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

• Published in: Drug design, development and therapy Vol. 16; pp. 1963 - 1974
• Main Authors: Habibullah, Mahmoud M, Mohan, Syam, Syed, Nabeel Kashan, Makeen, Hafz A, Jamal, Qazi Mohammad Sajid, Alothaid, Hani, Bantun, Farkad, Alhazmi, Alaa, Hakamy, Ali, Kaabi, Yahia A, Samlan, Ghalia, Lohani, Mohtashim, Thangavel, Neelaveni, Al-Kasim, Mohamed Ahmed
• Format: Journal Article
• Language: English
• Published: Macclesfield Dove Medical Press Limited 01.01.2022; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: 3-D graphics; Analysis; anticancer potency; Anticancer properties; Antimitotic agents; Antineoplastic agents; Antineoplastic drugs; Antitumor agents; Binding; Biomarkers; Body fat; Breast cancer; Cancer; Cancer cells; Cancer therapies; Chemotherapy; Chitosan; Cytotoxicity; docking analysis; Doxorubicin; Drug carriers; Drug delivery; Drug delivery systems; Drugs; Epidermal growth factor; Estrogens; Growth hormones; Health aspects; Lipids; Molecular docking; Nanoparticles; Original Research; Peptides; Photon correlation spectroscopy; Polydispersity; Protein binding; Proteins; Receptors; Side effects; Somatotropin; Spectroscopy; Toxicity; Tumors; Vehicles; Zeta potential; Saudi Arabia
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S367586

Introduction: 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. Objective: 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. Methods: 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. Results: 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. Conclusion: 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. Keywords: anticancer potency, nanoparticles, cytotoxicity, docking analysis