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<p>This study reports a novel targeted cancer therapy platform based on luteolin-loaded mesoporous silica nanoparticles functionalized with folic acid (Lu-MSN-FA NPs). MSNs were synthesized via a CTAB-templated sol-gel process employing tetraethylorthosilicate (TEOS) in an ammonium hydroxide-catalyzed system at 45&#xa0;°C, followed by surfactant removal through acidic methanol reflux. The resulting NPs were surface-modified with (3-aminopropyl) triethoxysilane (APTS) and conjugated with FA using EDC/NHS activation to enable selective receptor-mediated uptake in cancer cells. The characteristics of Lu-MSN-FA NPs were evaluated using dynamic light scattering (DLS) and field-emission scanning electron microscopy (FESEM), revealing uniform, spherical particles with a favorable size for cellular uptake. Luteolin was successfully incorporated into the functionalized MSNs, achieving an encapsulation efficiency of 83.10%. Release assays indicated a controlled and sustained release pattern under experimental conditions. In vitro studies on AGS, HT-29, A2780, and A2058 cell lines revealed concentration-dependent cytotoxicity, with the highest sensitivity observed in A2780 cells. Cytotoxicity assays revealed the concentration-dependent cytotoxic effect of Lu-MSN-FA NPs, particularly on A2780 cells, with an IC50 of 5.7&#xa0;µg/mL. Annexin V-FITC/PI dual staining and DAPI assays confirmed apoptosis induction. At the same time, real-time PCR demonstrated significant modulation of apoptosis-related genes (caspase 9 and p21) along with reduced expression of the antioxidant enzyme SOD. The Lu-MSN-FA NPs also exhibited robust free radical scavenging activity, underscoring their dual therapeutic potential. These findings indicate the effective formulation and controlled release performance of Lu-MSN-FA NPs, emphasizing their promise as a targeted delivery system for enhanced cancer therapy.</p>

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The potential of luteolin-conjugated mesoporous silica nanoparticles functionalized with folic acid in targeted cancer therapy in an in vitro model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月24日

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  • Maryam Hosseini,
  • Masoud Homayouni Tabrizi,
  • Bita Behboodian,
  • Mozhgan Soltani

摘要

This study reports a novel targeted cancer therapy platform based on luteolin-loaded mesoporous silica nanoparticles functionalized with folic acid (Lu-MSN-FA NPs). MSNs were synthesized via a CTAB-templated sol-gel process employing tetraethylorthosilicate (TEOS) in an ammonium hydroxide-catalyzed system at 45 °C, followed by surfactant removal through acidic methanol reflux. The resulting NPs were surface-modified with (3-aminopropyl) triethoxysilane (APTS) and conjugated with FA using EDC/NHS activation to enable selective receptor-mediated uptake in cancer cells. The characteristics of Lu-MSN-FA NPs were evaluated using dynamic light scattering (DLS) and field-emission scanning electron microscopy (FESEM), revealing uniform, spherical particles with a favorable size for cellular uptake. Luteolin was successfully incorporated into the functionalized MSNs, achieving an encapsulation efficiency of 83.10%. Release assays indicated a controlled and sustained release pattern under experimental conditions. In vitro studies on AGS, HT-29, A2780, and A2058 cell lines revealed concentration-dependent cytotoxicity, with the highest sensitivity observed in A2780 cells. Cytotoxicity assays revealed the concentration-dependent cytotoxic effect of Lu-MSN-FA NPs, particularly on A2780 cells, with an IC50 of 5.7 µg/mL. Annexin V-FITC/PI dual staining and DAPI assays confirmed apoptosis induction. At the same time, real-time PCR demonstrated significant modulation of apoptosis-related genes (caspase 9 and p21) along with reduced expression of the antioxidant enzyme SOD. The Lu-MSN-FA NPs also exhibited robust free radical scavenging activity, underscoring their dual therapeutic potential. These findings indicate the effective formulation and controlled release performance of Lu-MSN-FA NPs, emphasizing their promise as a targeted delivery system for enhanced cancer therapy.