Nicotinamide-derived tumor-targeting carbon dots for Cancer Photothermal therapy.
NAM-derived carbon dots show promise for targeted cancer photothermal therapy by exploiting Ki67 affinity, achieving complete tumor regression in preclinical models.
Where it sits
this study against the rest of the nad+ (nicotinamide adenine dinucleotide) corpusSummary and findings
The study investigated nicotinamide-derived carbon dots (NAM-CDs) for targeted photothermal therapy in cancer. NAM-CDs showed enhanced binding to Ki67, a tumor marker, and demonstrated effective tumor ablation in vivo. Complete tumor regression was observed over a 30-day period following laser irradiation.
Abstract
The lack of tumor-specific targeting remains a major bottleneck in photothermal therapy. Here, we exploit the natural affinity of nicotinamide (NAM) for Ki67, a tumor proliferation marker, to design a targeted photothermal nanomaterial. NAM-derived carbon dots (NAM-CDs) were synthesized via a one-step solvothermal method, in which the carbon core serves as a scaffold for the multivalent presentation of NAM moieties. Dynamic molecular docking simulations revealed that NAM-CDs exhibited a markedly enhanced binding affinity toward Ki67, with binding energy of -7.7 kcal/molcompared with -3.8 kcal/mol for free NAM. These results indicate that the multivalent display of NAM not only preserves but also amplifies its intrinsic Ki67-targeting capability. To further optimize the photophysical properties of NAM-CDs, the synthesis temperature was systematically tuned. At 180 °C, the resulting NAM-CDs developed a pyridine-rich surface characterized by maximized pyrrolic-N content and enhanced amide bond formation, facilitating efficient energy transfer from the carbon core to surface states. This optimized electronic structure synergistically enhanced both red fluorescence emission and photothermal conversion efficiency. The pyridine-rich NAM-CDs exhibited excellent biocompatibility, specific nuclear retention through Ki67-mediated interactions in cancer cells, and potent photothermal tumor ablation upon 660 nm laser irradiation in vivo, achieving complete tumor regression without recurrence over a 30-day observation period. By harnessing the inherent Ki67 affinity of NAM, this work provides a facile strategy for imparting tumor-targeting capability to photothermal agents, opening a new avenue for proliferation-marker-directed cancer therapy.
Background
Photothermal therapy for cancer is limited by the lack of tumor-specific targeting. This study addresses this issue by utilizing nicotinamide's affinity for Ki67, a marker of tumor proliferation, to create a targeted photothermal nanomaterial. The research aims to enhance the specificity and efficacy of photothermal agents in cancer treatment.
Methods
NAM-derived carbon dots were synthesized using a one-step solvothermal method. The study employed dynamic molecular docking simulations to assess binding affinity to Ki67. The synthesis temperature was optimized to enhance photophysical properties. In vivo experiments involved 660 nm laser irradiation to evaluate tumor ablation efficacy.
Results
NAM-CDs exhibited a binding energy of -7.7 kcal/mol to Ki67, compared to -3.8 kcal/mol for free NAM. The optimized NAM-CDs demonstrated enhanced red fluorescence emission and photothermal conversion efficiency. In vivo, NAM-CDs achieved complete tumor regression with no recurrence over 30 days, indicating effective tumor ablation.
Interpretation
The study suggests that NAM-CDs have potential as targeted photothermal agents due to their enhanced binding to Ki67 and effective tumor ablation in vivo. However, the clinical significance remains uncertain without human trials. The results are promising but require further validation in human models to assess translatability.
Key findings
- Binding energy of NAM-CDs to Ki67 was -7.7 kcal/mol.
- Free NAM binding energy to Ki67 was -3.8 kcal/mol.
- NAM-CDs achieved complete tumor regression in vivo over 30 days.
- NAM-CDs exhibited specific nuclear retention in cancer cells.
- Photothermal conversion efficiency was enhanced by pyridine-rich surface.
Limitations
- Species not specified in vivo study.
- Sample size not reported.
- Preclinical model, not human data.
- Short 30-day follow-up period.