Targeted delivery of carboplatin via folic acid-functionalized NiFe ₂ O ₄ /silica nanocomposites for colon and cervical cancer therapy

Carboplatin, a platinum-based drug, offers similar mechanistic action with reduced toxicity, but is less potent than cisplatin. The present study reports the folic acid (FA)-mediated multifunctional magnetic nickel ferrite (30% NiFe 2 O 4 )/silica nanocomposite, which improves the potency of carboplatin for targeted cancer therapy. Three formulations, silica/carboplatin (Sil/Carbpt), NiFe 2 O 4 /silica/Carbpt (NiFe 2 O 4 /Sil/Carbpt), and NiFe 2 O 4 /silica/FA/Carbpt (NiFe 2 O 4 /Sil/FA/Carbpt), were formulated. NiFe 2 O 4 /silica/cisplatin (NiFe 2 O 4 /Sil/Cispt) was used for the comparative study. Additionally, 5% of FA was mixed as a composite with NiFe 2 O 4 /silica, while the carboplatin/nanocarrier ratio was maintained at 0.04. The crystallinity, textural, morphology, magnetization, and functional interactions are confirmed by various characterization techniques. The order of carboplatin release at pH 5.6 was NiFe 2 O 4 /Sil/FA/Carbpt > NiFe 2 O 4 /Sil/Carbpt > Sil/Carbpt. The diffusion mechanisms for drug release are limited to Fickian and non-Fickian diffusion mechanisms, without following the carriage (n > 0.89) or relaxation transport (n = 0.89) mechanisms. The nanoformulation cytotoxicity study of NiFe 2 O 4 /SiO 2 /FA/Carbpt and NiFe 2 O 4 /SiO 2 /Carbpt showed lower toxicity to normal cells (LC50:1054.43 µg/mL and 16542.78 µg/mL, respectively), and toxicity to colon (HCT 116, LC50:10.38 µg/mL and 8.73 µg/mL, respectively) and cervical cancer cells (HeLa LC 50 : 16.37 µg/mL and 11.69 µg/mL, respectively). The data show moderate toxicity, particularly in Human Foreskin Fibroblasts (HFF-1), with FA potentially enhancing the compound’s uptake. Lower LC 50 values in Human colon cancer cell line (HCT116) and HELA suggest selective toxicity towards cancer cells over non-cancerous HFF-1 cells. These findings clearly indicate that silanols of NiFe 2 O 4 /SiO 2 interact with FA through hydrogen bonding, while a stable amide bond between FA with Carbpt withstands the acidic/basic environment, targeting colon and cervical cancer cells.