Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control

Shiridokht, Fatemeh; Kehtari, Parniya; Eskandani, Morteza; Farajollahi, Alireza; Vandghanooni, Somayeh

doi:10.1016/j.ijpx.2025.100419

Cited by 7Radiation Therapy and DosimetryEffects of Radiation ExposureAdvanced Radiotherapy Techniques

Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control

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Shiridokht, Fatemeh, Kehtari, Parniya, Eskandani, Morteza, Farajollahi, Alireza, Vandghanooni, Somayeh·2025·International Journal of Pharmaceutics: X

DOI 10.1016/j.ijpx.2025.100419PMC PMC12581699

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Abstract

Cancer affects millions of individuals annually, with radiotherapy playing a crucial role in the treatment of over 70% of cases. Nevertheless, the effectiveness of radiotherapy is frequently limited by tumor radioresistance and the associated toxicity to normal tissues. Radiosensitizers enhance tumor sensitivity to ionizing radiation, optimizing doses and reducing damage. This review evaluates diverse radiosensitizers, including natural compounds (curcumin, resveratrol), chemotherapeutics (cisplatin, doxorubicin), and high-Z nanoparticles (gold, hafnium), which amplify DNA damage and ROS production. Advanced nanocarriers-carbon-, lipid-, and polymer-based-improve targeted delivery, specificity, and bioavailability. Various molecular mechanisms involving proteins such as p53, PARP1, miRNAs (miR-21, miR-155), and siRNAs are discussed in relation to their roles in modulating cell cycle progression, apoptosis, and gene expression to overcome resistance. Radioprotectors like antioxidants and amifostine safeguard normal tissues. Ongoing trials with hafnium oxide and cisplatin regimens show promise. Key findings highlight nanotechnology's role in enhancing radiosensitization via dose enhancement factors and synergistic therapies. Implications include personalized treatments tailored to tumor biology, the reduction of radioresistance through precision medicine and data-driven strategies, and ultimately, the improvement of radiotherapy efficacy and patient outcomes.

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Early studies predominantly focused on high-atomic-number materials, including gold, silver, gadolinium, and hafnium-based nanoparticles, with the primary objective of maximizing radiation energy deposition and secondary electron generation.
“Early studies predominantly focused on high-atomic-number (high-Z) materials, including gold, silver, gadolinium, and hafnium-based nanoparticles, with the primary objective of maximizing radiation energy deposition and secondary electron generation [9,85,95,96].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [96]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measured
Across included studies, nanoparticle-assisted radiotherapy was frequently associated with enhanced therapeutic activity compared with radiotherapy alone, including reduced cell viability, decreased clonogenic survival, increased apoptosis, enhanced DNA damage, delayed tumor growth, and in selected studies improved survival.
“Across the included studies, nanoparticle-assisted radiotherapy was frequently associated with enhanced therapeutic activity compared with radiotherapy alone, including reduced cell viability, decreased clonogenic survival, increased apoptosis, enhanced DNA damage, delayed tumor growth, and, in selected studies, improved survival outcomes [14,23,26,87,96,104,105].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [96]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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Clinical development of combinatorial nanoplatforms is challenged by issues related to reproducibility, manufacturing consistency, regulatory approval, scalability, and long-term safety.
“Although these combinatorial systems often demonstrate enhanced efficacy experimentally, their clinical development is challenged by issues related to reproducibility, manufacturing consistency, regulatory approval, scalability, and long-term safety [25,96,97].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [96]
The Conclusion and future perspective section identifies batch-to-batch inconsistency, production scalability, and limited long-term toxicity data as barriers to clinical translation. The Limitations of current radiosensitizer strategies section also calls for standardized manufacturing protocols. These passages support most of the claim, but our copy does not identify regulatory approval as a challenge. (LLM, conf=0.86)
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Authors: Shiridokht, F., Kehtari, P., Eskandani, M., Farajollahi, A., & Vandghanooni, S.
Affiliations: Tabriz University of Medical Sciences (IR)
Corresponding author: Vandghanooni, Somayeh
ORCID: Shiridokht, Fatemeh
Eskandani, Morteza
Farajollahi, Alireza
Vandghanooni, Somayeh
Venue: International Journal of Pharmaceutics: X
Publisher: Elsevier BV
Published: 2025-12
Volume: 10
Pages: 100419
ISSN: 2590-1567 (ISSN-L)
DOI: 10.1016/j.ijpx.2025.100419
PMC: PMC12581699
OpenAlex: W4415958691
Cited by: 4
References: 215
Citations by year: 2026: 4
FWCI: 0.70
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc/4.0/ (vor)
Locations: International Journal of Pharmaceutics X (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Funders: Tabriz University of Medical Sciences
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Physical Sciences › Physics and Astronomy › Radiation › Advanced Radiotherapy Techniques
Keywords: cancer radiotherapy, radiosensitizers, tumor radioresistance, nanocarriers, high-Z nanoparticles, gold nanoparticles, hafnium oxide nanoparticles, cisplatin, curcumin, resveratrol, reactive oxygen species, DNA damage, p53, PARP1, microRNA, siRNA, radiosensitization, radiotherapy toxicity, antioxidants, amifostine, targeted drug delivery, precision medicine

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Advancing cancer radiotherapy: Harnessing radiosensitizers and nanotechnology for enhanced tumor control

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