School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China.
Department of Comparative Medicine Laboratory Animal Center, Dalian Medical University, Dalian, 116000, China.
Adv Healthc Mater. 2023 Sep;12(23):e2300481. doi: 10.1002/adhm.202300481. Epub 2023 Apr 27.
Photodynamic therapy and sonodynamic therapy are two highly promising modalities for cancer treatment. The latter holds an additional advantage in deep-tumor therapy owing to the deep penetration of the ultrasonic radiation. The therapeutic efficacy depends highly on the photo/ultrasound-responsive properties of the sensitizers as well as their tumor-localization property and pharmacokinetics. A novel nanosensitizer system based on a polymeric phthalocyanine (pPC-TK) is reported herein in which the phthalocyanine units are connected with cleavable thioketal linkers. Such polymer could self-assemble in water forming nanoparticles with a hydrodynamic diameter of 48 nm. The degradable and flexible thioketal linkers could effectively inhibit the π-π stacking of the phthalocyanine units, rendering the resulting nanoparticles an efficient generator of reactive oxygen species upon light or ultrasonic irradiation. The nanosensitizer could be internalized into cancer cells readily, inducing cell death by efficient photodynamic and sonodynamic effects. The potency is significantly higher than that of the monomeric phthalocyanine (PC-4COOH). The nanosensitizer could also effectively inhibit the growth of tumor in liver tumor-bearing mice by these two therapies without causing noticeable side effects. More importantly, it could also retard the growth of a deep-located orthotopic liver tumor in vivo by sonodynamic therapy.
光动力疗法和声动力疗法是两种极具前途的癌症治疗方法。后者由于超声辐射的深穿透性，在深部肿瘤治疗中具有额外的优势。治疗效果高度依赖于光敏剂的光/超声响应特性以及它们的肿瘤定位特性和药代动力学。本文报道了一种基于聚合物酞菁（pPC-TK）的新型纳米敏化剂系统，其中酞菁单元通过可裂解的硫代缩醛连接体连接。这种聚合物在水中自组装形成纳米颗粒，水动力直径为 48nm。可降解的柔性硫代缩醛连接体可以有效地抑制酞菁单元的π-π堆积，使所得纳米颗粒在光或超声照射下有效地生成活性氧物种。纳米敏化剂可以很容易地被癌细胞内化，通过有效的光动力和声动力效应诱导细胞死亡。其效力明显高于单体酞菁（PC-4COOH）。该纳米敏化剂还可以通过这两种疗法有效抑制荷肝癌小鼠肿瘤的生长，而不会引起明显的副作用。更重要的是，它还可以通过声动力疗法延迟体内原位深部肝肿瘤的生长。
