Simultaneous multimodal imaging and photothermal therapy via renal-clearable manganese-doped copper sulfide nanodots

Ultrasmall sized renal clearable nanoparticles are promising nanomaterials for cancer diagnostic and therapeutic treatments owing to their efficient clearance characteristics and feasible therapeutic effects. However, to integrate multifunction and keep ultrasmall size (<6 nm) of the nanoparticles simultaneously is a great challenge for the synthesis of renal clearable nanoparticles. In this manuscript, we engineered an ultrasmall (4.95 nm) triple-modal imaging platform by chelate-free doping of manganese²⁺ (Mn²⁺) and ⁶⁸gallium³⁺ (Ga³⁺) into the matrix of copper sulfide (CuS) nanodots (NDs) using bovine serum albumin (BSA) as the synthetic template. The resulting Mn/⁶⁸Ga-CuS@BSA nanodots proved to be an excellent contrast agent for magnetic resonance (MR), positron emission tomography (PET), and photoacoustic (PAT) imaging. All three imaging modalities confirmed that Mn/Ga-CuS@BSA NDs could be efficiently cleared via the renal-urinary route of intravenous injection, therefore effectively minimized its toxicity to non-tumor organs. In addition, Mn/⁶⁸Ga-CuS@BSA NDs functioned as a potent mediator for the near-infrared (NIR) laser-induced photothermal therapy (PTT), and significantly suppressed tumor growth in the SKOV-3 ovarian tumor model. Our results demonstrated that renal clearable inorganic nanoparticles with multiple imaging and therapeutic capabilities are robust platforms to battle cancer.