Zhang Shunhu, Yang Nailin, Sun Shumin, Zhao Haitao, Wang Wenxuan, Nie Jihu, Pei Zifan, He Weiwei, Zhang Lifen, Cheng Liang, Cheng Zhenping
State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials; Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application; Suzhou key Laboratory of Macromolecular Deign and Precision Synthesis; College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, PR China.
Acta Biomater. 2025 Jan 24;193:406-416. doi: 10.1016/j.actbio.2025.01.017. Epub 2025 Jan 10.
Tumor hypoxia is one of key challenges in deep tumor photodynamic therapy (PDT), and how to fix this issue is attracting ongoing concerns worldwide. This work demonstrates dually fluorinated unimolecular micelles with desirable and stable oxygen-carrying capacity, high cellular penetration, and integrative type I & II PDT for deep hypoxic tumors. Dually fluorinated star copolymers with fluorinated phthalocyanines as the core are prepared through photoinitiated electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization under irradiation with NIR LED light at room temperature, followed by assembly into unimolecular micelles. Perfluorocarbons (PFCs) are also introduced into the star polymers during the polymerization to further enhance and stabilize oxygen-carrying capacity, which is slightly affected by concentration-induced size transformation. PFCs assist unimolecular micelles with repelling mucin adsorption, which results in superior cellular uptake within 1 h and high effective accumulation rates in tumors of CT26 tumor-bearing mice within 24 h after systemic administration, and showing effective anti-tumor effects under the irradiation of NIR LED light. This work provides a new type of nano-photosensitizers for highly efficient hypoxic PDT. STATEMENT OF SIGNIFICANCE: One of the major challenges in improving the efficiency of photodynamic therapy (PDT) for deep tumors is how to address tumor hypoxia, which is receiving continued attention worldwide. However, most of the reported oxygen carriers combine with photosensitizers by physical means and the carriers have the risk of dissociating easily, which is not conducive to long-term and efficient PDT, resulting in poor therapeutic effect. This work demonstrates dually fluorinated unimolecular micelles with desirable and stable oxygen-carrying capacity, high cellular penetration, and integrative type I & II PDT for enhanced deep hypoxic tumors, overcoming the key challenges of tumor hypoxia and low photosensitizer efficiency.
肿瘤缺氧是深部肿瘤光动力疗法（PDT）面临的关键挑战之一，如何解决这一问题正受到全球持续关注。这项工作展示了具有理想且稳定的载氧能力、高细胞穿透性以及用于深部缺氧肿瘤的I型和II型联合光动力疗法的双氟化单分子胶束。以氟化酞菁为核心的双氟化星形共聚物通过光引发电子/能量转移-可逆加成-断裂链转移（PET-RAFT）聚合在室温下用近红外发光二极管（NIR LED）光照制备，随后组装成单分子胶束。在聚合过程中还将全氟化碳（PFCs）引入星形聚合物中，以进一步增强和稳定载氧能力，其受浓度诱导的尺寸转变影响较小。PFCs有助于单分子胶束排斥粘蛋白吸附，这导致在全身给药后1小时内具有优异的细胞摄取能力，以及在24小时内在CT26荷瘤小鼠肿瘤中具有高有效积累率，并在NIR LED光照下显示出有效的抗肿瘤作用。这项工作为高效缺氧光动力疗法提供了一种新型的纳米光敏剂。意义声明：提高深部肿瘤光动力疗法（PDT）效率的主要挑战之一是如何解决肿瘤缺氧问题，这在全球范围内持续受到关注。然而，大多数报道的氧载体通过物理手段与光敏剂结合，且载体存在容易解离的风险，这不利于长期高效的光动力疗法，导致治疗效果不佳。这项工作展示了具有理想且稳定的载氧能力、高细胞穿透性以及用于增强深部缺氧肿瘤的I型和II型联合光动力疗法的双氟化单分子胶束，克服了肿瘤缺氧和光敏剂效率低的关键挑战。
