxy fullerenes in relevant models to assure their biocompatibility and safety.
"Finally, we must understand the impact of functionalized fullerenes on tumor biology and progression" says says co-team leader Dr. Stephen Grobmyer. "We have recently received funding from U.S. Department of Defense and The Margaret Q. Landenberger foundation for developing biocompatible, multimodal theranostic agents based on polyhydroxy fullerenes."
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