Formulation of folic acid-decorated β-cyclodextrin-based magnetic nanoparticles hybrid nanotherapeutic for targeted delivery of chlorogenic acid

Abstract

Neuroblastoma, the most common extracranial pediatric tumor, has attracted considerable attention owing to the promising anticancer potential of chlorogenic acid (ChA). However, the utility of ChA is restricted by off-target effects. To overcome this limitation, we developed chlorogenic acid-loaded folic acid-conjugated β-cyclodextrin magnetic nanoparticles (Fe₃O₄-β-CD-FA@ChA) as a novel targeted delivery system. This study aimed to design, synthesize, and evaluate Fe₃O₄-β-CD-FA nanoparticles for the customized release, tumor-specific targeting, anticancer activity, and potential diagnostic application of ChA against neuroblastoma. In brief, the Fe₃O₄ core was synthesized by co-precipitation using Fe²⁺/Fe³⁺ salts and functionalized with β-cyclodextrin (β-CD) and FA through carbodiimide coupling. Here, ChA was loaded via an incubation diffusion method, enabling efficient encapsulation through non-covalent interactions. The resulting nanohybrids exhibited a mean size of 688.1 nm, carried a negative surface charge (−16 mV), and displayed irregular morphology. Customized drug release was achieved, with 34.38 % and 58.34 % ChA released over 48 h at pH 6.8 and 5.5, respectively. In vitro studies on SH-SY5Y neuroblastoma cells demonstrated significantly enhanced cytotoxicity (71.20 ± 0.92 %) compared to free ChA (40.95 ± 0.60 %), attributable to FA-mediated receptor targeting. Magnetic resonance imaging (MRI) confirmed superior intracellular accumulation and enhanced contrast in targeted cells. In conclusion, these findings highlight the potential of β-CD to design the Fe₃O₄-β-CD-FA@ChA nanohybrids in achieving targeted delivery, improved therapeutic efficacy, pH-responsive drug release, and theranostic capability. This β-CD-mediated nanoplatform offers a promising strategy for neuroblastoma treatment and warrants further investigation with other bioactive compounds.