Targeted Photodynamic Therapy Activities of Surface-Enhanced Raman Scattering-Active Theranostic System Based on Folate/Hyaluronic Acid-Functionalized Gold Nanochains.

Light-based diagnostics and therapies have become indispensable tools in the field of cancer medicine. Nanotheranostics, namely the integration of diagnostic elements with therapeutic agents into a single nanosized-regimen, have been the recent focus of intense exploration with the aim to develop more specific, individualized therapies and to combine diagnostics and therapeutic capabilities into a single agent. In this study, gold nanochains (AuNCs) with worm-like nanostructures were developed as a light-triggered theranostic system for effective multiplex detection and photodynamic therapy (PDT). We fabricated the AuNC system through assembling of citrate-stabilized gold nanoparticles using hyaluronic acid-hydrocaffeic acid (HA-HCA) conjugates as templates. Raman reporters, photosensitizers (PSs), and active tumor targeting ligands were also conjugated onto the surfaces of the AuNCs. The length of the AuNCs could be controlled by the HCA composition ratio in the HA-HCA conjugates. The AuNCs with worm-like nanostructures exhibited significant surface-enhanced Raman scattering (SERS) properties, and their optical properties depended on their length. The AuNCs conjugated with a Raman reporter, PS, and active targeting ligand (HA-HCA-Au-NPT-FA-Ce6) exhibited excellent selectivity and showed marked phototoxicity even at low concentration of PS compared with free PS after laser irradiation. This tumor-targeting HA-HCA-Au-NPT-FA-Ce6 AuNC system could be a promising approach for applications in cancer theranostics, integrating SERS detection, fluorescence imaging, and PDT.