Renal-clearable luminescent gold nanoparticles incorporating active and bio-orthogonal tumor-targeting for drug delivery and controlled release

The use of ultrasmall gold nanoparticles (AuNPs) as drug delivery systems (DDSs) represents certain challenges, including limited targeting efficiency, uncontrolled drug release, and off-target drug toxicity. Herein, we synthesize a series of second near-infrared (NIR-II) region emitting AuNPs by incorporating both c(RGDfC) peptide and cucurbit[7]uril (CB[7]) for active and bio-orthogonal tumor-targeting, respectively. The CB[7]/c(RGDfC)-AuNPs exhibited rapid tumor accumulation and prolonged retention, which were utilized as nanocarriers to load oxaliplatin (OX) to afford OX@CB[7]/c(RGDfC)-AuNPs for targeted drug delivery and tumor chemotherapy. The mice treated with OX@CB[7]/c(RGDfC)-AuNPs achieved superior therapeutic outcomes compared to three times the dose of OX treatment (H-OX group). Meanwhile, the AuNPs showed excellent biosafety as opposed to obvious hepatotoxicity and severe hepatorenal toxicity observed in the mice treated with low dose of OX and H-OX, respectively. This renal-clearable DDS holds promise for precise drug delivery and controlled release, offering new perspectives and methods for clinical cancer treatment.