الفهرس 
CHAPTER 1 INTRODUCTION & LITERATURE REVIWOnly 14 pages are availabe for public view
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Abstract
The current study presents a bimodal therapeutic platform based on su-perparamagnetic iron oxide nanoparticles (SPIONs), poly(N-isopropylacylamide) (PNIPAAm), and a Poly (ADP-ribose) polymer-ase-1(PARP-1) inhibitor; 5-aminoisoquinoline (5-AIQ). The magnetic thermoresponsive nanocomposite (MTN) was synthesized in a core-shell morphology by in situ free-radical polymerization of N-isopropylacrylamide in the presence of the ferrofluid of 11 nm SPIONs cores. The composite was allowed to swell in various concentrations of the drug (5-AIQ) forming drug-loaded magnetic thermoresponsive nanocomposite (MTN.5-AIQ). Bimodal therapy implies that the pre-sented drug loaded core-shell structure (MTN.5-AIQ) has the capability of elevating the tumor tissue temperature (hyperthermia) through the superparamagnetic iron oxide core and simultaneously releasing a drug 5-AIQ.The capability of Superparamagnetic iron oxide nanoparticles (SPIONs) as successful hyperthermia agents was proved by measuring the specific absorption rate of SPIONs by an induction heater. Poly(N-isopropylacrylamide (PNIPAAm) is the most commonly used ther-moresponsive polymer that responds to a change in temperature by changing its solubility and exhibiting sol-gel transition. SPIONs and PNIPAAm constitute the magnetic thermoresponsive nanocomposite (MTN). To the author’s knowledge, the combination of magnetic nano-composites with PARP-1 modifying agents has not been previously in-vestigated.
Structural characterization of the formed composite was studied via various experimental tools; X-ray diffraction (XRD), transmission elec-tron microscopy (TEM), Fourier transform infrared (FTIR) spectrosco-py, energy dispersive X-ray (EDX) spectroscopy, and thermal gravimet-ric analysis (TGA). The vibrating sample magnetometer (VSM) was used to study the magnetic properties of the composite. Specific ab-sorption rates (SARs) of SPIONs were measured by an induction heat-er. The lower critical solution temperatures (LCSTs) of PNIPAAm, MTN and MTN.5-AIQ were determined by the differential scanning calorimetry (DSC). The cloud point temperature of PNIPAAm was measured by a turbidimeter and UV-visible spectroscopy. The results confirmed the formation of (MTN) with excellent potential for hyper-thermia. A high drug loading efficiency (85.72%) was obtained with convenient temperature-dependent drug release kinetics. In vivo and in vitro studies were used to assess biocompatibility and cytotoxic effica-cy respectively. MTN.5-AIQ administration (to normal mice) resulted in normal hepatic and renal function, as well as a lower toxic effect on normal tissue. In addition, the drug-loaded composite effectively inhib-ited Caco-2 cells viability upon incubation. Based on the obtained re-sults, the proposed therapeutic platform can be considered as a novel, promising candidate for bimodal therapy of colorectal adenocarcinoma (CRC) exhibiting a PARP-1 overexpression.