Synthesis of Porous Au-Shell-Coated Silica Nanoparticles (SiO₂@Au@AuPS) under Mild Conditions for Photothermal Therapy and Chemotherapy of Cancer Cells

Multifunctional nanoparticles (NPs) have gained considerable attention for cancer imaging and treatment. Herein, we develop novel multifunctional nanoprobes called SiO₂@Au@Au porous shells (SiO₂@Au@AuPS). SiO₂@Au is fabricated by introducing 4 nm Au NPs to the thiol-modified SiO₂ surface, after which alloy shells with different Ag/Au ratios are added. Shell modification is then implemented to obtain a porous structure via Ag etching using a dealloying reaction. Among the NPs, SiO₂@Au@AuPS with an Au/Ag ratio of 1.5 (SiO₂@Au@AuPS_1.5) has a well-structured porous Au shell, with a number of nanogaps confirmed by the strongest Raman signal. Furthermore, SiO₂@Au@AuPS decorated with PEG, 4-MBA, and anti-CD44 antibodies shows photothermal conversion effects under 980 nm, with a maximum drug loading capacity of 75.7 μg mg^-1 for doxorubicin (DOX) and a releasing efficiency reaching 53.9% in a pH 6.0 buffer solution within 4 h. In vitro treatment of MDA-MB-231 breast cancer cells with SiO₂@Au@AuPS_1.5@PEG/4-MBA/anti-CD44/DOX decreases the cell viability to 20.3% under near-infrared laser irradiation with successful NP delivery and DOX release. Additionally, in vivo photothermal therapy/chemotherapy with tail-vein-injected SiO₂@Au@AuPS_1.5@PEG/4-MBA/anti-CD44/DOX is effective for cancer cell treatment. Our developed porous nanostructure presents possibilities for synergetic methods of effective photothermal treatment and drug delivery.