Dielectric-responsive liposomal 5-fluorouracil/ZnO nanoparticles with anticancer and antibacterial activity


Dabagh S., GHORBANPOOR H., Tomsuk Ö., Leimane M., Haris S. A., UYSAL O., ...Daha Fazla

Materials Today Chemistry, cilt.58, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 58
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.mtchem.2026.104108
  • Dergi Adı: Materials Today Chemistry
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Compendex, INSPEC
  • Anahtar Kelimeler: Charge-carrier mobility, Chemo-antimicrobial therapy, Drug delivery, Liver co-culture model, Multifunctional nanocarriers
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

The development of multifunctional nanocarriers capable of targeting cancer progression and infection-related complications remains a major challenge in nanomedicine. In this work, novel dielectric-responsive liposomal 5-fluorouracil/zinc oxide NPs (LPs@5-FU/ZnO NPs) were successfully synthesized by a simple one-step method for potential dual chemo-antimicrobial therapy. The synthesized nanocarriers integrated 5-fluorouracil as an anticancer agent, the antibacterial properties of ZnO NPs, and the controlled-release capacity of liposomal encapsulation. Physicochemical characterization using different spectroscopic and microscopic methods revealed successful drug loading and liposome formation. The hydrodynamic particle size increased from ∼40 nm for bare ZnO NPs to ∼70 nm after 5-FU loading and further to ∼100 nm after liposomal encapsulation. The surface charge shifted from ⁓ 40 mV for ZnO NPs to ⁓ −30 mV for LPs@5-FU/ZnO NPs, indicating enhanced colloidal stability and successful lipid coating. HPLC analysis showed excellent analytical linearity (R2 = 0.9905), while release studies revealed a pH-responsive sustained-release profile with increased drug release under acidic conditions (pH 5.0) and slower release at physiological pH (7.4), supporting tumor-targeted drug delivery. The dielectric constant (ε′), dielectric loss (ε″) and loss tangent (tan δ) are remarkably reduced after loading with 5-FU and encapsulation in liposomes. This was due to improved NPs stability and controlled drug release behavior, owing to reduced charge-carrier mobility, suppressed oxygen-vacancy-related polarization, and improved interfacial interactions among the ZnO, 5-FU, and phospholipid layers. Antibacterial activity against both Escherichia coli and Staphylococcus aureus showed that the LPs@5-FU/ZnO NPs had lower MIC values (2.5 mg mL−1) than the non-encapsulated 5-FU/ZnO NPs (3.5 mg mL−1), confirming the enhanced antimicrobial efficacy upon encapsulation. In the HepG2/EA. hy926 liver co-culture model, non-encapsulated 5-FU/ZnO NPs exhibited pronounced concentration-dependent cytotoxicity, with cell viability decreasing below 50% at 1.95 mg mL−1, accompanied by increased LDH release and morphological alterations. In contrast, LPs@5-FU/ZnO NPs exhibited substantially lower acute cytotoxicity and largely preserved cell viability and membrane integrity despite being tested at equivalent ZnO and 5-FU doses. This reduced acute response may reflect liposomal shielding and slower release kinetics. The results indicate that LPs@5-FU/ZnO NPs constitute a promising multifunctional nanotherapeutic platform that integrates controlled 5-FU delivery, dielectric-responsive behavior, and enhanced antibacterial activity, presenting significant potential for advanced nanomedicine applications.