Yang Chengli, Liao Xukun, Zhou Kai, Yao Yongchao, He Xinlong, Zhong Wen, Zheng Dan, Yang Yan, Li Ming, Zhou Meng, Zhou Yadi, Li Lin, Bai Yang, Shi Kun, Qian Zhiyong
Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, China.
Bioact Mater. 2025 Feb 12;48:1-17. doi: 10.1016/j.bioactmat.2025.02.014. eCollection 2025 Jun.
Breast cancer is the most prevalent and lethal malignancy among females, with a critical need for safer and less invasive treatments. Photodynamic therapy (PDT) can effectively eliminate tumor cells with minimal side effects. Furthermore, the combination of PDT and immunotherapy using nanoparticles has shown promise in treating both primary and distant metastatic tumor cells. Therefore, this study proposes applying the PDT-immunotherapy combination to breast cancer treatment. However, the low immunogenicity characteristic of "cold" tumors in part of breast cancer significantly diminishes therapeutic efficacy. To address this challenge, here, a nano-gel system (designated as HCSC-gel) is constructed, which co-delivers a mitochondria-targeted photosensitizer and a STING agonist, capable of robustly activating "cold" tumor immunity. This system is further enhanced by collagenase (CN) to improve therapeutic outcomes. Upon injection into the primary tumor site, HCSC-gel rapidly forms a gel matrix, releasing CN to degrade the tumor extracellular matrix and facilitate the penetration of photosensitizers, STING agonists, and oxygen into the tumor tissue. Under laser irradiation, PDT and STING-mediated immune responses are activated, reversing the low immunogenicity of breast cancer and effectively treating both primary and metastatic lesions. This HCSC-gel nano hydrogel delivery platform is anticipated to provide novel insights for the clinical management of breast cancer and other low immunogenic "cold" tumors, offering significant benefits to patients.
乳腺癌是女性中最常见且致命的恶性肿瘤,迫切需要更安全、侵入性更小的治疗方法。光动力疗法(PDT)能以最小的副作用有效消除肿瘤细胞。此外,使用纳米颗粒的PDT与免疫疗法相结合在治疗原发性和远处转移性肿瘤细胞方面已显示出前景。因此,本研究提出将PDT-免疫疗法联合应用于乳腺癌治疗。然而,部分乳腺癌中“冷”肿瘤的低免疫原性特征显著降低了治疗效果。为应对这一挑战,在此构建了一种纳米凝胶系统(命名为HCSC-凝胶),该系统共同递送一种线粒体靶向光敏剂和一种STING激动剂,能够强力激活“冷”肿瘤免疫。通过胶原酶(CN)进一步增强该系统以改善治疗效果。将HCSC-凝胶注射到原发性肿瘤部位后,它会迅速形成凝胶基质,释放CN以降解肿瘤细胞外基质,并促进光敏剂、STING激动剂和氧气渗透到肿瘤组织中。在激光照射下,激活PDT和STING介导的免疫反应,逆转乳腺癌的低免疫原性,有效治疗原发性和转移性病变。预计这种HCSC-凝胶纳米水凝胶递送平台将为乳腺癌和其他低免疫原性“冷”肿瘤的临床管理提供新的见解,为患者带来显著益处。
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