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Adv. Healthc. Mater., Mar 03 2025, | https://doi.org/10.1002/adhm.202404819
Dual-Functional Hafnium Oxide Nanoplatform Combining High-Z Radiosensitization With Bcl-2 Gene Silencing for Enhanced Cancer Radiotherapy
Seungyong Shin 1, Ga-Hyun Bae 2, Jun-Hyeok Han 1, Ha Eun Shin 1, Joo Dong Park 1, Seunghyo Ko 1, Eun-Young Koh 2, Jieun Han 1, Su Chul Han 3, Jason Joon Bock Lee 3, Dong-Hyun Kim 4,5,6,7, Heerim Nam 3, Wooram Park 1,2
1Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea.
2Department of MetaBioHealth, Institute for Cross-disciplinary Studies (ICS), SKKU, Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea.
3Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Saemunan-ro 29, Seoul, 03181, Republic of Korea.
4Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, 60611, USA.
5Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
6Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, 60208, USA.
7Department of Biomedical Engineering, University of Illinois, Chicago, IL, 60607, USA.
S.S. and G.-H.B. contributed equally to this work as co-first authors.
Corresponding Author : Wooram Park
1Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University (SKKU), Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea.
2Department of MetaBioHealth, Institute for Cross-disciplinary Studies (ICS), SKKU, Seobu-ro 2066, Suwon, Gyeonggi, 16419, Republic of Korea.
3Department of Radiation Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Saemunan-ro 29, Seoul, 03181, Republic of Korea.
4Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, 60611, USA.
5Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, 60611, USA.
6Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL, 60208, USA.
7Department of Biomedical Engineering, University of Illinois, Chicago, IL, 60607, USA.
S.S. and G.-H.B. contributed equally to this work as co-first authors.
Corresponding Author : Wooram Park
Abstract
The efficacy of radiotherapy is often limited by insufficient radiosensitization and tumor radioresistance. This study reports a dual-functional hafnium oxide nanoplatform that combines high-Z radiosensitization with Bcl-2 gene silencing for enhanced cancer radiotherapy. The nanoplatform is developed by surface modification of hafnium oxide nanoparticles with polyethyleneimine, enabling efficient siRNA delivery while maintaining inherent high-Z radiosensitizing properties. Comprehensive physicochemical characterization confirmed the successful surface modification and stable siRNA complexation. Upon radiation exposure, the nanoplatform enhanced reactive oxygen species generation and DNA damage while simultaneously delivering Bcl-2 siRNA to suppress radioresistance mechanisms. In vitro studies revealed significant enhancement of radiation-induced cell death through synergistic effects of high-Z radiosensitization and Bcl-2 silencing, evidenced by increased γ-H2AX expression and apoptotic cell population. In a murine colon cancer model, the nanoplatform achieved remarkable tumor growth inhibition (80%) when combined with radiotherapy while exhibiting favorable biocompatibility in major organs. Mechanistic studies confirmed effective Bcl-2 downregulation and enhanced DNA damage in tumor tissues, validating this dual-functional therapeutic approach. This study presents a promising strategy for improving radiotherapy outcomes through the simultaneous enhancement of radiosensitization and suppression of radioresistance, potentially advancing the field of cancer radiotherapy.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-05)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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