Three dimensional plasmonic assemblies of AuNPs with an overall size of sub-200 nm for chemo-photothermal synergistic therapy of breast cancer

Three dimensional plasmonic assemblies of gold nanoparticles (AuNPs) (gold 3D-PAs) have been recently developed for photothermal therapy, Raman imaging, photoacoustic imaging or X-ray computed tomography imaging because they can generate an enhanced electromagnetic field between the gaps of neighboring AuNPs and significantly improve the localized surface plasmon resonance (LSPR) effect in the near-infrared (NIR) region. However, the sizes of most reported gold 3D-PAs are too large (>300 nm) for in vivo applications as cancer theranostic agents because a size of about 200 nm is often considered to be the upper limit for successful drug delivery based on the enhanced permeation and retention (EPR) effect. Herein, we propose a novel strategy to fabricate the gold 3D-PAs with an overall size of sub-200 nm, whose self-assembly process was verified by TEM, DLS and UV-vis spectroscopy. The cell experiments demonstrate that our gold 3D-PAs allow combined chemotherapy and photothermal therapy. The histopathology assessments indicate that the toxicity of our gold 3D-PAs to normal tissues (side effect) is negligible. The animal experiments indicate that our gold 3D-PAs have a weak chemotherapeutic efficacy without NIR laser irradiation at a low DOX dosage, but shows an excellent therapeutic effect with NIR laser irradiation at the same DOX dosage due to the synergy of chemo-photothermal therapy.