Christian K. Ngabdi, Raisha A. Fatiha, Jihan S. Azizah, Bayu Lestari, Nik A. N. N. Malek, Yanuar R. Fauzi, Shingo Nakahata, Muhammad Anshory, Holipah Holipah, Ayunda D. J. Putri, Happy K. Permatasari
Cancer is a leading cause of mortality worldwide due to uncontrolled proliferation, resistance to apoptosis, and metastasis. Chemotherapy and radiotherapy have improved survival, but the effectiveness is limited by toxicity and drug resistance. This condition has prompted the exploration of herbal medicines and nanotechnology-based alternatives. Green-synthesized silver nanoparticles (AgNPs), produced using phytochemical-rich plant extracts, are promising anticancer agents because of the eco-friendly synthesis, biocompatibility, and multitargeted effects. Therefore, this systematic review, following PRISMA 2020 guidelines, analyzed 26 in vitro studies published between 2015 and 2025 from PubMed, ScienceDirect, Taylor & Francis, Hindawi, and ProQuest. Evidence consistently showed selective cytotoxicity of green-synthesized AgNPs against cancer cells while sparing normal cells. Reported mechanisms included apoptosis induction through mitochondrial pathways, reactive oxygen species generation, cell cycle arrest, DNA damage, and inhibition of angiogenesis and metastasis. Smaller nanoparticles had higher potency, signifying the role of size and surface chemistry in therapeutic performance. In conclusion, green-synthesized AgNPs show considerable potential as novel anticancer nanomedicines. However, most evidence is limited to in vitro studies, with significant heterogeneity in synthesis methods. Standardized protocols, in vivo validation, and clinical examinations are required before clinical translation can be achieved. © 2025 Ngabdi et al.
Biomedical Science Master Program, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Centre for Sustainable Nanomaterials (CSNano), Ibnu Sina Institute for Scientific and Industrial Research, Universiti Teknologi Malaysia, Skudai, 81310, Malaysia; Department of Biochemistry and Biomolecular, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Division of HTLV-1/ATL Carcinogenesis and Therapeutics, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, 890-8544, Japan; Department of Dermatology, Erasmus MC, University Medical Center, Rotterdam, 3015 GD, Netherlands; Department of Public Health, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia