Synthesis and Characterization of Acacia-Stabilized Doxorubicin-Loaded Gold Nanoparticles for Breast Cancer Therapy

Abstract

The targeted delivery of drugs is vital in breast cancer treatment due to its ability to produce long-lasting therapeutic effects with minimal side effects. This study reports the successful development of doxorubicin hydrochloride (DOX)-loaded colloidal gold nanoparticles stabilized with acacia gum (AG). Optimization studies varied AG concentrations (0.25% to 3% w/v) to determine optimal conditions for nanoparticle synthesis. The resulting acacia stabilized gold nanoparticles (AGNPs) were characterized using various techniques including high-resolution transmission electron microscopy (HR-TEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), and selected area electron diffraction (SAED). In vitro drug release studies demonstrated a higher release rate of DOX in sodium acetate buffer (pH 5.0) compared to phosphate buffer saline (pH 7.4), suggesting an enhanced therapeutic efficacy in acidic tumor environments. Cytotoxicity of DOX-AGNPs and free DOX was assessed in human breast cancer cells (MDA-MB-231). The DOX-AGNPs exhibited significantly greater cytotoxicity, indicating enhanced efficacy in targeting cancer cells. This enhancement suggests that adsorbing DOX on the surface of gold nanoparticles can improve drug delivery and effectiveness, potentially reducing side effects compared to pure DOX and traditional delivery methods. Stability tests conducted over six months at 25±1°C showed significant changes in particle size and PDI, suggesting limited stability under these conditions. Overall, the acacia-stabilized gold nanoparticles synthesized in this study exhibit promising characteristics for drug delivery applications, particularly in cancer therapy, with effective drug loading, controlled release, and favorable physicochemical properties.

Keywords

green synthesis - gold nanoparticles - breast cancer - acacia gum - doxorubicin hydrochloride

• References

• 1 Siegel RL, Giaquinto AN, Jemal A. CA Cancer J Clin 2024; 74: 203
• 2 Ali-Thompson S, Daly GR, Dowling GP. et al. A bibliometric analysis of HER2-positive breast cancer: 1987–2024. Frontiers in Oncology 2024; 14
• 3 Gradishar WJ, Anderson BO, Balassanian R. et al. Breast cancer, version 4.2017, NCCN clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network 2018; 16: 310-320
• 4 Sahu A, Das PK, Meher S. Recent advancements in machine learning and deep learning-based breast cancer detection using mammograms. Physica Medica 2023; 114: 103138
• 5 Zhang N, Xiong G, Liu Z. Toxicity of metal-based nanoparticles: Challenges in the nano era. Front Bioeng Biotechnol 2022; 10: 1001572
• 6 Soliman SS, Alhamidi TB, Abdin S. et al. Effective targeting of breast cancer cells (MCF7) via novel biogenic synthesis of gold nanoparticles using cancer-derived metabolites. PloS one 2020; 15: e0240156
• 7 Pooja D, Panyaram S, Kulhari H. et al. Xanthan gum stabilized gold nanoparticles: characterization, biocompatibility, stability and cytotoxicity. Carbohydr Polym 2014; 110: 1-9
• 8 Thipe VC, Jatar A, Raphael Karikachery A. et al. Green Nanotechnology of Yucca filamentosa- Phytochemicals-Functionalized Gold Nanoparticles-Antitumor Efficacy Against Prostate and Breast Cancers. Nanotechnol Sci Appl 2023; 16: 19-40
• 9 Rivankar S. An overview of doxorubicin formulations in cancer therapy. J Cancer Res Ther 2014; 10: 853-858
• 10 Yang F, Kemp CJ, Henikoff S. Doxorubicin enhances nucleosome turnover around promoters. Curr Biol 2013; 23: 782-787
• 11 Kim JE, Cho HJ, Kim JS. et al. The limited intestinal absorption via paracellular pathway is responsible for the low oral bioavailability of doxorubicin. Xenobiotica 2013; 43: 579-591
• 12 Zeleke G, Dejene T, Tadesse W. et al. Gum Arabic Production and Population Status of Senegalia senegal (L.) Britton in Dryland Forests in South Omo Zone, Ethiopia. Sustainability 2021; 13: 11671
• 13 Al-Jubori Y, Ahmed NTB, Albusaidi R. et al. The Efficacy of Gum Arabic in Managing Diseases: A Systematic Review of Evidence-Based Clinical Trials. Biomolecules 2023; 13: 138
• 14 Aphibanthammakit C, Barbar R, Nigen M. et al. Emulsifying properties of Acacia senegal gum: Impact of high molar mass protein-rich AGPs. Food Chem X 2020; 6: 100090
• 15 Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int J Mol Sci 2020; 21: 3233
• 16 Devi L, Gupta R, Jain SK. et al. Synthesis, characterization and in vitro assessment of colloidal gold nanoparticles of Gemcitabine with natural polysaccharides for treatment of breast cancer. J Drug Deliv Technol 2020; 56: 101565
• 17 Pooja D, Panyaram S, Kulhari H. et al. Natural polysaccharide functionalized gold nanoparticles as biocompatible drug delivery carrier. Int J Biol. Macromol 2015; 80: 48-56
• 18 Foudah AI, Alam A, Salkini MA. et al. Synergistic Combination of Letrozole and Berberine in Ascorbic Acid-Stabilized AuNPs: A Promising Solution for Breast Cancer. Pharmaceuticals. 2023; 16: 1099
• 19 El-Ghareb WI, Swidan MM, Ibrahim IT. et al. ^99mTc-doxorubicin-loaded gallic acid-gold nanoparticles (^99mTc-DOX-loaded GA-Au NPs) as a multifunctional theranostic agent. Int J Pharm 2020; 586: 119514
• 20 Ahmad N, Bhatnagar S, Saxena R. et al. Biosynthesis and characterization of gold nanoparticles: Kinetics, in vitro and in vivo study. Mater Sci Eng C Mater Biol Appl 2017; 78: 553-564
• 21 López-Miranda JL, Molina GA, Esparza R. et al. Green Synthesis of Homogeneous Gold Nanoparticles Using Sargassum spp. Extracts and Their Enhanced Catalytic Activity for Organic Dyes. Toxics 2021; 9: 280
• 22 Soliman MKY, Salem SS, Abu-Elghait M. et al. Biosynthesis of Silver and Gold Nanoparticles and Their Efficacy Towards Antibacterial, Antibiofilm, Cytotoxicity, and Antioxidant Activities. Appl Biochem Biotechnol 2023; 195: 1158-1183