Theranostic Multibranched Gold Nanoantennas for Cancer Diagnostics via Surface Enhanced Raman Spectroscopy and Photothermal Therapeutics

Abstract

Cancer is the second leading cause of death globally according to the World Health Organization. Aggressive cancers that have genetic mutations for surface receptors require more versatile and multifunctional treatments. Plasmonic nanostructures have emerged as novel platforms for the management and mitigation of cancer due to their high biocompatibility, ease of bioconjugation, tunability of resonance to tissue penetrating wavelengths, and ability to convert light to heat for photothermal ablation. In this work, we synthesized multibranched gold nanoantennas (MGNs) via HEPES-mediated growth method and investigated their performance in delivering simultaneous diagnostic and therapeutic (theranostic) components in cancer models. Due to the presence of multiple sharp protrusions, MGNs demonstrated a refractive index sensitivity of 373 nm/RIU, as well as, intense photothermal efficiencies, rising the temperature of surrounding medium to ~54 °C within 5 minutes of laser illumination. Additionally, MGN-substrates were manufactured for point of care diagnostic (POCD) systems utilizing surface enhanced Raman spectroscopy (SERS). MGN-paper was used to obtain a detection limit of 100 fM of human serum albumin (HSA) complexed with indocyanine green (ICG). Further, by incorporating protein detection via SERS tag technology, we designed a sandwich architecture using MGN-glass for prostate specific antigen (PSA) biomarker sensing. Lastly, we showed the theranostic capability of MGNs in triple negative breast cancer (TNBC) both in vitro and in vivo via human xenografts. Utilizing the light to heat conversion capacities of the MGNs, actively targeted photothermal therapy was demonstrated in EGFR overexpressing MDA MB 231 cells, with no observable off-site toxicities. Lastly, using SERS imaging, we targeted the epidermal growth factor receptor (EGFR) and immune checkpoint receptor, programmed death ligand 1 (PD-L1), and acquired 2-dimensional SERS “traffic maps” of the 231 cells. In addition, a blocking study in vivo revealed ~30 % decrease in SERS signal when receptor sites were occupied, verifying the active targeting properties of the antibody coated MGNs. This encompassed work demonstrates the adaptable potential of the synthesized theranostic MGNs to provide predictive, personalized, and image-guided therapies, facilitating the transition to individualized cancer medicine.