Single Small Molecule-Assembled Mitochondria Targeting Nanofibers for Enhanced Photodynamic Cancer Therapy In Vivo
Single Small Molecule-Assembled Mitochondria Targeting Nanofibers for Enhanced Photodynamic Cancer Therapy In Vivo
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DOI：
10.1002/adfm.202008460
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发表时间：
2020-12-16
影响因子：
19
通讯作者：
Li, Yuanpei
中科院分区：
文献类型：
--
作者：
Lin, Kai;Ma, Zhao;Li, Yuanpei
光动力疗法（Photodynamic Therapy，PDT）是一种新型的肿瘤治疗方法，但其治疗效果受到小分子光敏剂的非选择性亚细胞定位和肿瘤内滞留的限制。本文报道了一种由线粒体靶向两亲性小分子组成的纤维形成纳米光敏剂（PQC NF）。利用特异性线粒体靶向，光激活的PQC NF在细胞中产生比游离光敏剂高约110倍的活性氧，并且可以显著诱导线粒体破坏以引发强烈的细胞凋亡，显示出比传统光敏剂高20-50倍的体外抗癌效力。作为纤维状纳米材料，PQC NF还表现出在肿瘤部位的长期保留，解决了从肿瘤中快速清除小分子光敏剂的挑战。由于这些优点，PQC NF在皮下和原位口腔癌模型中仅施用单剂量就实现了100%的完全治愈率。这种类型的单个小分子组装的线粒体靶向纳米纤维提供了一种有利的策略，以改善常规PDT的体内治疗效果。
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 in cells than free photosensitizers and can dramatically induce mitochondrial disruption to trigger intense apoptosis, showing 20-50 times better in vitro 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 offers an advantageous strategy to improve the in vivo therapeutic effects of conventional PDT.