In-situ drug generation and controllable loading: rational design of copper-based nanosystems for chemo-photothermal cancer therapy

Abstract

Chemo-photothermal therapy is a promising combination treatment of cancer owing to the synergistic anticancer effect via different anticancer mechanisms. Nanotheranostics integrating facile preparation and tunable loading of chemotherapeutics and photothermal agents are of great interest owing to the prospect of efficient combinational cancer treatment and large-scale manufacture towards clinical translation. Herein, we present an “in-situ drug generation and controllable loading” strategy to fabricate nanotheranostic agents with such merits and demonstrate the feasibility by the aqueous-phase one-pot synthesis of BSD nanoparticles (NPs), where cancericidal copper diethyldithiocarbamate (Cu(DTC)2) and photothermal copper sulfide (CuS) were in-situ synthesized by the reactions of Cu2+ and corresponding anions (DTC and S2-) in water and efficiently loaded by using bovine serum albumin as a nanocarrier. This design avoids using organic solvents and realizes high loading efficiency of Cu(DTC)2 and CuS, whose composition ratio was dictated by the feeding ratios of DTC/S2-. BSD NPs maintained the excellent photothermal effect, photostability, and photoacoustic imaging capacity of CuS at a high S2-/DTC ratio, while exhibited enhanced photothermal effect at a low ratio of S2-/DTC owing to the formation of Cu(DTC)2-dispersed CuS nanodots. The optimal BSD-1:1 showed a photothermal conversion efficiency of 49.5%, enhanced cellular uptake and cytotoxicity upon laser treatment, and efficient ablation of B16 melanoma tumor by photoacoustic imaging-guided therapy. The facile, tunable nature of this strategy presages that this platform could be expanded to construct diverse, modular metal-based nanosystems for multimodal imaging and therapy.