Cold simulation of one pot in situ synthesis of radioactive gold 198 nanoparticle encapsulated by albumin for application in cancer theranostics

ANDRESSA A DA SILVA; ADRIANA N GERALDES; FREDERICO A GENEZINI; ADEMAR LUGAO; GETHZEMANI M ESTRADA; JANAINA BARROS; MARIANO GRASSELLI; JESSICA LEAL; JORGE GABRIEL S BATISTA; GUSTAVO HENRIQUE C VARCA; KATTESH V KATTI

Montreal

Congreso; 10th World Biomaterial Congress; 2016

WBC 2016 Executive Committee

General Session - Tissue targeting nanoparticles Friday, May 20 | 14:00 - 15:00 | Room: 511E 318.4 Cold simulation of one pot in situ synthesis of radioactive gold 198 nanoparticle encapsulated by albumin for application in cancer theranostics Jessica Leal1, Andressa A Da Silva1, Gethzemani M Estrada1, Jorge Gabriel S Batista1, Adriana N Geraldes1, Janaina Barros1, Gustavo Henrique C Varca1, Frederico A Genezini1, Mariano Grasselli2, Kattesh V Katti3, Ademar Lugao1.1Instituto de Pesquisas Energeticas e Nucleares, Sao Paulo, Brazil; 2National University of Quilmes, Quilmes, Argentina; 3Departments of Radiology, Physics and Chemistry, University of Missouri, Columbia, MO, United States Albumin features set of characteristics that assures applications as natural drug carriers with particular attractive properties in oncology. Albumin may be easily crosslinked and engineered towards loading of large amount of hydrophobic molecules as well as hydrophilic ones[1]. They can be bound in a reversible way and the delivery controlled by endogenous mechanism. Alternatively to conventional systems, albumin can be crosslinked by radiation in such way that dialdehydes or toxic chemicals are totally avoided as shown in the next figure[2[3] {{AbstractFigure.2}} On the other hand, radioactive ions are commonly employed for diagnostic and therapeutic applications. As an example, radioactive gold nanoparticles are currently employed in radiotherapy whether to increase local dose deposition in tissue during radiotherapy or as a local emitter of gamma and beta rays. The radioactive properties of gold include: 198Au (βmax=0.96 MeV; t1/2 = 2.7 days) and 199Au (βmax =0.46 MeV; t1/2 = 3.14 days), making it a strong candidate for theranostics [4] [5]. Conjugation of such materials with sugars, peptides, antibodies, proteins among others is routinely used nowadays for targeting. While radioactive nanoparticles can offer a much higher dose payload than ions for therapy and diagnostic, in addition to the the huge surface to bind targeting species presented by the nanoparticles, functionalization with proteins may potentially increases the particle uptake by tumors or tissues. The main purpose of this work was the development of one pot in situ synthesis of radioactive gold 198 nanoparticle encapsulated by albumin for application in cancer Theranostics. While crosslinked albumin may provide a nontoxic coating on AuNPs with a controllable hydrodynamic diameter, conventional AuNP can be activated by nuclear reactor to produce 198AuNP. The gamma or beta radiation originated from the gold nanoparticle was used to crosslink the Albumin layer. The use of a radioactive particle able to emit radiation for crosslinking of the Albumin layer and simultaneous theranostic application was tried for the first time. The elegant procedure and ease of production combined with the properties of 198Au and the safety of 198AuNP/BSA make this new particle an exciting advancement in cancer therapy and diagnosis. For such purpose, radioactive tetrachloroauric acid H198AuCl4 was produced from gold foils of high purity by neutron irradiation in IPEN research nuclear reactor. 198AuNP/BSA were synthesized by stirring aqueous solutions of BSA and radioactive tetrachloroauric acid H198AuCl4. The reaction mixtures were stirred continuously at 25 °C. The color of the mixture become purple-red from pale yellow within 15 minutes indicating the formation of gold nanoparticles as show in the figure bellow. The reaction mixture was stirred for an additional 20 minutes. The AuNP/BSA formed were characterized by UV-Vis spectrophotometry, DLS and TEM analysis. Gold nanoparticle encapsulated by crosslinked Albumin was prepared in reproducible way. The gold nanoparticle core size measured by TEM was about 20 nm and about 60 to 70 nm with the albumin layer as measured by DLS. Bityrosine formation was measured by fluorescence and it was an evidence of intramolecular and intermolecular crosslinking [6][7]. In conclusion the technique was suitable for the in situ production of the crosslinked albumin functionalized radioactive gold nanoparticles. Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPq) project number 402887/2013-1 and 401438/2014-7. International Atomic Energy Agency (IAEA) CRP code F22064. References: [1] Gustavo H.C. Varca, Gabriela G. Perossi, Mariano Grasselli, Ademar B. Lugão, Radiation synthesized protein-based nanoparticles: A technique overview, Radiation Physics and Chemistry, 2014:105 48? 52. [2] Rodrigo G. Queiroz, Gustavo H.C. Varca, Slawomir Kadlubowski, Piotr Ulanski, Ademar B. Lugão, Radiation-synthesized protein-based drug carriers: Size-controlled BSA nanoparticles, International Journal of Biological Macromolecules, 2016:85 82? 91. [3] Nripen Chanda, Vijaya Kattumuri, Ravi Shukla, Ajit Zambre, Kavita Katti, Anandhi Upendran,Rajesh R. Kulkarni, Para Kan, Genevieve M. Fent, Stan W. Casteel, C. Jeffrey Smith, Evan Boote,J. David Robertson, Cathy Cutler, John R. Lever, Kattesh V. Katti, and Raghuraman Kannan Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity, PNAS 2010 107 (19) 8760-8765; April 21, 2010. [4] Kattumuri, V., Katti, K., Bhaskaran, S., Boote, Evan J., Casteel, Stan W., Fent, Genevieve M., Robertson, David J., Chandrasekhar, M., Kannan, R. and Katti, Kattesh V. (2007), Gum Arabic as a Phytochemical Construct for the Stabilization of Gold Nanoparticles: In Vivo Pharmacokinetics and X-ray-Contrast-Imaging Studies. Small, 3: 333?341. [5] Gustavo H.C. Varca, Rodrigo G. Queiroz, Ademar B. Lugão, Irradiation as an alternative route for protein crosslinking: Cosolvent free BSA nanoparticles, Radiation Physics and Chemistry, 2016. http://dx.doi.org/10.1016/j.radphyschem.2016.01.021. [6] Silvia L. Soto Espinoza, Mirna L. Sánchez, Valeria Risso, Eduardo E. Smolko, Mariano Grasselli, Radiation synthesis of seroalbumin nanoparticles, Radiation Physics and Chemistry, 2012:81 1417?1421. [7] Evelina Miele, Gian P. Spinelli, Ermanno Miele, Federica Tomao, Silverio Tomao, Albumin-bound formulation of paclitaxel (Abraxane® ABI-007) in the treatment of breast cancer, International Journal of Nanomedicine, 2009:4 99?105. Figure 1 Abstract Book - 10th World Biomaterials Congress - Montreal, Canada - May 17-22, 2016 533