BSA-Bioinspired Gadolinium Hybrid-Functionalized Hollow Gold Nanoshells for NIRF/PA/CT/MR Quadmodal Diagnostic Imaging-Guided Photothermal/Photodynamic Cancer Therapy.

Multimodal imaging-guided synergistic therapy promises a more accurate diagnosis and higher therapeutic efficiency than single imaging modality or their simple "mechanical" combination. In this research, we have constructed an innovative multifunctional drug delivery platform by gadolinium (Gd)-based bovine serum albumin (BSA) hybrid-coated hollow gold nanoshells (Au@BSA-Gd). The obtained nanoparticles exhibited excellent photothermal effect and computed tomography (CT)/photoacoustic (PA) activity. Besides, the BSA-bioinspired gadolinium complex endowed the nanoparticles with an excellent T1 contrast agent for magnetic resonance imaging (MRI). In addition, the near-infrared (NIR) absorbing phototherapeutic agent [indocyanine green (ICG)] was loaded into the Au@BSA-Gd nanoparticles because of their unique, hollow, and porous structures, thus possessing photodynamic/photothermal property and near-infrared fluorescence (NIRF)/PA imaging capability. As a result, a combined cancer therapy containing the photothermal therapy of Au@BSA-Gd and the synchronous photodynamic/photothermal therapy of ICG was constructed. Furthermore, the well-designed nanocomposites with multiple integrated modalities enabled them to be an ideal nanotheranostic agent for NIRF/PA/CT/MR quadmodal imaging. Therefore, the ICG-loaded albumin-bioinspired gadolinium hybrid-functionalized hollow gold nanoshells (ICG-Au@BSA-Gd) hold great promise as a theranostic platform for simultaneous therapeutic monitoring and precise cancer therapy.