Targeted Radiosensitization in Cancer Radiotherapy Using Functionalized Nanocarriers: A Systematic Review

Fatemeh  Zare; Zahra  Masoumi-Verki; Mina  Nouri; Amirhossein   Rashnoodi; Emad  Khoshdel; Başak  Göksel; Fatemeh  Ghamkhar-Nakhjiri; Reza  Malekzadeh

doi:10.18502/fbt.v13i2.21950

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

DOI: https://doi.org/10.18502/fbt.v13i2.21950

Keywords: Nanocarrier; Targeted Drug Delivery; Radiosensitization; Cancer; Nanoparticle

Abstract

Purpose: This study aims 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 prospects of this technology.

Materials and Methods: This systematic review was conducted in accordance with PRISMA guidelines and protocol registered in PROSPERO (CRD420251154905). A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science, identifying 373 records. Following PRISMA guidelines, 40 studies met the 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 demonstrated superior radiosensitization with sensitizer enhancement ratios (SERs) of 1.25–1.48 and up to 450% increase in reactive oxygen species (ROS) in vivo, achieving ~70% tumor volume reduction without systemic toxicity. Silver NPs 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, including cisplatin and curcumin with nanocarriers, yielded SERs up to 4.29. The 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).

Conclusion: Bismuth-based NPs represent the most promising radiosensitizers due to their high efficacy, safety, and clinical relevance, supporting their advancement toward clinical translation.