Gold Nanoframeworks with Mesopores for Raman–Photoacoustic Imaging and Photo‐Chemo Tumor Therapy in the Second Near‐Infrared Biowindow

Gold-based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near-infrared (NIR-II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR-II gold nanostructures, a particular liposome template-guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR-II region, affording their capacity of NIR-II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44-overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4-aminothiophenol (4-ATP) onto AuNFs yields a surface-enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA-4-ATP-AuNFs-DOX on tumor-bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR-II under PA-Raman dual image-guided photo-chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.