Tehran University of Medical Sciences Frontiers in Biomedical Technologies 2345-5837 0 0 2025 10 28 1371 1371 Fatemeh Zare Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Zahra Masoumi Verki Department of Biomedical Engineering and Medical Physics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mina Nouri Department of Radiology Technology, School of Paramedical Sciences, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran Amirhossein Rashnoodi Department of Biomedical Engineering and Medical Physics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Emad Khoshdel Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran Başak Göksel Department of Medical Services and Techniques, Vocational School of Health Sciences, Istanbul Gelisim University, Istanbul, Turkey Fatemeh Ghamkhar-Nakhjiri Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Reza Malekzadeh Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2025 07 11 2025 10 03 Background: The aim of this study is to provide a comprehensive review of recent advances in the application of nanocarriers for targeted drug delivery and radiosensitization in cancer radiotherapy (RT), as well as to examine the challenges, solutions, and future prospects of this technology. Methods: A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Embase, identifying 373 records. Following PRISMA guidelines, 36 studies met inclusion criteria focusing on functionalized nanocarriers in cancer RT. Data extraction covered nanoparticle types, functionalization, therapeutic payloads, cancer models, radiation modalities, and outcomes. Results: Forty studies were analyzed, categorized into iron oxide-based (10), silver (10), bismuth-based (7), graphene-based (4), gadolinium-based (4), and titanium-based (2) nanoparticles (NPs). Bismuth-based NPs (BiNPs) showed superior radiosensitization with sensitizer enhancement ratios (SERs) of 1.25–1.48 and up to 450% reactive oxygen species (ROS) increase in vivo, achieving ~70% tumor volume reduction without systemic toxicity. Silver NPs (AgNPs) demonstrated dose enhancement factors (DEF) rising from 1.4 to 1.9 and synergistic effects with docetaxel plus 2 Gy radiation. Iron oxide NPs functionalized with HER2 and RGD ligands reduced cell viability by 1.95-fold and achieved DEF of 89.1 in targeted systems. Gadolinium NPs reached SERs up to 2.44 at 65 keV, while graphene-based systems enhanced ROS production by 75.2%. Titanium-based NPs increased ROS levels 2.5-fold. Combination therapies integrating chemotherapeutics such as cisplatin and curcumin with nanocarriers yielded SERs up to 4.29. Radiation modalities included megavoltage X-rays (4–10 MV, n=24), synchrotron keV X-rays (n=2), gamma rays (0.38–1.25 MeV, n=3), and electron beams (6–12 MeV, n=3). Conclusions: Bismuth-based NPs represent the most promising radiosensitizers due to their high efficacy, safety, and clinical relevance, supporting their advancement toward clinical translation. https://fbt.tums.ac.ir/index.php/fbt/article/view/1371 https://fbt.tums.ac.ir/index.php/fbt/article/download/1371/534