Multifunctional chitosan-bimetallic nanocarrier deliver 5-fluorouracil for enhanced treatment of pancreatic and triple-negative breast cancer

Abstract

This work aimed to prepare multifunctional aptamer-conjugated, photothermally responsive 5-fluorouracil (5fu)-loaded chitosan-bimetallic (Au/Pd) nanoparticles (APT-CS-5fu-Au/Pd NPs) for improved cytotoxicity in two cancer cell lines (PANC-1 and MDA-MD 231). The CS-5fu-Au/Pd NPs were polydispersed with a size of 34.43 ± 1.59 nm. FTIR analysis indicated the presence of CS, 5fu in CS-5fu-Au/Pd NPs. The 2 theta degrees in CS-5fu-Au/Pd NPs accounted for CS and Au/Pd. Additionally, AGE revealed the conjugation of APT in CS-5fu-Au/Pd NPs. The APT-CS-5fu-Au/Pd NPs (180 μg/mL) with NIR treatment increased the temperature to >50 °C. The optimized 5fu input was 0.075 % in CS-5fu-Au/Pd NPs, exhibiting a hydrodynamic size of 112.96 ± 17.23 nm, DEE of 64.2 ± 3.77 %, and DLE of 11.1 ± 0.65 %. A higher level of 5fu release (69.8 ± 2.78 %) was observed under pH 5.4 at 74 h. In conclusion, NIR-APT-CS-5fu-Au/Pd NPs did not cause toxicity to RBC and Egg CAM, but increased cytotoxicity in MDA-MB 231 and PANC-1 cells by triggering oxidative stress-mediated cell death.

Keywords: 5-Fluorouracil; Aptamer; Au/Pd nanoparticles; Chitosan; Cytotoxicity.