Lin Kai, Ma Zhao, Li Jin, Tang Menghuan, Lindstrom Aaron, Ramachandran Mythili, Zhu Shaoming, Lin Tzu-Yin, Zhang Lanwei, Li Yuanpei
Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA.
Department of Urology and Pathology, New York University School of Medicine, New York, NY 10016, USA.
Adv Funct Mater. 2021 Mar 3;31(10). doi: 10.1002/adfm.202008460. Epub 2020 Dec 16.
Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but its therapeutic effects are limited by the nonselective subcellular localization and poor intratumoral retention of small-molecule photosensitizes. Here a fiber-forming nanophotosensitizer (PQC NF) that is composed of mitochondria targeting small molecules of amphiphilicity is reported. Harnessing the specific mitochondria targeting, the light-activated PQC NFs produce approximately 110-fold higher amount of reactive oxygen species (ROS) in cells than free photosensitizers and can dramatically induce mitochondrial disruption to trigger intense apoptosis, showing 20-50 times better anticancer potency than traditional photosensitizers. As fiber-shaped nanomaterials, PQC NFs also demonstrated a long-term retention in tumor sites, solving the challenge of rapid clearance of small-molecule photosensitizers from tumors. With these advantages, PQC NFs achieve a 100% complete cure rate in both subcutaneous and orthotopic oral cancer models with the administration of only a single dose. This type of single small molecule-assembled mitochondria targeting nanofibers offer an advantageous strategy to improve the therapeutic effects of conventional PDT.
光动力疗法（PDT）已成为癌症治疗中一种有吸引力的替代方法，但其治疗效果受到小分子光敏剂非选择性亚细胞定位和肿瘤内滞留性差的限制。本文报道了一种由靶向线粒体的两亲性小分子组成的纤维状纳米光敏剂（PQC NF）。利用特定的线粒体靶向作用，光激活的PQC NFs在细胞中产生的活性氧（ROS）量比游离光敏剂高出约110倍，并能显著诱导线粒体破坏以引发强烈的细胞凋亡，抗癌效力比传统光敏剂高20至50倍。作为纤维状纳米材料，PQC NFs在肿瘤部位也表现出长期滞留，解决了小分子光敏剂从肿瘤中快速清除的难题。凭借这些优势，在皮下和原位口腔癌模型中，仅单次给药PQC NFs就能实现100%的完全治愈率。这种由单个小分子组装而成的靶向线粒体的纳米纤维为提高传统光动力疗法的治疗效果提供了一种有利策略。
