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      Drug Design, Development and Therapy (submit here)

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      Human Growth Hormone Fragment 176–191 Peptide Enhances the Toxicity of Doxorubicin-Loaded Chitosan Nanoparticles Against MCF-7 Breast Cancer Cells


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          Numerous drugs with potent toxicity against cancer cells are available for treating malignancies, but therapeutic efficacies are limited due to their inefficient tumor targeting and deleterious effects on non-cancerous tissue. Therefore, two improvements are mandatory for improved chemotherapy 1) novel delivery techniques that can target cancer cells to deliver anticancer drugs and 2) methods to specifically enhance drug efficacy within tumors. The loading of inert drug carriers with anticancer agents and peptides which are able to bind (target) tumor-related proteins to enhance tumor drug accumulation and local cytotoxicity is a most promising approach.


          To evaluate the anticancer efficacy of Chitosan nanoparticles loaded with human growth hormone hGH fragment 176–191 peptide plus the clinical chemotherapeutic doxorubicin in comparison with Chitosan loaded with doxorubicin alone.


          Two sets of in silico experiments were performed using molecular docking simulations to determine the influence of hGH fragment 176–191 peptide on the anticancer efficacy of doxorubicin 1) the binding affinities of hGH fragment 176–191 peptide to the breast cancer receptors, 2) the effects of hGH fragment 176–191 peptide binding on doxorubicin binding to these same receptors. Further, the influence of hGH fragment 176–191 peptide on the anticancer efficacy of doxorubicin was validated using viability assay in Human MCF-7 breast cancer cells.


          In silico analysis suggested that addition of the hGH fragment to doxorubicin-loaded Chitosan nanoparticles can enhance doxorubicin binding to multiple breast cancer protein targets, while photon correlation spectroscopy revealed that the synthesized dual-loaded Chitosan nanoparticles possess clinically favorable particle size, polydispersity index, as well as zeta potential.


          These dual-loaded Chitosan nanoparticles demonstrated greater anti-proliferative activity against a breast cancer cell line (MCF-7) than doxorubicin-loaded Chitosan. This dual-loading strategy may enhance the anticancer potency of doxorubicin and reduce the clinical side effects associated with non-target tissue exposure.

          Most cited references43

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            UCSF Chimera--a visualization system for exploratory research and analysis.

            The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/. Copyright 2004 Wiley Periodicals, Inc.
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              AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility.

              We describe the testing and release of AutoDock4 and the accompanying graphical user interface AutoDockTools. AutoDock4 incorporates limited flexibility in the receptor. Several tests are reported here, including a redocking experiment with 188 diverse ligand-protein complexes and a cross-docking experiment using flexible sidechains in 87 HIV protease complexes. We also report its utility in analysis of covalently bound ligands, using both a grid-based docking method and a modification of the flexible sidechain technique. (c) 2009 Wiley Periodicals, Inc.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                27 June 2022
                : 16
                : 1963-1974
                [1 ]Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University , Jazan, Saudi Arabia
                [2 ]SMIRES for Consultation in Specialized Medical Laboratories, Jazan University , Jazan, Saudi Arabia
                [3 ]Substance Abuse and Toxicology Research Center, Jazan University , Jazan, Saudi Arabia
                [4 ]School of Health Science, University of Petroleum and Energy Studies , Dehradun, Uttarakhand, India
                [5 ]Pharmacy Practice Research Unit, Department of Clinical Pharmacy, Faculty of Pharmacy, Jazan University , Jazan, Saudi Arabia
                [6 ]Department of Health Informatics, College of Public Health and Health Informatics, Qassim University , Al Bukayriyah, Saudi Arabia
                [7 ]Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University , Al-Baha, Saudi Arabia
                [8 ]Department of Microbiology, Faculty of Medicine, Umm Al-Qura University , Makkah, Saudi Arabia
                [9 ]Respiratory Therapy Department, Faculty of Applied Medical Sciences, Jazan University , Jazan, Saudi Arabia
                [10 ]Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University , Riyadh, Saudi Arabia
                [11 ]Emergency Medical Services Department, Faculty of Applied Medical Sciences, Jazan University , Jazan, Saudi Arabia
                [12 ]Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jazan University , Jazan, Saudi Arabia
                Author notes
                Correspondence: Mahmoud M Habibullah, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University , Al Maarefah Road, Jazan, Saudi Arabia, Tel +966 556644205, Email mhabibullah@jazanu.edu.sa
                Author information
                © 2022 Habibullah et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                : 23 March 2022
                : 15 June 2022
                Page count
                Figures: 6, Tables: 6, References: 43, Pages: 12
                Funded by: the Deanship of Scientific Research, Jazan University, Jazan, Saudi Arabia;
                This research was funded by the Deanship of Scientific Research, Jazan University, Jazan, Saudi Arabia; grant number JUP8/318.
                Original Research

                Pharmacology & Pharmaceutical medicine
                anticancer potency,nanoparticles,cytotoxicity,docking analysis


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