Ms. Safra Rudnick-Glick Profile

Safra Rudnick-Glick

at Bar-Ilan Univ

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Proceedings Article | 21 August 2015 Presentation + Paper

Biodegradable bisphosphonate nanoparticles for imaging and therapeutic applications in osteosarcoma

S. Rudnick-Glick, E. Corem-Salkmon, I. Grinberg, E. Gluz, S. Margel

Proceedings Volume 9550, 955004 (2015) https://doi.org/10.1117/12.2186765

KEYWORDS: Bone, Nanoparticles, Tumors, Near infrared, Luminescence, Content addressable memory, Magnesium, Toxicity, Blood, In vivo imaging

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Osteosarcoma (OS) is amongst the most commonly diagnosed bone tumors occurring in adolescence, young adults and adults over the age of 65. Current treatment is based on a combination of surgery and chemotherapy. Chemotherapy has improved the survival rate, however it is associated with severe side effects due to the use of high dosages, nonspecific uptake and poor bone blood supply. At present bisphosphonates (BP) are widely used in the treatment of bone disorders including OS. We have engineered a unique biodegradable BP nanoparticle that possesses a dual functionality: 1) covalent attachment of a dye (e.g., NIR dye) or drug to the nanoparticles through the primary amine groups on the surface of the nanoparticle; 2) chelation to the bone mineral hydroxyapatite through the BP on the surface of the nanoparticle. Due to a high concentration of PEG in the BP nanoparticles they possess a relatively long plasma half-life time. Therefore, the nanoparticle has potential for use both in diagnosis and therapy of OS. Doxorubicin was conjugated to the free amine on the surface of the BP nanoparticles. In vitro experiments on osteosarcoma cells demonstrated that the doxorubicin-conjugated BP nanoparticles possess a higher efficacy than the free doxorubicin. Further investigation in vivo in a chicken embryo model confirmed that the doxorubicin-conjugated nanoparticle was significantly more effective in inhibiting tumor growth compared to free doxorubicin at a similar concentration. Additionally, we have shown that these BP nanoparticles preferentially target OS tumor tissue, thus increasing anti-cancer drug bioavailability at targeted site.

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