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Article Abstract
Temozolomide (TMZ) is the frontline alkylating agent in melanoma cancer treatment but has a narrow therapeutic index due to its hemotoxicity. Targeting Wnt/β-catenin signaling could enhance the effectiveness of alkylating drugs and offer a promising approach to improve chemosensitivity. Nevertheless, developing a satisfactory method to efficiently inhibit Wnt/β-catenin for synergistic combination therapy remains an unmet goal. In this study, we synthesized aloe vera-derived carbon dots (CDs) through a one-step hydrothermal treatment，which exhibited both self-inhibition of Wnt/β-catenin and capabilities for bioimaging, thereby address the challenges of traditional Wnt/β-catenin inhibitors. Synthesized CDs were subsequently utilized in the delivery of TMZ to achieve synergistic treatment via inhibiting Wnt/β-catenin and downregulating O6-Methylguanine-DNA Methyltransferase, resulting in increasing DNA damage. Additionally, the pH-sensitive material (ppCDs@TMZ) was prepared by coating PAE-PEG (pp) onto CDs@TMZ and achieving remarkable antitumor efficacy in vivo without significant toxicity on normal tissues. In conclusion, this research provides an innovative approach for inhibiting Wnt/β-catenin to significantly enhance effectiveness of combination therapy, shedding light on the future application of Wnt/β-catenin based nano-agents in cancer therapy.
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| http://dx.doi.org/10.1016/j.bioorg.2025.108919 | DOI Listing |
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