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<p>Cancer is the second greatest cause of death globally. It is a chronic, diverse disease that can present with a wide range of severe clinical symptoms. The objective of the current study was to assess the anticancer properties of chitosan-conjugated <i>Citrullus lanatus</i>–silver-titanium oxide bimetallic nanocomposites (Cl-CS-Ag@TiO₂ BMNCs) and their effect on the PI3K/AKT/mTOR signaling pathway in HeLa cervical cancer cells. These bioengineered nanocomposites offer an effective substitute therapeutic strategy with improved biocompatibility and potency by targeting and inhibiting the PI3K/AKT/mTOR signaling cascade in HeLa cervical cancer cells. <i>Citrullus lanatus</i> seed extract was used to create Cl-CS-Ag@TiO₂ BMNCs, which were then examined using XRD, DLS, zeta potential, EDX, SEM, and UV-vis spectroscopy. The MTT test was used to measure cytotoxicity in HeLa and normal Ect1/E6E7 cells. Intracellular levels of antioxidants and mitochondrial function (MMP, ATP) were assessed. AO/EtBr dual labelling was used for verifying apoptosis, and RT-PCR was used to evaluate the gene expression of Bax, Bad, Bcl-2, and PI3K/AKT/mTOR pathway markers. Dose-dependent cytotoxicity was observed in HeLa cells with an IC₅₀ of 7&#xa0;µg/mL while showing minimal toxicity to normal cervical Ect1/E6E7 cells. Additionally, the treatment altered mitochondrial function, lowering ATP and MMP values and increasing internal ROS, which may indicate oxidative stress-induced apoptosis. At the IC₅₀ dosage, 77.45% of cells were proven to be apoptotic by AO/EtBr dual labelling. Cl-CS-Ag@TiO₂ BMNCs effectively suppressed proliferation and induced apoptosis at the cellular level by upregulating pro-apoptotic genes (Bax, Bad), downregulating anti-apoptotic Bcl-2, and dramatically inhibiting the PI3K/AKT/mTOR signalling pathway. All things considered, biogenically generated Cl-CS-Ag@TiO₂ BMNCs have strong anticancer effects on cervical cancer cells. Before being used in clinical settings, more in vivo research is necessary to confirm the potential for therapy.</p> Graphical Abstract <p></p>

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Biogenic Chitosan-Conjugated Citrullus lanatus–Silver-Titanium Oxide Bimetallic Nanocomposites Exhibit Potent Anti-Cervical Cancer Activity Through PI3K/AKT/mTOR Axis Modulation

  • 期刊论文

  • 发表日期：

    2026年1月19日

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  • Yiming Zhang,
  • Fangwei Tu,
  • Hongfang Pan

摘要

Cancer is the second greatest cause of death globally. It is a chronic, diverse disease that can present with a wide range of severe clinical symptoms. The objective of the current study was to assess the anticancer properties of chitosan-conjugated Citrullus lanatus–silver-titanium oxide bimetallic nanocomposites (Cl-CS-Ag@TiO₂ BMNCs) and their effect on the PI3K/AKT/mTOR signaling pathway in HeLa cervical cancer cells. These bioengineered nanocomposites offer an effective substitute therapeutic strategy with improved biocompatibility and potency by targeting and inhibiting the PI3K/AKT/mTOR signaling cascade in HeLa cervical cancer cells. Citrullus lanatus seed extract was used to create Cl-CS-Ag@TiO₂ BMNCs, which were then examined using XRD, DLS, zeta potential, EDX, SEM, and UV-vis spectroscopy. The MTT test was used to measure cytotoxicity in HeLa and normal Ect1/E6E7 cells. Intracellular levels of antioxidants and mitochondrial function (MMP, ATP) were assessed. AO/EtBr dual labelling was used for verifying apoptosis, and RT-PCR was used to evaluate the gene expression of Bax, Bad, Bcl-2, and PI3K/AKT/mTOR pathway markers. Dose-dependent cytotoxicity was observed in HeLa cells with an IC₅₀ of 7 µg/mL while showing minimal toxicity to normal cervical Ect1/E6E7 cells. Additionally, the treatment altered mitochondrial function, lowering ATP and MMP values and increasing internal ROS, which may indicate oxidative stress-induced apoptosis. At the IC₅₀ dosage, 77.45% of cells were proven to be apoptotic by AO/EtBr dual labelling. Cl-CS-Ag@TiO₂ BMNCs effectively suppressed proliferation and induced apoptosis at the cellular level by upregulating pro-apoptotic genes (Bax, Bad), downregulating anti-apoptotic Bcl-2, and dramatically inhibiting the PI3K/AKT/mTOR signalling pathway. All things considered, biogenically generated Cl-CS-Ag@TiO₂ BMNCs have strong anticancer effects on cervical cancer cells. Before being used in clinical settings, more in vivo research is necessary to confirm the potential for therapy.

Graphical Abstract