Development and bioevaluation of controlled release 5-aminoisoquinoline nanocomposite: a synergistic anticancer activity against human colon cancer

Abstract

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. Magnetic thermoresponsive nanocomposite MTN was synthesized via an in situ free radical polymerization of thermo-responsive (N-isopropylacrylamide) (NIPAAm) monomer in the presence of 11-nm monodisperse SPIONs. The composite was allowed to swell in various concentrations of the PARP inhibitor: 5-aminoisoquinoline (5-AIQ) forming drug-loaded magnetic thermoresponsive nanocomposite (MTN-5.AIQ). Structural characterization of the formed composite is studied via various experimental tools. To assess the coil to globule transition temperature, the lower critical solution temperature (LCST) is determined by differential scanning calorimetry (DSC) method and the cloud point (Tp) is determined by turbidometry. Magnetic thermoresponsive nanocomposite (MTN) is formed 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 model, 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. Based on the obtained results, the proposed therapeutic platform can be considered as a novel, promising candidate for dual therapy of colorectal adenocarcinoma exhibiting a PARP-1 overexpression. as well as increased the inhabiting efficacy of 5-AIQ.

Keywords

• spions
• thermoresponsive polymer
• hyperthermia
• parp inhibitor
• pnipam