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Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release, Delivery, Apoptosis Induction, and Gene Expression in Pancreatic Cancer Cells

202075 citationsOpen accessKafr el-Sheikh University

In plain language

Superparamagnetic iron oxide nanoparticles coated with dextran and conjugated with folic acid were developed to improve the targeted delivery and uptake of the cancer drug vinblastine in PANC-1 pancreatic cancer cells. Physical and chemical characterisation confirmed that the resulting nanocarriers were spherical, well-dispersed, and measured approximately 74 nanometres in diameter without visible aggregation. In laboratory cell tests, the functionalised nanocarrier displayed low inherent cytotoxicity while effectively delivering vinblastine to trigger cell death. Gene expression testing revealed that treatment activated caspase-3, NF-1, and PDL-1, while simultaneously inhibiting H-ras. These cellular responses demonstrated that the nanostructure curtails cancer cell proliferation and promotes apoptosis, indicating strong potential for targeted therapeutic delivery in pancreatic cancer cells.

Key takeaways

  • Dextran-coated and folic acid-conjugated magnetic nanoparticles successfully encapsulated and delivered vinblastine to PANC-1 pancreatic cancer cells.
  • The formulation formed spherical, stable nanostructures with an average diameter of 74 nanometres and no visible aggregation.
  • Treatment induced apoptosis in cancer cells and altered gene expression by activating caspase-3, NF-1, and PDL-1 while repressing H-ras.
  • The carrier demonstrated low baseline cytotoxicity alongside an ability to restrict pancreatic cancer cell proliferation.

Why it matters

Pancreatic cancer remains difficult to treat effectively using standard chemotherapy due to poor drug targeting and toxicity. Formulating targeted nanocarriers using magnetic iron oxide cores and folic acid targeting allows therapeutic agents such as vinblastine to reach cancer cells more selectively. Understanding how these nanostructures induce cell death and alter cancer gene pathways helps researchers design safer and more focused cancer therapies.

Commercialisation angle

This research provides early-stage laboratory evidence for a targeted nanocarrier system that could inform the formulation of future oncology therapeutics. The primary prospective users would be pharmaceutical developers and biotechnology companies working on targeted nanomedicine for solid tumours. Because the findings are based entirely on in vitro cell culture experiments, the formulation remains at an early discovery stage, requiring extensive preclinical animal testing and formulation optimisation before any clinical use.

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Abstract

In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and -45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of <i>caspase-3</i>, <i>NF-1</i>, <i>PDL-1</i>, and <i>H-ras</i> inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.

Research topics

  • Nanoparticle-Based Drug Delivery
  • Microtubule and mitosis dynamics
  • Graphene and Nanomaterials Applications

Sustainable Development Goals

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DOI: 10.3390/molecules25204721

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