Surface-enhanced Raman scattering (SERS)-active gold nanochains for multiplex detection and photodynamic therapy of cancer.

Multifunctional nanomedicine holds considerable promise as the next generation of medicine that will enable early detection of diseases, as well as simultaneous monitoring and therapy with minimal toxicity. In particular, surface-enhanced Raman scattering (SERS) technology with high sensitivity and multiplexing capabilities is emerging as a powerful alternative for identifying specific biological targets in live cells. In this paper, we present the synthesis of SERS-active gold nanochains (AuNCs) as a potential theranostic system for multiplex detection and photodynamic therapy (PDT) of cancer. AuNCs were prepared by a simple physical mixing method to assemble citrate-stabilized gold nanoparticles into nanochains using hyaluronic acid and hydrocaffeic acid (HA-HCA) conjugates as templates. In addition, Raman reporters and photosensitizers (PSs) were conjugated onto the surface of the AuNCs for multiplex detection and PDT action. After mixing with HA-HCA conjugates, citrate-stabilized gold nanoparticles formed the AuNC structure, and AuNC length was controlled by the HCA conjugation ratio in the HA-HCA conjugates. AuNCs exhibited maximal absorption in the near-infrared (NIR) spectral region and effective SERS property. Confocal microscopy, flow cytometry, Raman spectroscopy and Bio-TEM measurements were used to determine cellular uptake of the Raman reporter, PS and AuNCs in HeLa cells. AuNCs conjugated with Raman reporter and PS (HA-HCAn-Au-Pheo-NPT) showed more than 99% cellular uptake and exhibited excellent phototoxicity even at low PS concentrations compared with free PS after laser irradiation. This SERS-active AuNC (HA-HCAn-Au-Pheo-NPT) shows promise for applications in theranostics, integrating SERS imaging and PDT.