Bai Xiaole, Meng Fanliang, Wang Xuejiao, He Linyun, Fan Chao, Tian Liangjie, Zhang Yangning, Pan Jiahao, Wu Qun, Hao Xiangrong, Wang Ying, Zhu Bo-Feng, Fan Jun-Bing, Cong Bin
Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, 510515, Guangzhou, P.R. China.
Cancer Research Institute, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, 510515, Guangzhou, P.R. China.
Signal Transduct Target Ther. 2025 Mar 19;10(1):94. doi: 10.1038/s41392-025-02186-y.
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 MnO nanoparticles, as well as Doxorubicin, into a crosslinked Ca-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, MnO 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.
基于纳米颗粒的药物递送系统在当前实体瘤治疗中仍然是一项重大挑战，主要是因为它们的穿透能力有限。在此，我们成功构建了光动力凝胶炸弹（DCM@OPR），其能够利用光动力触发的爆炸性能量和受体介导的转胞吞作用深入渗透到肿瘤组织中，显著提高乳腺癌的治疗效果。光动力凝胶炸弹是通过将二氢卟吩e6和MnO纳米颗粒以及阿霉素的强效成分负载到交联的钙凝胶中制备而成。在激光照射下，所得到的光动力凝胶炸弹能够产生爆炸性能量，导致其破碎成众多纳米碎片。光动力触发的爆炸性能量随后驱动这些纳米碎片通过肿瘤细胞间的间隙渗漏深入渗透到肿瘤组织中。此外，光动力触发的爆炸性能量还促进这些治疗成分（包括二氢卟吩e6、MnO纳米颗粒和阿霉素）以及纳米碎片从溶酶体中逃逸。在随后的阶段，这些纳米碎片还表现出优异的转胞吞能力，有助于深入渗透到肿瘤组织中。正如预期的那样，可以实现治疗成分在肿瘤组织中的增强渗透和积累，显著提高对乳腺癌的抗增殖能力。
