Luminescent gold nanocluster-decorated polymeric hybrid particles for laser guided therapy

Gold nanoclusters or ultrasmall gold atom clusters (AuNCs, <2 nm in diameter) exhibit emergent photonic properties in the near-infrared (NIR) spectrum due to the quantization of their conduction band. This gives rise to attractive NIR luminescent properties that offer great promises for imaging and diagnostic purposes in biomedical applications. AuNCs also absorb NIR light in the biological window inducing photothermal events that can facilitate localized drug release and synergistic thermal therapy. Here, we designed a micellar system based on poly(ethylene glycol) (PEG) and thermosensitive poly(N-isopropylacrylamide) (PNIPAM) copolymerized with functional monomers to allow for micellar core-crosslinking via oxo-ester mediated native chemical ligation (OMNCL). These micelles are decorated with AuNCs (<2 nm) and covalently bound thiolated doxorubicin, which allow for both precise intracellular imaging as well as light-induced cell killing. The polymer bound AuNCs exhibit a NIR luminescent emission maximum at ~ 720 nm with a quantum yield of ~ 3%. Internalization studies of the micellar system on MDA-MB-231 cancer cells showed that doxorubicin remains bound within the micelles in the cytosolic region after 24 h incubation. Upon NIR light irradiation at 650 nm, highly localized cell death is observed, which is limited only to the irradiated area. This innovative hybrid material design of the the AuNC-decorated micelles enables an efficient combination of live imaging and precisely controlled therapy.