Redox-sensitive iodinated polymersomes carrying histone deacetylase inhibitor as a dual-functional nano-radiosensitizer for enhanced radiotherapy of breast cancer
Open accessAbstract
Radiotherapy (RT) is a frequently used means in clinical tumor treatment. The outcome of RT varies, however, to a great extent, due to RT resistance or intolerable dose, which might be resolved by the development of radio-sensitizing strategies. Here, we report redox-sensitive iodinated polymersomes (RIP) carrying histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA, vorinostat), as a new dual-functional nano-radiosensitizer for breast cancer radiotherapy. SAHA-loaded RIP (RIP-SAHA) with a size of about 101 nm exhibited good colloidal stability while the reduction-activated release of SAHA, giving rise to better antitumor effect to 4T1 breast carcinoma cells than free SAHA. Accordingly, RIP-SAHA combined with a 4 Gy dose of X-ray radiation led to significantly enhanced suppression of 4T1 cells compared with SAHA combined 4 Gy of X-ray radiation, as a result of enhanced DNA damage and impeded DNA damage repair. The pharmacokinetics and biodistribution studies by single-photon emission computed tomography (SPECT) with 125I-labeled SAHA (125I-SAHA) showed a 17.3-fold longer circulation and 237.7-fold better tumor accumulation of RIP-SAHA over SAHA. The systemic administration of RIP-SAHA greatly sensitized radiotherapy of subcutaneous 4T1 breast tumors and brought about significant inhibition of tumor growth, without causing damages to major organs, compared with radiotherapy alone. RIP not only enhanced SAHA delivery but also acted as a radiosensitizer. RIP-SAHA emerges as a smart dual-functional nano-radiosensitizer to effectively enhance tumor radiotherapy.
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Therapeutic payload delivery, including chemotherapeutic agents, epigenetic modulators, and nucleic acid-based therapeutics, was commonly described in the included studies.
“Therapeutic payload delivery was also commonly described, including chemotherapeutic agents, epigenetic modulators, and nucleic acid-based therapeutics [27,42,45,52,71,72,73].”
From Nanoparticle-Mediated Radiosensitization in Breast Cancer: A Systematic Review of Preclinical Evidence and Translational Challenges (2026) · cites this paper as [71]
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- Authors
- Zhu, Z., Wu, M., Sun, J., Huangfu, Z., Yin, L., Yong, W., Sun, J., Wang, G., Meng, F., & Zhong, Z.
- Affiliations
- Soochow University (CN)
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, China
- Corresponding author
- Wang, Guanglin
- Zhong, Zhiyuan
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2021-01
- Volume
- 28
- Issue
- 1
- Pages
- 2301-2309
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- PMC
- PMC8567935
- OpenAlex
- W3210042510
- Cited by
- 17
- References
- 52
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 5
- FWCI
- 0.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Drug Delivery (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81720108024, 21976128)
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Natural Science Foundation of Jiangsu Province (BK20200100)
- China Postdoctoral Science Foundation (2016M591915, 2018T110547)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- histone deacetylase inhibitors, vorinostat, radiosensitizers, breast cancer radiotherapy, radiotherapy resistance, DNA repair, tissue distribution, tumor accumulation, SPECT imaging, drug delivery nanocarriers
- MeSH terms
- Vorinostat, Animals, Breast Neoplasms, Cell Survival, Chemistry, Pharmaceutical, DNA Damage, Drug Carriers, Female, Mice, Inbred BALB C, Oxidation-Reduction, Polymers, Radiation-Sensitizing Agents, Tissue Distribution, Cell Line, Tumor, Cell Proliferation, Mice, Nanoparticles, Histone Deacetylase Inhibitors, Drug Liberation
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