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<p>Skin cancer, with its steadily increasing incidence, has driven growing interest in using hydrogels as effective platforms for localized drug delivery. This study developed a dual-layer scaffold of nanofibers and hydrogel to incorporate 5-fluorouracil (5-FU) and quercetin (Que) for enhanced melanoma cell inhibition. The scaffold consisted of a hydrogel composed of sodium alginate (SA) and chitosan (CS), along with a layer of nanofibers (NFs) fabricated from polycaprolactone (PCL). The relevant physicochemical characterizations, cytotoxicity assessments, and cell migration analyses in melanoma A375 cells were conducted. The evaluation of the hydrogel layer of the scaffold revealed a uniform, homogeneous, and smooth surface devoid of macroscopic roughness. It featured a highly porous microstructure characterized by interconnected micrometre-scale pores. The nanofibrous layer consisted of uniform, defect-free fibers with diameters averaging approximately 134 ± 35&#xa0;nm, resulting in a consistent and homogeneous structure. Infrared spectroscopic analysis utilizing Fourier transform verified the successful incorporation of chemotherapeutic agents within the hydrogel. Furthermore, the scaffold demonstrated a hydrophilic surface, high porosity, and effective liquid absorption capabilities. The degradation profile indicated a prolonged deterioration period of approximately 10 days. The scaffold shows a sustained and controlled drug release profile. Additionally, the 5-FU/Que-loaded scaffold demonstrated a significantly enhanced cytotoxic effect of 90% and a pronounced inhibition of melanoma cell migration relative to alternative formulations. Therefore, the 5-FU/Que co-loaded scaffold presents a promising approach for effectively eliminating skin melanoma tumors while minimizing the adverse side effects of chemotherapy.</p> Graphical Abstract <p></p>

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Engineering a dual-layer hydrogel–nanofiber scaffold co-loaded with 5-FU and quercetin for enhanced melanoma cell inhibition

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Bita Jahanshahi,
  • Shirin Shojaei,
  • Maryam Doostan,
  • Kamyar Khoshnevisan,
  • Hadi Baharifar,
  • Hassan Maleki

摘要

Skin cancer, with its steadily increasing incidence, has driven growing interest in using hydrogels as effective platforms for localized drug delivery. This study developed a dual-layer scaffold of nanofibers and hydrogel to incorporate 5-fluorouracil (5-FU) and quercetin (Que) for enhanced melanoma cell inhibition. The scaffold consisted of a hydrogel composed of sodium alginate (SA) and chitosan (CS), along with a layer of nanofibers (NFs) fabricated from polycaprolactone (PCL). The relevant physicochemical characterizations, cytotoxicity assessments, and cell migration analyses in melanoma A375 cells were conducted. The evaluation of the hydrogel layer of the scaffold revealed a uniform, homogeneous, and smooth surface devoid of macroscopic roughness. It featured a highly porous microstructure characterized by interconnected micrometre-scale pores. The nanofibrous layer consisted of uniform, defect-free fibers with diameters averaging approximately 134 ± 35 nm, resulting in a consistent and homogeneous structure. Infrared spectroscopic analysis utilizing Fourier transform verified the successful incorporation of chemotherapeutic agents within the hydrogel. Furthermore, the scaffold demonstrated a hydrophilic surface, high porosity, and effective liquid absorption capabilities. The degradation profile indicated a prolonged deterioration period of approximately 10 days. The scaffold shows a sustained and controlled drug release profile. Additionally, the 5-FU/Que-loaded scaffold demonstrated a significantly enhanced cytotoxic effect of 90% and a pronounced inhibition of melanoma cell migration relative to alternative formulations. Therefore, the 5-FU/Que co-loaded scaffold presents a promising approach for effectively eliminating skin melanoma tumors while minimizing the adverse side effects of chemotherapy.

Graphical Abstract