Green Synthesis of Silver Nanoparticles for Antimalarial Activity: Characterisation, Acute Toxicity, and Efficacy Studies in a Murine Model
Keywords:
Silver Nanoparticles (AgNPs), Green Synthesis, Antimalarial, Plasmodium berghei, Biopolymer Passivation, Nanomedicine, Mechanism of ActionAbstract
Recent studies highlight the therapeutic potential of green-synthesized silver nanoparticles (AgNPs), yet the precise mechanisms supporting their favourable safety profiles and biological efficacy remain underexplored, particularly concerning the role of their unique biopolymer matrix. We hypothesized that the extensive biopolymer passivation layer, inherent to green synthesis, is the critical determinant responsible for both the observed low toxicity and the enhanced antimalarial action of AgNPs. To test this, we synthesized AgNPs using a plant extract and performed comprehensive characterisation and in vivo antimalarial assessments. Our results confirmed the formation of spherical AgNPs with an optimal hydrodynamic size (43.04 nm). Crucially, multi-modal characterization (UV-Vis SPR red-shift at 431 nm, DLS/TEM size discrepancy, FTIR, EDX) converged to establish a thick, protective organic biopolymer matrix encapsulating the silver core, explaining the weak metallic signal in XRD. This unique structural feature directly correlated with an exceptionally favourable acute safety profile (LD50 > 5000 mg/kg), confirming the biopolymer's role in toxicity mitigation. Furthermore, these AgNPs demonstrated significant in vivo suppression of Plasmodium berghei parasitemia, primarily driven by a multifaceted mechanism: enhanced endocytic uptake into infected red blood cells (iRBCs) facilitated by the biopolymer coating, followed by targeted disruption of parasite heme detoxification, and induction of oxidative stress. This study reveals that the biopolymer matrix, a defining characteristic of green-synthesized AgNPs, is not merely a by-product but a key mechanistic modulator dictating both safety and antimalarial efficacy, providing critical insights for engineering biocompatible nanotherapeutics.
References
World Health Organization. World Malaria Report. Geneva: World Health Organization; 2023. Available from: https://www.who.int/teams/global-malaria-programme/malaria-reports/world-malaria-report-2023
Ikeh GO, Ugwu PE, Okpoto RC, Njoku EA, Diovu CC, Adonu CC. Biogenic Synthesis and Comparative Assessment of the Antimicrobial Activities of Silver and Zinc Nanoparticles of Dialium Guineense Leaf Extract Against Human Pathogens. J Complement Altern Med Res. 2024;25(12):211-26. https://doi.org/10.9734/jocamr/2024/v25i12607
Liu Z, Niu J, Niu C. Green synthesis of silver nanoparticles and their antimalarial activity. Int J Nanomedicine. 2019;14:4663-72. https://doi.org/10.2147/IJN.S209459
Rai M, Ingle AP, Paralikar P, Gupta I, Medici S, Santos CA. Recent advances in use of silver nanoparticles as antimalarial agents. Int J Pharm. 2017;526(1-2):254-70. https://doi.org/10.1016/j.ijpharm.2017.04.042
Gupta M, Seema K. Living Nano-factories: An Eco-friendly Approach Towards Medicine and Environment. In: Pal K, editor. Bio-manufactured Nanomaterials. Cham: Springer; 2021. p. 115-132. https://doi.org/10.1007/978-3-030-67223-2_6
Shayo GM, Elimbinzi E, Shao GN. Preparation methods, applications, toxicity and mechanisms of silver nanoparticles as bactericidal agent and superiority of green synthesis method. Heliyon. 2024;10(17):e36539. https://doi.org/10.1016/j.heliyon.2024.e36539
