Nanotechnology combined therapy: tyrosine kinase-bound gold nanorod and laser thermal ablation produce a synergistic higher treatment response of renal cell carcinoma in murine model

Authors: LIU, JAMES - TULANE UNIVERSITY; ABSHIRE, CALEB - TULANE SCHOOL OF MEDICINE; CARRY, CONNOR - TULANE SCHOOL OF MEDICINE; SHOLL, ANDREW - TULANE UNIVERSITY; MANDAVA, SREE - TULANE UNIVERSITY; DATTA, AMRITA - TULANE SCHOOL OF MEDICINE; RANJAN, MANISH - TULANE SCHOOL OF MEDICINE; CALLAGHAN, CAMERON - TULANE SCHOOL OF MEDICINE; PERALTA, DONNA; WILLIAMS, KRISTEN - UNIVERSITY OF NEW ORLEANS; LAI, WEIL - TULANE SCHOOL OF MEDICINE; ABDEL-MAGEED, ASIM - TULANE SCHOOL OF MEDICINE; TARR, MATTHEW - UNIVERSITY OF NEW ORLEANS; LEE, BENJAMIN - TULANE UNIVERSITY

Submitted to: BJU International
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/24/2016
Publication Date: 8/17/2016
Citation: Liu, J., Abshire, C., Carry, C., Sholl, A.B., Mandava, S.H., Datta, A., Ranjan, M., Callaghan, C., Peralta, D.V., Williams, K.S., Lai, W.R., Abdel-Mageed, A.B, Tarr, M., Lee, B.R. 2016. Nanotechnology combined therapy: tyrosine kinase-bound gold nanorod and laser thermal ablation produce a synergistic higher treatment response of renal cell carcinoma in murine model. BJU International. 119(2):342-348. https://doi.org/10.1111/bju.13590.
DOI: https://doi.org/10.1111/bju.13590

Interpretive Summary: Tyrosine kinase inhibitors (TKI) and gold nanorods (AuNR) were paired with nanoparticles with photothermal heating in a human metastatic clear cell renal cell carcinoma mouse model. Nanoparticles have been successful as a platform for targeted drug delivery in the treatment of urologic cancers. Likewise, the use of nanoparticles in photothermal tumor heating, though early in its development, has provided promising results. Our previous in vitro studies of nanoparticles loaded with both TKI and AuNR and paired with photothermal ablation have demonstrated significant synergistic cell kill greater than each individual arm alone. This study is a translation of our initial findings to an in vivo model.

Technical Abstract: Immunologically naïve nude mice (Athymic Nude-Foxn1nu) were injected bilaterally on the flanks (n=36) with 2.5 x 106 cells of a human metastatic renal cell carcinoma cell line (RCC 786-O). Subcutaneous xenograft tumors developed 1 cm palpable nodules. AuNR encapsulated in Human Serum Albumin (HSA) Protein nanoparticles were synthesized with or without a TKI and injected directly into the tumor nodule. Irradiation was administered with an 808 nm LED diode laser for six minutes. Animals were sacrificed 14 days post-irradiation; tumors were excised, formalin fixed, paraffin embedded, and evaluated for size and percent necrosis by a GU pathologist. Untreated contralateral flank tumors were used as controls. In mice that did not receive irradiation, TKI alone yielded 4.2% tumor necrosis on the injected side and administration of HSA-AuNR-TKI alone yielded 11.1% necrosis. In laser ablation models, laser ablation alone yielded 62% necrosis and when paired with HSA-AuNR had 63.4% necrosis. The combination of laser irradiation and HSA-AuNR-TKI had cell kill of 100%. In the absence of laser irradiation, TKI treatment alone or when delivered via nanoparticle produced moderate necrosis. Irradiation with and without gold particles alone also improves tumor necrosis. However, when irradiation is paired with gold particle and drug-loaded nanoparticle, the combination therapy demonstrated the most significant and synergistic complete tumor necrosis of 100% (p<0.05). This study illustrates the potential of combination nanotechnology as a new approach in the treatment of urologic cancers.