Sialic acid-receptor targeted Epirubicin and Naringin-loaded sialic acid-conjugated silk fibroin nanoparticles for enhanced lung cancer treatment

Abstract Lack of specificity, high burden of toxicity, and low bioavailability are the significant hurdles of conventional chemotherapies. Upregulated sialic acid receptors on the plasma membrane of lung cancer cells could be promising drug delivery targets for effective lung cancer treatment. In this view, the present study aimed to fabricate sialic acid (SA)-conjugated epirubicin (Epi) and naringin (NA)-loaded silk fibroin (SF) nanoparticles (SA-Epi-NA-SF-NPs) for selective delivery and enhanced lung cancer treatment. SF protein was initially extracted from silk cocoons, and the SA-conjugated SF was synthesized using simple EDC-conjugation chemistry. Later, the desolvation cross-linking technique was used to fabricate SA-Epi-NA-SF-NPs by encapsulating Epi and NA into an SA-conjugated SF. Various characterization methods were employed to confirm the physicochemical properties of SA-Epi-NA-SF-NPs. The fabricated SA-Epi-NA-SF-NPs ranged in size from 100 to 400 nm and had a spherical, crystalline nature. Epi and NA had encapsulation efficiency and loading capacity of 83 ± 1.5%, 80 ± 12%, 8.34 ± 0.9%, and 8.16 ± 0.3% into SA-conjugated SF, respectively. Drug release was substantially higher at pH 5.4 (84.46 ± 1.29% Epi and 70.99 ± 1.56% NA) than at pH 7.4. The cytotoxic potential of SA-Epi-NA-SF-NPs against A549 cells could diminish the viable number of cells after 24 h of treatment, and 13.16 µg×mL − 1 was observed as an IC 50 . The higher intracellular accumulation of Epi and NA in A549 cells targets mitochondria and the nucleus and causes apoptosis. Based on these outcomes, SA-Epi-NA-SF-NPs could have high therapeutic potential for lung cancer treatment, specifically targeting sialic acid receptors on A549 cells.