Magnetic Thermoresponsive Nanocomposite for Targeted PARP-1 in Colorectal Adenocarcinoma, an Approach for Tumor Dual Therapy

Abstract Background The current study presents a bimodal therapeutic platform for cancer treatment. Bimodal implies that the presented drug loaded core-shell structure is capable of elevating the tumor tissue temperature (hyperthermia) through the superparamagnetic iron oxide core and simultaneously release a Poly (ADP-ribose) polymerase-1(PARP-1)-modifying agent from the thermoresponsive shell. The capability of Superparamagnetic iron oxide nanoparticles (SPIONs) as successful hyperthermia agents is well established. Likewise, poly-n-isopropylacrylamide (PNIPAAm) is a widely used thermoresponsive polymer. Together, they constitute the magnetic thermoresponsive nanocomposite (MTN). To the authors knowledge, the combination of magnetic nanocomposites with PARP-1 modifying agents has not been investigated. Therefore, in this work, 5-aminoisoquinoline (5-AIQ) is loaded on the thermoresponsive polymer to constitute MTN.5-AIQ. Results Structural characterization of the formed composite is studied via various experimental tools. The lower critical solution temperature (LCST) is determined by differential scanning calorimetry (DSC) method. The results confirm the formation of magnetic thermoresponstive nanocomposite (MTN) with excellent potential for hyperthermia. A high drug loading efficiency (85.72%) is obtained with convenient temperature dependent drug release kinetics. Biocompatibility and cytotoxic efficacy are tested on an in vivo and in vitro colorectal-adenocarcinoma models, respectively. MTN.5-AIQ administration exhibits normal hepatic and renal functions as well as lower toxic effect on normal tissue. In addition, the composite effectively inhibits Caco-2 cells viability upon incubation. Conclusions Based on the obtained results, the proposed therapeutic platform can be considered as a novel, promising candidate as dual therapy for colorectal adenocarcinoma exhibiting a PARP-1 overexpression.