RESUMO
The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin-based carbon dots (Chl-D CDs) are successfully synthesized. Chl-D CDs exhibit unique spectroscopic traits and are found to induce a Fenton-like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl-D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl-D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl-D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl-D CDs' anticancer activity. Notably, the Chl-D CDs' capacity to trigger a Fenton-like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl-CDs can lead to a secure and efficient combined cancer therapy.
Assuntos
Carbono , Clorofilídeos , Ferroptose , Carbono/química , Humanos , Ferroptose/efeitos dos fármacos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Ferro/química , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/química , Apoptose/efeitos dos fármacosRESUMO
Carbon Dots (CDs) have recently attracted a considerable amount of attention thanks to their well-documented biocompatibility, tunable photoluminescence, and excellent water solubility. However, CDs need further analysis before their potential use in clinical trials. Previously, we reported a new type of carbon nitride dot (CND) that displayed selective cancer uptake traits attributed to structural resemblances between CNDs and glutamine. Here, the effects of surface structural differences on the cellular uptake of CNDs are further investigated to understand their selective cancer cell uptake trend. Beyond enhanced drug loading on modified CNDs, our cytotoxicity, western blotting and bioimaging studies proposed that modified CNDs' cellular uptake mechanism is thoroughly linked with ASCT2 and LAT1 transporters. Therefore, CNDs have a promising trait of selective cancer cell targeting by utilizing highly expressed transporters on cancer cells. Additionally, drug loaded CNDs exhibited improved anti-cancer efficacies towards cancer cells along with good non-tumor biocompatibilities.