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TU‐F‐CAMPUS‐T‐03: Enhancing the Tumor Specific Radiosensitization Using Molecular Targeted Gold Nanorods
Author(s) -
Diagaradjane P,
Deorukhkar A,
Sankaranarayanapillai M,
Manohar N,
Singh P,
Goodrich G,
Tailor R,
Cho S,
Krishnan S
Publication year - 2015
Publication title -
medical physics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 180
eISSN - 2473-4209
pISSN - 0094-2405
DOI - 10.1118/1.4925818
Subject(s) - in vivo , biodistribution , internalization , cancer research , epidermal growth factor receptor , in vitro , clonogenic assay , chemistry , cetuximab , materials science , medicine , cancer , cell , receptor , colorectal cancer , biology , biochemistry , microbiology and biotechnology
Purpose: Gold nanoparticle (GNP) mediated radiosensitization has gained significant attention in recent years. However, the widely used passive targeting strategy requires high concentration of GNPs to induce the desired therapeutic effect, thus dampening the enthusiasm for clinical translation. The purpose of this study is to utilize a molecular targeting strategy to minimize the concentration of GNPs injected while simultaneously enhancing the tumor specific radiosensitization for an improved therapeutic outcome. Methods: Cetuximab (antibody specific to the epidermal growth factor receptor that is over‐expressed in tumors) conjugated gold nanorods (cGNRs) was used for the tumor targeting. The binding affinity, internalization, and in vitro radiosensitization were evaluated using dark field microscopy, transmission electron microscopy, and clonogenic cell survival assay, respectively. In vivo biodistribution in tumor (HCT116‐colorectal cancer cells) bearing mice were quantified using inductively coupled plasma mass spectrometry. In vivo radiosensitization potential was tested using 250‐kVp x‐rays and clinically relevant 6‐MV radiation beams. Results: cGNRs displayed excellent cell‐surface binding and internalization (∼31,000 vs 12,000/cell) when compared to unconjugated GNRs (pGNRs). In vitro, the dose enhancement factor at 10% survival (DEF10) was estimated as 1.06 and 1.17, respectively for both 250‐kVp and 6‐MV beams. In vivo biodistribution analysis revealed enhanced uptake of cGNRs in tumor (1.3 µg/g of tumor tissue), which is ∼1000‐fold less than the reported values using passive targeting strategy. Nonetheless, significant radiosensitization was observed in vivo with cGNRs when compared to pGNRs, when irradiated with 250‐kVp (tumor volume doubling time 35 days vs 25 days; p=0.002) and 6 MV (17 days vs 13 days; p=0.0052) beams. Conclusion: The enhanced radiosensitization effect observed with very low intratumoral concentrations of gold and megavoltage x‐rays using the active targeting strategy holds promise for clinical translation of this strategy from a toxicity and cost‐effectiveness perspective and could evolve as a paradigm‐changing approach in the field of radiation oncology.