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Ahmed AH Abdellatif,1,2,* Fatma Ahmed,3,* Ahmed M Mohammed,2 Mansour Alsharidah,4 Amal Al-Subaiyel,1 Waad A Samman,5 Aisha A Alhaddad,5 Samiah Hamad Al-Mijalli,6 Mohammed A Amin,1,2 Hassan Barakat,7,8 Shaaban K Osman2,* 1Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim, 51452, Saudi Arabia; 2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt; 3Department of Zoology, Faculty of Science, Sohag University, Sohag, 82524, Egypt; 4Department of Physiology, College of Medicine, Qassim University, Buraydah, 51452, Saudi Arabia; 5Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, 42353, Saudi Arabia; 6Department of Biology, College of Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, 11671, Saudi Arabia; 7Department of Food Science and Human Nutrition, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, 51452, Saudi Arabia; 8Food Technology Department, Faculty of Agriculture, Benha University, Moshtohor, 13736, Egypt*These authors contributed equally to this workCorrespondence: Shaaban K Osman, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt, Tel +2 01129059936, Fax +2-088-312191, Email Shaabanosman@azhar.edu.eg Ahmed AH Abdellatif, Department of Pharmaceutics, College of Pharmacy, Qassim University, Qassim, 51452, Saudi Arabia, Email a.abdellatif@qu.edu.saAbstract: The real problem in pharmaceutical preparation is drugs’ poor aqueous solubility, low permeability through biological membranes, and short biological t1/2. Conventional drug delivery systems are not able to overcome these problems. However, cyclodextrins (CDs) and their derivatives can solve these challenges. This article aims to summarize and review the history, properties, and different applications of cyclodextrins, especially the ability of inclusion complex formation. It also refers to the effects of cyclodextrin on drug solubility, bioavailability, and stability. Moreover, it focuses on preparing and applying gold nanoparticles (AuNPs) as novel drug delivery systems. It also studies the uses and effects of cyclodextrins in this field as novel drug carriers and targeting devices. The system formulated from AuNPs linked with CD molecules combines the advantages of both CD and AuNPs. Cyclodextrins benefit in increasing aqueous drug solubility, loading capacity, stability, and size control of gold NPs. Also, AuNPs are applied as diagnostic and therapeutic agents because of their unique chemical properties. Plus, AuNPs possess several advantages such as ease of detection, targeted and selective drug delivery, greater surface area, high loading efficiency, and higher stability than microparticles. In the present article, we tried to present the potential pharmaceutical applications of CD-derived AuNPs in biomedical applications including antibacterial, anticancer, gene-drug delivery, and various targeted drug delivery applications. Also, the article highlighted the role of CDs in the preparation and improvement of catalytic enzymes, the formation of self-assembling molecular print boards, the fabrication of supramolecular functionalized electrodes, and biosensors formation.Keywords: AuNPs, nanotechnology, drug delivery, drug targeting, inclusion complexes, cancer management

Ahmed AH Abdellatif,1,2 Mahmoud A Younis,3 Mansour Alsharidah,4 Osamah Al Rugaie,5 Hesham M Tawfeek3 1Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia; 2Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt; 3Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt; 4Department of Physiology, College of Medicine, Qassim University, Buraydah, 51452, Saudi Arabia; 5Department of Basic Medical Sciences, College of Medicine and Medical Sciences, Qassim University, Unaizah, Al Qassim, 51911, Saudi ArabiaCorrespondence: Ahmed AH Abdellatif, Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia, Email a.abdellatif@qu.edu.sa Hesham M Tawfeek, Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt, Email heshamtawfeek@aun.edu.egAbstract: Despite the massive advancements in the nanomedicines and their associated research, their translation into clinically-applicable products is still below promises. The latter fact necessitates an in-depth evaluation of the current nanomedicines from a clinical perspective to cope with the challenges hampering their clinical potential. Quantum dots (QDs) are semiconductors-based nanomaterials with numerous biomedical applications such as drug delivery, live imaging, and medical diagnosis, in addition to other applications beyond medicine such as in solar cells. Nevertheless, the power of QDs is still underestimated in clinics. In the current article, we review the status of QDs in literature, their preparation, characterization, and biomedical applications. In addition, the market status and the ongoing clinical trials recruiting QDs are highlighted, with a special focus on the challenges limiting the clinical translation of QDs. Moreover, QDs are technically compared to other commercially-available substitutes. Eventually, we inspire the technical aspects that should be considered to improve the clinical fate of QDs.Graphical Abstract: Keywords: quantum dots, clinical translation, clinical trials, in vivo imaging, photodynamic therapy, biosensors

