Abstract 382: In-vivo imaging of lung cancer using tumor homing peptide coated nanoparticles
Authors: Patel Apurva R. , Lim Ed , Zhang Ning , Francis Kevin , Safe Stephen , Sachdeva Mandip 
Published: August 2012

Purpose: Lung cancer is one of the leading cause of death (1.3 million deaths annually) worldwide and non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers. Vascular endothelial growth factor (VEGF) over-expression (61% to 92% of NSCLC) is associated with poor survival. Recently, new approaches in the treatment of lung cancer with novel drugs that selectively inhibit tumor blood supply thus controlling cancer cell survival, proliferation and/or metastasis in combination with conventional anticancer or antiangiogenic drugs have generated clinical interest, e.g. DIM-C-pPhC6H5 (DIM-P); a c-substituted diindolylmethanes which is novel anti-cancer agent. Objective of this study are: 1) to formulate tumor homing pegylated CREKA peptide coated nanoparticle of DIM-P (PCNCs-D)/ D-luciferin (PCNCs-DL)/ XenolightDiR (PCNCs-Di), 2) In-vivo imaging of tumor progression / tumor vasculature and tracking of PCNCs-Di. Methods: Nanoparticles were prepared with DIM-P (NCs-D)/ D-luciferin (NCs-DL)/XenolightDiR(NCs-Di), Compritol, Miglyol, DOGS-NTA-Ni and sodium taurocholate using high pressure homogenizer (Nano-DeBEE). PCNCs-D and PCNCs-DL/PCNCs-Di were prepared by conjugating NCs-D and NCs-DL/ NCs-Di with 6His-PEG2K-CREKA peptide and characterized for physical properties, clot binding assay and tube formation assay. Pharmacokinetic parameters of formulations were evaluated in BALB/c mice. In-vivo imaging of tumor and tracking of nanoparticles was carried out with IVIS® Spectrum CT (Caliper life Sciences) by using fluorescent dye (Xenolight DIR) and bioluminescence (luciferin) following intravenous and inhalation delivery of nanoparticles. Results: Particle size of PCNCs-D was 190-210 nm. The PCNCs-D formulation showed an initial burst release followed by a slow release up to 72 hr (90%) of DIM-P. PCNCs-D showed (p&lt;0.001) 3 fold higher binding to the clotted plasma proteins compared to NCs-D. PCNCs-D decreased average branching point by 68 ± 5 percent compared to 39 ± 4 percent by DIM-P alone in a tube formation assay suggesting anti-angiogenic activity. Pharmacokinetic parameters showed that PCNCs-D increased plasma half life of DIM-P from 0.83 ± 0.26 hr to 2.34 ± 0.39 hr. In-vivo imaging following exposure of PCNCs-DL/PCNCs-Di demonstrated their targeting to the tumor vasculature, where the PCNCs-Di were found to migrate more in newly formed blood vessels and total radiant efficiency [p/s] / [µW/cm*2] was 2.1*1012 ± 0.5*1012 over the period of 0.5 hr to 3hr. NCs-Di didn't show any specific migration to tumor vasculature confirming the specific targeting of PCNCs-Di and total radiant efficiency [p/s] / [µW/cm*2] was 0.6*1012 ± 0.18*1012. Conclusion: The results emanating from these studies demonstrate an anti-angiogenic potential of DIM-P and the role of PCNCs-D as an effective tumor homing drug delivery systems for lung cancer treatment.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 382. doi:1538-7445.AM2012-382