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  3. Photodynamic gel-bombs enhance tumor penetration and downstream synergistic therapies

Photodynamic gel-bombs enhance tumor penetration and downstream synergistic therapies

  • Signal Transduct Target Ther. 2025 Mar 19;10(1):94. doi: 10.1038/s41392-025-02186-y.
Xiaole Bai # 1 2,  Fanliang Meng # 3,  Xuejiao Wang 2,  Linyun He 2 4,  Chao Fan 2 5,  Liangjie Tian 1,  Yangning Zhang 2,  Jiahao Pan 2,  Qun Wu 2,  Xiangrong Hao 2,  Ying Wang 2,  Bo-Feng Zhu 6 7,  Jun-Bing Fan 8,  Bin Cong 9 10
Affiliations

Affiliations

  • 1 Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, 510515, Guangzhou, P.R. China.
  • 2 Cancer Research Institute, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, P.R. China.
  • 3 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, P.R. China.
  • 4 Department of Breast Surgery, Zhujiang Hospital, Southern Medical University, 510282, Guangzhou, P.R. China.
  • 5 Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, 518101, Shenzhen, P.R. China.
  • 6 Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, 510515, Guangzhou, P.R. China. zhubofeng7372@126.com.
  • 7 Key Laboratory of Forensic Medicine in Shanxi Province, School of Forensic Medicine, Shanxi Medical University, 030600, Jinzhong, P.R. China. zhubofeng7372@126.com.
  • 8 Cancer Research Institute, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, P.R. China. fjb2012@mail.ipc.ac.cn.
  • 9 Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, 510515, Guangzhou, P.R. China. cong6406@hebmu.edu.cn.
  • 10 Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, 050017, Shijiazhuang, P.R. China. cong6406@hebmu.edu.cn.
  • # Contributed equally.
PMID: 40102383 DOI: 10.1038/s41392-025-02186-y
Abstract

Nanoparticle-based drug delivery system remains a significant challenge in the current treatment of solid tumors, primarily due to their limited penetration capabilities. Herein, we successfully engineer photodynamic gel-bombs (DCM@OPR) capable of penetrating deeply into tumor tissues utilizing the photodynamic-triggered explosive energy and receptor-mediated transcytosis, significantly enhancing the therapeutic efficacy of breast Cancer. The photodynamic gel-bombs were fabricated by loading powerful components of chlorin e6 and MnO2 nanoparticles, as well as Doxorubicin, into a crosslinked CA2+-gel. Upon exposure to laser irradiation, the obtained photodynamic gel-bombs are capable of generating explosive energy, resulting in their fragmentation into numerous nanofragments. The photodynamic-triggered explosive energy subsequently drives these nanofragments to deeply penetrate into tumor tissues through gap leakage among tumor cells. In addition, the photodynamic-triggered explosive energy also promotes the escape of those therapeutic components (including chlorin e6, MnO2 nanoparticles, and doxorubicin) and nanofragments from lysosomes. In the subsequent stages, these nanofragments also exhibit excellent transcytosis capacity, facilitating deep penetration into tumor tissues. As expected, the enhanced penetration and accumulation of therapeutic components into tumor tissues can be achieved, significantly enhancing the anti-proliferation capacity against breast Cancer.

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