Large-capacity DNA vectors based on rolling circle amplification with multivalent aptamers delivery copper sulfide for the synergistic treatment of Cancer through chemo/Photothermal/Chemodynamic therapy in vitro

Developing multifunctional nanomedicines represents a frontier. We have engineered a high-capacity DNA vector basing rolling circle amplification for the delivery of copper sulfide nanoparticles (CuS NPs) and doxorubicin (DOX), coupled with multivalent aptamers (MA) that precisely target tumors, culminating in a multifunctional nanoplatform (RMAL₁Cu@DOX), which combines the chemotherapy (CT)/photothermal therapy (PTT)/chemodynamic therapy (CDT). The vector (RMAL₁) boasts exceptional biocompatibility and incorporates multiple copy units, enabling the precise loading of numerous CuS NPs, forming RMAL₁Cu which possesses a robust photothermal effect and superior Fenton-like catalytic activity, heralding a project of minimally invasive dual-mode (PTT/CDT) therapy. Furthermore, the abundance of G-C of RMAL₁ enabled effective DOX encapsulation through π-π interactions to construct RMAL₁Cu@DOX. The MA integrated into RMAL₁Cu@DOX is pivotal in enhancing the targeting of tumors and in preventing non-specific release of CuS and DOX, enabling an integrated CT/PTT/CDT. Data indicate that 1 nM of RMAL₁Cu could load 270 nM of DOX with an impressive loading capacity of 77 %, and modification with MA, its tumor-targeting ability was amplified by 51-fold and significantly bolstered in vitro imaging outcomes, and the synergistic killing of B16 was as 67.3 %. This innovative nanoplatform offers a comprehensive and holistic strategy for the treatment of malignant tumors.