Gold nanocluster-loaded hybrid albumin nanoparticles with fluorescence-based optical visualization and photothermal conversion for tumor detection/ablation.

Gold nanoclusters (AuNCs) are viewed as effective hyperthermal agents for the treatment of tumors. Whereas AuNCs formed by the agglomeration of several to tens of gold atoms (<1-2 nm) possess significant fluorescence, they have a negligible hyperthermal effect, while AuNCs comprised of spherical gold nanoparticles (AuNPs > a few nanometers) have a marked hyperthermic effect but lose their inherent fluorescence and obstruct the intensity of neighboring fluorescent dyes due to Forster resonance energy transfer (FRET). To achieve both hyperthermia and fluorescence-based optical visualization, we generated hybrid albumin nanoparticles containing AuNCs (~88 nm) comprising AuNPs (~4.5 nm). We generated a series of formulated AuNCs and optimized the size, morphology, NIR absorbance (600-900 nm), hyperthermal activity, and fluorescence spectral characters of the resulting hybrid albumin nanoparticles (AuNCs/BSA-NPs) by considering the interparticle distance between the AuNPs and Cy5.5. Among these, AuNCs/BSA-NPs (formula D) had a strong hyperthermic effect and had well-preserved fluorescence intensity (from the attached Cy5.5) due to localized surface plasmon resonance (LSPR) and a reduction in FRET. These AuNCs/BSA-NPs were able to elevate the surface tumor temperature of HCT116-bearing mice to >50 °C following 808 nm laser irradiation (1.5 W/cm2, 10 min), which remarkably suppressed tumor growth (17.8 ± 16.9 mm3vs. PBS and AuNCs/BSA-NPs (formula E): ~1850 and ~1250 mm3, respectively). Also, Cy5.5-modified AuNCs/BSA-NPs (formula D) showed good performance in optical fluorescence imaging of target tumors in HCT116 tumor-bearing mice. Together, our results indicate that the interparticle distance between albumin or Cy5.5 and AuNPs/AuNCs can be optimized to achieve both hyperthermia and fluorescence emission by striking a balance between LSPR and FRET effects. We believe that the AuNC/BSA-NPs formulation presented here can serve as a potential platform for both optically visualizing and treating colon cancers.