Au-CuS Hierarchical Self-Assembled Multimodal Diagnosis and Treatment Platform for the Synergistic Treatment of Melanoma.

With the rapid development of nontraditional tumor treatment methods, a variety of nanosystems have been successfully developed. Here, a hierarchical self-assembled multimodal diagnosis and treatment platform was designed based on DNA for targeted imaging and treatment of melanoma (B16). First, gold nanorods (AuNRs) and copper sulfide nanoparticles (CuS NPs) were prepared by the seedless growth method and hydrothermal synthesis method, respectively. Subsequently, AuNRs modified with single-stranded thiol DNA (DNA1-SH) were used as the core (AuNRs-D1) and combined with CuS NPs modified with complementary single-stranded DNA (DNA2-SH) through hydrogen-bonding interactions (CuS-D1), successfully constructing a hierarchical self-assembled composite nanoparticle (AuNRs-D12-CuS). To further enhance the targeting ability of AuNRs-D12-CuS, we modified the surface with the AS1411 aptamer to achieve specific recognition of overexpressed nucleolin on the surface of B16. In addition, doxorubicin (DOX) was effectively incorporated into the AuNRs-D12-CuS, forming a multifunctional nanosystem with chemotherapeutic function (AuNRs-D12-CuS@DOX), and its drug encapsulation efficiency reached approximately 64%. This nanosystem not only possessed the photothermal properties and Fenton-like reaction characteristics of AuNRs and CuS NPs but also had the chemotherapeutic efficacy of DOX, thus achieving the synergistic effect of chemotherapy/photothermal/chemodynamic therapy (CT/PTT/CDT). In vitro experimental results showed that after labeling the prepared composite nanomaterials with nucleic acid red dye (NA-red), the material exhibited excellent fluorescence imaging performance when coincubated with cells for 30 min. In addition, under low-dose conditions, its killing efficiency against B16 cells could reach 50%, which was significantly superior to single-drug treatment or simple photothermal therapy.