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-to-volume 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 asan 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 bysubsequent hydrothermal treatment.
Secondly, theanionic 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 releaseof the highly hydrophilic PMX was hinderedto some extent.
Finally, our synthesized APTES-ZnO QDs were covalently conjugated to the carboxylic groups to Seri@LDH-PMX through an amide bondimparting a diagnostic value to our developed 122 nanohybrids thus enabling tumor tissuesimaging 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 efficiencywas90.7 %. 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, photoluminescenceemission.
DSCof the optimal formulation showed the disappearance of the characteristic endothermal peaks of PMX also show edshift of one of the endothermic peaksof sericin with the disappearance of other peaks, as an indication of the change in sericin and PMX decomposition temperaturesin F7.
FT-IR spectrumof the optimal formulacon firmed the incorporation of PMXin nanohybrids and the effective sericin modification.
XRD revealedthe amorphous nature of F7due to sericin modification. Furthermore, the optimal formulation can emit fluorescence in the visible region of light upon excitation with certain wave lengthconfirming 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 wasphysically 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 invitrocytotoxicity studies of the free PMXand the optimized formulation were examined using MTT assay. The invitro cytotoxicity study onMDA-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 invitro serum stability without anyaggregation observed in serum up to 6 h and accepted hemocompatibility.
Cellular uptake study revealed the effective uptake of F7byMDA-MB-231 breast cancer cellsalso flow cytometry study confirmed the cellular uptake quantitively.