Folic Acid-Doxorubicin-Double-Functionalized-Lipid-Core Nanocapsules: Synthesis, Chemical Structure Elucidation, and Cytotoxicity Evaluation on Ovarian (OVCAR-3) and Bladder (T24) Cancer Cell Lines

Abstract

Purpose

Folic acid-doxorubicin-double-functionalized-lipid-core nanocapsules (LNC-CS-L-Zn+2-DOX-FA) were prepared, characterized, and evaluated in vitro against ovarian and bladder cancer cell lines (OVCAR-3 and T24).

Methods

LNC-CS-L-Zn+2-DOX-FA was prepared by self-assembly and interfacial reactions, and characterized using liquid chromatography, particle sizing, transmission electron microscopy, and infrared spectroscopy. Cell viability and cellular uptake were studied using MTT assay and confocal microscopy.

Results

The presence of lecithin allows the formation of nanocapsules with a lower tendency of agglomeration, narrower size distributions, and smaller diameters due to an increase in hydrogen bonds at the surface. LNC-L-CS-Zn+2-DOX-FA, containing 98.00 ± 2.34 μg mL−1 of DOX and 105.00 ± 2.05 μg mL−1 of FA, had a mean diameter of 123 ± 4 nm and zeta potential of +12.0 ± 1.3 mV. After treatment with LNC-L-CS-Zn+2-DOX-FA (15 μmol L−1 of DOX), T24 cells had inhibition rates above 80% (24 h) and 90% (48 h), whereas OVCAR-3 cells showed inhibition rates of 68% (24 h) and 93% (48 h), showing higher cytotoxicity than DOX.HCl. The fluorescent-labeled formulation showed a higher capacity of internalization in OVCAR-3 compared to T24 cancer cells.

Conclusion

Lecithin favored the increase of hydrogen bonds at the surface, leading to a lower tendency of agglomeration for nanocapsules. LNC-CS-L-Zn+2-DOX-FA is a promising therapeutic agent against tumor-overexpressing folate receptors.

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Cé, R., Lavayen, V., Couto, G.K. et al. Folic Acid-Doxorubicin-Double-Functionalized-Lipid-Core Nanocapsules: Synthesis, Chemical Structure Elucidation, and Cytotoxicity Evaluation on Ovarian (OVCAR-3) and Bladder (T24) Cancer Cell Lines. Pharm Res 38, 301–317 (2021). https://doi.org/10.1007/s11095-021-02989-y

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Key words

  • doxorubicin
  • folic acid
  • lipid-core nanocapsules
  • OVCAR-3: ovarian cancer line
  • T24: bladder cancer line