Biomodal Tumor-Targeted and Redox-Responsive Bi2Se3 Hollow Nanocubes for MSOT/CT Imaging Guided Synergistic Low-Temperature Photothermal Radiotherapy

Hyperthemia (>50 degrees C) induced heating damage of nearby normal organs and inflammatory diseases are the main challenges for photothermal therapy (PTT) of cancers. To overcome this limitation, a redox-responsive biomodal tumor-targeted nanoplatform is synthesized, which can achieve multispectral optoacoustic tomography/X-ray computed tomography imaging-guided low-temperature photothermal-radio combined therapy (PTT RT). In this study, Bi2Se3 hollow nanocubes (HNCs) are first fabricated based on a mild cation exchange way and Kirkendall effect and then modified with hyaluronic acid (HA) through redox-cleavable linkage (-s-s-), thus enabling the HNC to target cancer cells overexpressing CD-44 and control the cargo release profile. Finally, gambogic acid (GA), a type of heat-shock protein (HSP) inhibitor, which is vital to cells resisting heating-caused damage is loaded, into Bi2Se3 HNC. Such HNC-s-s-HA/GA under a mild NIR laser irradiation can induce efficient cancer cell apoptosis, achieving PTT under relatively low temperature (approximate to 43 degrees C) with remarkable cancer cell damage efficiency. Furthermore, enhanced radiotherapy (RT) can also be experienced without depth limitation based on RT sensitizer Bi2Se3 HNC. This research designs a facile way to synthesize Bi2Se3 HNC-s-s-HA/GA possessing theranostic functionality and cancer cells-specific GSH, but also shows a low-temperature PTT RT method to cure tumors in a minimally invasive and highly efficient way.