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<p>We developed a disulfide bond-modified chitosan (CS-SS) into a nano-formulation for delivery of Polo-like kinase 1 (PLK1) siRNA (siRNA-CS-SS). The formation of CS-SS was confirmed by Fourier transform infrared and proton nuclear magnetic resonance analyses. The resulting siRNA-CS-SS exhibited a spherical morphology with uniform dispersion, a particle size of 226.72 ± 1.36&#xa0;nm, a polydispersity index (PDI) of 0.196 ± 0.02, a zeta potential of + 18.53 ± 0.70 mV, and an encapsulation efficiency of 85.21 ± 1.17%. The formulation showed no significant changes in particle size, PDI, or zeta potential during 7 days of storage at 4&#xa0;°C (<i>p</i> &gt; 0.05), while glutathione (GSH) triggered nanoparticle disassembly, leading to increased particle size and enhanced siRNA release. siRNA-CS-SS showed no apparent cytotoxicity in L6 cells (cell viability &gt; 90% at 200 nM) and no significant hemolytic activity (hemolysis rate &lt; 5%) within the tested concentration range. In HCT116 cells, siRNA-CS-SS reduced PLK1 protein expression by approximately 70%, and in a colitis-associated cancer (CAC) mouse model, it decreased PLK1 expression by roughly 65% in colon tissue while restoring body weight to near-normal levels, exerting potent anti-colon tumor effects in vitro and in vivo. Compared with previously reported redox-responsive chitosan systems, the CS-SS nanocarrier offered improved water solubility and was applied for the first time in delivering PLK1 siRNA to a CAC model. These findings highlight siRNA-CS-SS as a promising strategy for colon cancer therapy.</p> Graphical Abstract <p></p>

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Targeted Anti-Colon Tumor Effect of PLK1 siRNA Loaded by Disulfide Bond-Modified Chitosan

  • 期刊论文

  • 发表日期：

    2026年6月25日

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  • Qi Shen,
  • Tingwang Jiang,
  • Zhiliang Shi,
  • Chenyao Peng,
  • Ying Liu,
  • Senlin Xue,
  • Yize Lv,
  • Guoqiang Zhou

摘要

We developed a disulfide bond-modified chitosan (CS-SS) into a nano-formulation for delivery of Polo-like kinase 1 (PLK1) siRNA (siRNA-CS-SS). The formation of CS-SS was confirmed by Fourier transform infrared and proton nuclear magnetic resonance analyses. The resulting siRNA-CS-SS exhibited a spherical morphology with uniform dispersion, a particle size of 226.72 ± 1.36 nm, a polydispersity index (PDI) of 0.196 ± 0.02, a zeta potential of + 18.53 ± 0.70 mV, and an encapsulation efficiency of 85.21 ± 1.17%. The formulation showed no significant changes in particle size, PDI, or zeta potential during 7 days of storage at 4 °C (p > 0.05), while glutathione (GSH) triggered nanoparticle disassembly, leading to increased particle size and enhanced siRNA release. siRNA-CS-SS showed no apparent cytotoxicity in L6 cells (cell viability > 90% at 200 nM) and no significant hemolytic activity (hemolysis rate < 5%) within the tested concentration range. In HCT116 cells, siRNA-CS-SS reduced PLK1 protein expression by approximately 70%, and in a colitis-associated cancer (CAC) mouse model, it decreased PLK1 expression by roughly 65% in colon tissue while restoring body weight to near-normal levels, exerting potent anti-colon tumor effects in vitro and in vivo. Compared with previously reported redox-responsive chitosan systems, the CS-SS nanocarrier offered improved water solubility and was applied for the first time in delivering PLK1 siRNA to a CAC model. These findings highlight siRNA-CS-SS as a promising strategy for colon cancer therapy.

Graphical Abstract