MIL-100(Fe)-Magnetite-Chitosan nanocomposite for targeted EPR delivery: synthesis, characterization, and DFT insights

Résumé

Abstract Developing advanced chemotherapeutic drug delivery systems (DDS) is critical for expanding the therapeutic index and reducing the off-target toxicity of potent anticancer agents. In this study, a novel multifunctional nanocomposite, CS/M/MIL, was engineered by integrating magnetite (M) nanoparticles and chitosan (CS) into a metal–organic framework (MOF), MIL-100(Fe), using a modified hydrothermal method. This platform was utilized to encapsulate the anticancer drug epirubicin (EPR), achieving a remarkably high drug entrapment efficiency (EE) of 89.4%. Physicochemical characterization, including XRD and SEM, confirmed successful composite formation and structural integrity, with the modified CS/M/MIL showing a particle size increase to approximately 400 nm compared to the pristine MOF. Textural analysis revealed a transition from a highly microporous structure (BET surface area: 1804.68 m 2 /g) to a hierarchical macroporous architecture (50.95 m 2 /g) following functionalization. In vitro release kinetics demonstrated a pH-responsive behavior, with significantly accelerated drug release in acidic conditions (pH 5.0) simulating the acidic endo/lysosomal compartments. Biological evaluations against MCF-7 breast cancer cells revealed that the EPR-loaded nanocomposite significantly enhanced therapeutic efficacy, yielding an IC 50 value of 7.57 µg/mL. Furthermore, flow cytometric analysis confirmed that the system promotes substantial apoptosis (31.66%) and induces G2/M phase cell cycle arrest. The significance and novelty of this work lie in the synergistic integration of magnetic responsiveness, biocompatible polymeric coating, and high-porosity MOF architecture into a single platform. Additionally, density functional theory (DFT) calculations provided unique mechanistic insights, identifying Fe 3+ coordination and hydrogen bonding as the primary drivers for the high affinity between EPR and the nanocarrier. These findings position CS/M/MIL as a superior, targeted carrier for anthracycline-type drugs, offering a pathway to improved clinical outcomes with reduced systemic side effects.

Citer ce document

Accès au document

Texte intégral en lecture en ligne, réservé aux abonnés SPHAERO et aux membres de l'institution. Se connecter

Auteur(s)

Statistiques

Consultations : 1

Téléchargements : 0