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<p>High-grade gliomas are devastating cancers with dismal prognosis, largely because current chemotherapeutics fail to cross the blood–brain barrier and lack tumor-cell specificity. Nanotechnology aims to overcome these limitations through targeted drug delivery. Here, a quadruple-conjugated nanomodel was synthesized using carbon dots (C-dots) as biocompatible nanocarriers via a one-pot reaction that covalently links two targeting peptides and two anticancer agents. The short peptide (shPep-1) targets the tumor-restricted receptor IL13Rα2, whereas the long peptide (lnPep-1) contains a nuclear localization signal for enhanced intracellular trafficking. Therapeutic cargo consists of epirubicin and the temozolomide metabolite 5-aminoimidazole-4-carboxamide. This nanomodel displays potent cytotoxicity in multiple high-grade glioma cell lines at 50 nM while remaining relatively non-toxic to normal cells (IC₅₀ &gt; 2 µM). Despite a lower drug-loading capacity than single-peptide formulations, it induced greater glioma cell death, underscoring the enhanced therapeutic synergy of its dual-peptide, dual-drug design. Fluorescence studies confirm superior uptake and nuclear delivery, establishing C-dots as a stable, cost-effective, modular platform for next-generation personalized cancer nanotherapies.</p><p></p>

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Development of a quadruple-conjugated carbon dot nanomodel for targeted glioma therapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月30日

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  • Emel Kirbas Cilingir,
  • Sajini D. Hettiarachchi,
  • Parth Rathee,
  • Yiqun Zhou,
  • Braulio CLB Ferreira,
  • Lukun Wang,
  • Annu Joji,
  • Carlos M. Gonzalez,
  • Maria J. Moreno Hollweg,
  • Mehrdad Shiri,
  • Kun Wang,
  • Rajeev Prabhakar,
  • Steven Vanni,
  • Roger M. Leblanc,
  • Regina M. Graham

摘要

High-grade gliomas are devastating cancers with dismal prognosis, largely because current chemotherapeutics fail to cross the blood–brain barrier and lack tumor-cell specificity. Nanotechnology aims to overcome these limitations through targeted drug delivery. Here, a quadruple-conjugated nanomodel was synthesized using carbon dots (C-dots) as biocompatible nanocarriers via a one-pot reaction that covalently links two targeting peptides and two anticancer agents. The short peptide (shPep-1) targets the tumor-restricted receptor IL13Rα2, whereas the long peptide (lnPep-1) contains a nuclear localization signal for enhanced intracellular trafficking. Therapeutic cargo consists of epirubicin and the temozolomide metabolite 5-aminoimidazole-4-carboxamide. This nanomodel displays potent cytotoxicity in multiple high-grade glioma cell lines at 50 nM while remaining relatively non-toxic to normal cells (IC₅₀ > 2 µM). Despite a lower drug-loading capacity than single-peptide formulations, it induced greater glioma cell death, underscoring the enhanced therapeutic synergy of its dual-peptide, dual-drug design. Fluorescence studies confirm superior uptake and nuclear delivery, establishing C-dots as a stable, cost-effective, modular platform for next-generation personalized cancer nanotherapies.