College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou, Zhejiang 310058, P. R. China.
Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang 310015, P. R. China.
Biomater Sci. 2024 Sep 25;12(19):4967-4979. doi: 10.1039/d4bm00847b.
Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer and has many characteristics including high metastatic rates, poor overall survival, and low response to traditional chemotherapy. Photodynamic therapy (PDT), emerging as a precise treatment modality, has shown promise in improving the antitumor response. However, it still faces challenges such as limited light penetration depth, rapid oxygen consumption, and inadequate targeting ability. In this study, we developed Rose Bengal (RB, photosensitizer) and oxygen co-loaded CREKA-modified UCNP-based nanoliposomes (CLIP-RB-PFOB@UCNP) for tumor targeting and near-infrared (NIR)-triggered deep and long-lasting PDT. Our results demonstrated that CLIP-RB-PFOB@UCNP effectively targeted and accumulated in tumor tissue through the interaction between CREKA and fibronectin, which is overexpressed in tumor cells. Under NIR irradiation, CLIP-RB-PFOB@UCNP exhibited significant destruction of orthotopic tumors, reduced the level of HIF-1α, and efficiently suppressed lung metastasis in a metastatic TNBC model. In conclusion, this study offers new avenues for improving the therapeutic outcomes of PDT for clinical TNBC treatment.
三阴性乳腺癌（TNBC）是一种侵袭性乳腺癌，具有许多特征，包括高转移率、整体生存率低以及对传统化疗反应不佳。光动力疗法（PDT）作为一种精准的治疗方式，在提高抗肿瘤反应方面显示出了前景。然而，它仍然面临着一些挑战，如有限的光穿透深度、快速的耗氧量和不足的靶向能力。在本研究中，我们开发了孟加拉玫瑰红（RB，光敏剂）和氧共载 CREKA 修饰的上转换纳米颗粒（CLIP-RB-PFOB@UCNP）纳米脂质体，用于肿瘤靶向和近红外（NIR）触发的深且持久的 PDT。我们的结果表明，CLIP-RB-PFOB@UCNP 通过 CREKA 与纤维连接蛋白的相互作用，有效靶向和聚集在肿瘤组织中，纤维连接蛋白在肿瘤细胞中过度表达。在近红外照射下，CLIP-RB-PFOB@UCNP 对原位肿瘤具有显著的破坏作用，降低了 HIF-1α 的水平，并在转移性 TNBC 模型中有效抑制了肺转移。总之，本研究为改善 PDT 治疗临床 TNBC 的疗效提供了新的途径。
