Galactomannan armed superparamagnetic iron oxide nanoparticles as a folate receptor targeted multi-functional theranostic agent in the management of cancer

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) represent a versatile class of theranostics with profound applications in biomedicine. An eco-friendly modification of SPIONs was attempted with a 110 kDa galactomannan (PSP001) isolated from the fruit rind of Punica granatum. The PSP001 appended SPIONs favor unique advantages including tumor-targeted accumulation and improved biocompatibility. The antineoplastic agent methotrexate (MTX) was covalently attached with the galactomannan in the SPIONs to yield PSP-IO NPs that demonstrated a reduction-sensitive drug release kinetics favoring MTX accumulation selectively in the tumor cells. Folate receptor (FR) targeted cancer cell uptake followed by the stimuli-responsive release of the payload favored improved biocompatibility and lack of toxicity in BALB/c mice. Superior tumor reduction capacity with marked survival benefits was observed in Ehrlich ascites carcinoma (EAC) bearing solid tumor mice. Phantom imaging of the carrier (PSP-IO) and the drug-loaded (PSP-IO-MTX NPs) nano-constructs generated an r2 relaxivity of 335.3 mM^-1 S^-1 and 333.79 mM^-1 S^-1 respectively indicating the remarkable contrast in magnetic resonance imaging (MRI) which was confirmed in syngraft and xenograft murine models. It is worth mentioning that PSP-IO-MTX NPs with a facile fabrication process offered an affordable nano-theranostic agent for targeted concurrent MR imaging and FR-mediated targeted tumor therapy favoring bed-side applications.

Keywords: Cancer; Drug delivery; Iron oxide nanoparticles; Magnetic resonance imaging; Polysaccharide.