Alwhibi MS, Soliman DA, Awad MA, Alangery AB, Al Dehaish H, Alwasel YA. Green synthesis of silver nanoparticles: Characterization and its potential biomedical applications. Green Process Synth. 2021;10(1):412-20. https://doi.org/10.1515/gps-2021-0039
Anum F, Jabeen K, Javad S, Iqbal S, Tahir A, Javed Z, et al. Green synthesized silver nanoparticles as potent antifungal agent against Aspergillus terreus Thom. J Nanomater. 2021;2021:2992335. https://doi.org/10.1155/2021/2992335
Okorie NH, Ikeh GO, Adonu CC, Okorie CP, Omeh RC, Nwangwu AK. Precursor Chemistry and Antimicrobial Performance: A Green Synthesis Approach to the Zinc Oxide Nanoparticles. Asian J Appl Chem Res. 2025;16(2):116-40. https://doi.org/10.9734/ajacr/2025/v16i2333
Organisation for Economic Co-operation and Development. OECD Guideline for the Testing of Chemicals: Acute Oral Toxicity - Fixed Dose Procedure. Paris: OECD Publishing; 2020. Available from: https://www.oecd.org/en/publications/test-no-420-acute-oral-toxicity-fixed-dose-procedure_9789264070943-en.html
Salata OV. Applications of nanoparticles in biology and medicine. J Nanobiotechnology. 2004;2(1):3. https://doi.org/10.1186/1477-3155-2-3
Kora AJ, Rastogi L. Enhancement of antibacterial activity of capped silver nanoparticles in combination with antibiotics, on model gram-negative and gram-positive bacteria. Bioinorg Chem Appl. 2013;2013:871097. https://doi.org/10.1155/2013/871097
Jalab J, Abdelwahed W, Kitaz AM, Al-Kayali R. Green synthesis of silver nanoparticles using aqueous extract of Acacia cyanophylla and its antibacterial activity. Heliyon. 2021;7(9):e08033. https://doi.org/10.1016/j.heliyon.2021.e08033
Joshi P, Pandey L, Patel A, Baksh Z, Singh P, Singh R. Green Synthesis and Characterization of Silver Nanoparticles Using Stachytarpheta indica. Int J Curr Microbiol Appl Sci. 2025;14(4):163-72. https://doi.org/10.20546/ijcmas.2025.1404.004
Shahzadi S, Fatima S, ul ain Q, Shafiq Z, Janjua MRSA. A review on green synthesis of silver nanoparticles (SNPs) using plant extracts: a multifaceted approach in photocatalysis, environmental remediation, and biomedicine. RSC Adv. 2025;15(5):3858-903. https://doi.org/10.1039/D4RA07519F
Vanlalveni C, Lallianrawna S, Biswas A, Selvaraj M, Changmai B, Rokhum SL. Green synthesis of silver nanoparticles using plant extracts and their antimicrobial activities: a review of recent literature. RSC Adv. 2021;11(5):2804-37. https://doi.org/10.1039/D0RA09941D
Radulescu DM, Surdu VA, Ficai A, Ficai D, Grumezescu AM, Andronescu E. Green synthesis of metal and metal oxide nanoparticles: A review of the principles and biomedical applications. Int J Mol Sci. 2023;24(20):15397. https://doi.org/10.3390/ijms242015397
Kamaraj C, Balasubramani G, Siva C, Raja M, Balasubramanian V, Raja RK, et al. Ag nanoparticles synthesized using β-caryophyllene isolated from Murraya koenigii: Antimalarial (Plasmodium falciparum 3D7) and anticancer activity. J Clust Sci. 2017;28(4):1667-84. https://doi.org/10.1007/s10876-017-1180-6
Kojom Foko LP, Eya’ane Meva F, Eboumbou Moukoko CE, Ntoumba AA, Ngaha Njila MI, Belle Ebanda Kedi P, et al. A systematic review on anti-malarial drug discovery and antiplasmodial potential of green synthesis mediated metal nanoparticles. Malar J. 2019;18(1):337. https://doi.org/10.1186/s12936-019-2974-9
Tiwari S, Kumar R, Devi S, Sharma P, Chaudhary NR, Negi S, et al. Biogenically synthesized green silver nanoparticles exhibit antimalarial activity. Discov Nano. 2024;19(1):136. https://doi.org/10.1186/s11671-024-04098-2
Published on: 10-01-2025
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