الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
One of the most common cancers is breast cancer and it has a high incidence rate in all countries. The main lines of treatment for breast cancer are radiation therapy (RT), chemotherapy (CT), surgery and targeted therapy. Negative impact on health-related quality of life is the result of the several chemotherapy adverse effects such as hair loss, depressed immunity, fatigue, gastrointestinal disturbances and neutropenia. Nanoparticles (NPs) show interesting characteristics as small sizes, large surface-tovolume ratios, high drug loading capacity, self-assembly capacity, and biocompatibility.
Consequently, they have the potential to increase both selectivity and potency of chemical, physical, and biological approaches for eliciting cancer cell death while lowering the toxicity to nonmalignant cells. Silk sericin (SS) is a glue-like glycoprotein that is extracted from the cocoons of silkworm. It is easy to be purified by degumming process. Being highly hydrophilic allowing ease of delivery by injection thus it can be considered as an ideal candidate for NPs preparation. Like other natural polymers, sericin has exceptional properties including biodegradability, non-antigenicity, compatibility, high nutritional value, good tailoring ability and extraordinary binding capacity of various drugs for a wide range of clinical application. Layered double hydroxides (LDH) are well-known inorganic nanocarriers for different proteins, enzymes, deoxyribonucleotides, viruses, pesticides, drugs, and dyes. In this study, we propose for the first time up to our knowledge, SS-LDH nanohybrids for the delivery of PMX. Firstly, MgAl-Cl-LDH were synthesized by the co-precipitation method followed by subsequent hydrothermal treatment.
Secondly, the anionic PMX drug was loaded (intercalated) into LDH brucite layers through the anion exchange method.
Thirdly, LDH-PMX was modified (entrapped) with sericin protein via the desolvation technique this led to enhancement of serum stability and hemocompatibility of LDH, also the rapid release of the highly hydrophilic PMX was hindered to some extent. Finally, our synthesized APTES-ZnO QDs were covalently conjugated to the carboxylic groups to Seri@LDH-PMX through an amide bond imparting a diagnostic value to our developed nanohybrids thus enabling tumor tissues imaging ensuring the localization of NPs in the tumor.
The optimal formulation, APTES-ZnO QDs/ Seri@LDH2-PMX (GTA); (F7) (201.9±2.3 nm, -21.1±0.51 mV) exhibited an irregular (modified-hexagonal) shape.
PMX intercalation efficiency was 90.7 %. Complete physicochemical characterization of the prepared nanohybrids was performed via determination of the drug content, particle size, zeta potential, XRD, TEM, DSC and FT-IR, photoluminescence emission.
DSC of the optimal formulation showed the disappearance of the characteristic endothermal peaks of PMX also showed shift of one of the endothermic peaks of sericin with the disappearance of other peaks, as an indication of the change in sericin and PMX decomposition temperatures in F7. FT-IR spectrum of the optimal formula confirmed the incorporation of PMX in nanohybrids and the effective sericin modification. XRD revealed the amorphous nature of F7 due to sericin modification. Furthermore, the optimal formulation can emit fluorescence in the visible region of light upon excitation with certain wavelength confirming its capability for theragnostic applications.Solidification of the prepared nanohybrids was successfully achieved by freeze-drying that maintained their physicochemical characteristics.
Preferable enhanced and sustained release profiles from our fabricated nanohybrids were successfully achieved.
The optimal formulation was physically stable for three months with no significant changes in their size and zeta potential. For the evaluation of the anti-tumor efficacy of nanohybrids, the in vitro cytotoxicity studies of the free PMX and the optimized formulation were examined using MTT assay.
The in vitro cytotoxicity study on MDA-MB-231 breast cancer cells confirmed the potential of our prepared nanohybrids to significantly enhance the anti-tumor activity compared with free PMX drug.
Our prepared nanohybrids showed good in vitro serum stability without any aggregation observed in serum up to 6 h and accepted hemocompatibility.
Cellular uptake study revealed the effective uptake of F7 by MDA-MB-231 breast cancer cells also flow cytometry study confirmed the cellular uptake quantitively