Nucleolin-targeted carbon/manganese nanoparticles for synergistic anti-tumor therapy

To address the limitations of single therapy and ensure the safe and efficient delivery of nanomedicine, we developed carbon/manganese nanoparticles (NPs). These NPs were engineered by depositing manganese dioxide on the surface of mesoporous carbon (MMCN), thus enabling Peroxidase (POD)-Catalase (CAT)-Glutathione peroxidase (GPX)-like function. Following the modification with AS1411 aptamer (AMMCN), doxorubicin hydrochloride (DOX) was incorporated to produce AMMCN@DOX. This compound demonstrated satisfactory biocompatibility, efficient tumor tissue accumulation, and the capability to release DOX in response to the tumor microenvironment (TME). It was confirmed that AMMCN@DOX is effectively endocytosed by cells, releases DOX, decomposes H₂O₂ to generate O₂ to alleviate tumor hypoxia, and mediates a Fenton-like reaction. Additionally, AMMCN@DOX showed excellent photothermal conversion efficiency, producing localized heating in tumors and yielding superior synergistic anti-tumor activity in mice with solid tumors. Thus, this study proposes a safe, targeted delivery strategy for carbon/manganese NPs, facilitating chemical, chemokinetic, and photothermal synergistic therapy.