468790 Theranostic Multibranched Gold Nanoantennas for Breast Cancer Diagnostics and Therapeutics

Thursday, November 17, 2016: 10:18 AM
Golden Gate 7 (Hilton San Francisco Union Square)
Joseph A. Webb1, Yu-Chuan Ou1, Shannon L. Faley2, Christine M. O'Brien3, Isaac J. Pence3, Maryse Lapierre-Landry3, Melissa C. Skala3, Anita Mahadevan-Jansen3, Leon M. Bellan2 and Rizia Bardhan1, (1)Chemical Engineering, Vanderbilt University, Nashville, TN, (2)Mechanical Engineering, Vanderbilt University, Nashville, TN, (3)Biomedical Engineering, Vanderbilt University, Nashville, TN

Breast cancer is one of the leading causes of non-communicable disease death in women worldwide. Especially dangerous and lethal are the breast cancers that have genetic mutations for surface receptors utilized in drug therapy. Specifically, breast cancer cells triple negative for the progesterone, estrogen, and Her2/neu receptors are impervious to most therapies and can even become resistant to some chemotherapy drugs. This resistance calls for new and innovative treatments that be optimized for cancers based on an individual patient basis/cancer phenotype.

Nanoparticle based diagnostics and therapeutics have recently emerged as a novel platform for management and mitigation of cancer at all stages. Gold nanostructures, specifically, have multiple characteristics that make them ideal for cancer theranostics including high biocompatibility, ease of bioconjugation, ability to tune their plasmon resonance to absorb tissue penetrating near infrared light, their use as contrast agents, and ability to convert light to heat when excited at the plasmon resonance for photothermal ablation of cancer cells. In this work we demonstrate the use of near-infrared light absorbing multibranched gold nanoantennas (MGNs) to simultaneously deliver diagnostic and therapeutic (theranostic) capabilities in triple negative breast cancer cells (MDA MB 231). MGNs consist of a core that absorbs light and protrusions that serve as emitters confining light into a localized area generating enhanced local fields via the nanoantenna effect and intense photothermal response. By exploiting these optical properties of MGNs we have utilized them for ultrasensitive surface enhanced Raman scattering (SERS) imaging to visualize MDA MB 231 cells with single-cell resolution in vitro and subsequently performed photothermal therapy to enable cell death using low laser powers of < 5W/cm2.

By synthesizing various Raman reporter/receptor target combinations, multiplex imaging can be achieved, providing a cellular “traffic map” demonstrating receptor expression in vitro. Further, due to the narrow peak width fundamental to Raman spectroscopy, these multiple tags can be distinguished in vivo, even while amidst the many signals within tissue. We confirmed the feasibility of theranostic MGNs in vivo as multiplexing agents by observing the SERS signal over a longitudinal study and determined the max accumulation within human cancer xenografts. Lastly, these MGNs were utilized as contrast agents for photothermal optical coherence tomography (PTOCT) combining the high sensitivity of SERS and the high resolution and high tissue penetration depths of PTOCT within a single nanoagent to perform dual modal imaging.

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