Background The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer’s onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications. Objective The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines. Methods The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11–7082. Results The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381–452 nm wherein the particles size ranged between 19.2±0.1 to 220.77±0.12 nm with the charge range −9.99±0.8 to −34.63±0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at >40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα. Conclusion This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.

Ahmed AH Abdellatif,1,2 Zafar Rasheed,3 Ahmad H Alhowail,4 Abdulmajeed Alqasoumi,5 Mansour Alsharidah,6 Riaz A Khan,7 Abdullah SM Aljohani,8 Maha A Aldubayan,4 Waleed Faisal9,10 1Department of Pharmaceutics, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt; 3Department of Medical Biochemistry, College of Medicine, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia; 4Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia; 5Department of Pharmacy Practice, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia; 6Department of Physiology, College of Medicine, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia; 7Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia; 8Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Qassim University, Buraydah, Kingdom of Saudi Arabia; 9School of Pharmacy, University College Cork, Cork, Ireland; 10Faculty of Pharmacy, Minya University, Minya, EgyptCorrespondence: Ahmed AH AbdellatifCollege of Pharmacy, Qassim University, Buraydah 51452, Kingdom of Saudi ArabiaEmail a.abdellatif@qu.edu.saBackground: The nuclear factor kappa-B (NF-κB) is a major transcription factor responsible for the production of numerous inflammatory mediators, including the tumor necrosis factor (TNFα), which has a lethal association with cancer’s onset. The silver nanoparticles (AgNPs) are widely used in cancer treatment and several other biomedical applications.Objective: The study aimed to determine the effects of silver citrate nanoparticles (AgNPs-CIT) on NF-κB activation together with TNFα mRNA/protein expressions in the phorbol myristate acetate (PMA)-stimulated MCF-7 human breast cancer cell-lines.Methods: The AgNPs-CIT were synthesized by the reduction method, and the prepared AgNPs-CIT were characterized for their shape, absorption in UV-VIS electromagnetic radiations, size distribution, ζ-potential, and antioxidant activity. The MCF-7 cell-lines were pretreated with AgNPs-CIT and stimulated with PMA. The TNFα mRNA expressions were determined by real-time PCR, whereas the protein production was determined by the ELISA. The NF-κB activity was distinctly observed by highly-specific DNA-based ELISA, and by NF-κB-specific inhibitor, Bay 11– 7082.Results: The prepared AgNPs-CIT were spherical and have an absorption wavelength range of 381– 452 nm wherein the particles size ranged between 19.2± 0.1 to 220.77± 0.12 nm with the charge range − 9.99± 0.8 to − 34.63± 0.1 mV. The prepared AgNPs-CIT showed comparative antioxidant activity at > 40% inhibitions level of the DPPH radicals. The AgNPs-CIT were found to be non-toxic to MCF-7 cell-lines and inhibited PMA-induced activation of the NF-κBp65, and also the mRNA/protein expression of TNFα.Conclusion: This is the first report that showed AgNPs-CIT inhibited TNFα expression via deactivation of the NF-κB signaling event in stimulated breast cancer cells. The results have important implications for the development of novel therapeutic strategies for the prevention/treatment of cancers and/or inflammatory disorders.Keywords: phorbol myristate acetate, PMA, TNFα, NF-κB, silver citrate nanoparticles, MCF-7 cell lines, cancer, inflammatory cytokines