De Novo Design of Phototheranostic Sensitizers Based on Structure-Inherent Targeting for Enhanced Cancer Ablation
De Novo Design of Phototheranostic Sensitizers Based on Structure-Inherent Targeting for Enhanced Cancer Ablation
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DOI：
10.1021/jacs.8b09117
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发表时间：
2018-11-21
影响因子：
15
通讯作者：
Peng, Xiaojun
中科院分区：
文献类型：
--
作者：
Li, Mingle;Long, Saran;Peng, Xiaojun
结构固有靶向（SIT）药物对于临床精准医学尤为重要；然而，用于同步癌症诊断和靶向光动力治疗（PDT）的SIT光治疗仍然非常缺乏。在此，我们首次提出了一种“一劳永逸”的策略，利用福斯特共振能量转移（FRET）机制来构建这种万能的SIT光治疗学。值得注意的是，这种新颖的策略不仅可以赋予传统敏化剂高效的天然肿瘤靶向能力，还可以同时提高其光敏活性，从而显着提高治疗指数。静脉注射制备好的SIT治疗诊断剂后，肿瘤部位明显“变亮”，并与邻近组织区分开来，显示出高达12.5的近红外信号背景比值。更重要的是，受益于FRET效应，光捕获能力和102产量显着增强。更好的是，还同时实现了其他有利的特征，包括特定的线粒体锚定、增强的细胞摄取（>13倍）以及理想的生物相容性，所有这些都可以使体外和体内的抗癌效率得到数量级的提升。我们相信这一一站式的SIT平台将为未来的癌症精准治疗提供新的思路。
Structure-inherent targeting (SIT) agents are of particular importance for clinical precision medicine; however, there still exists a great lack of SIT phototheranostics for simultaneous cancer diagnosis and targeted photodynamic therapy (PDT). Herein, for the first time, we propose a "one-for-all" strategy by using the Forster resonance energy transfer (FRET) mechanism to construct such omnipotent SIT phototheranostics. Of note, this novel tactic can not only endow conventional sensitizers with highly effective native tumor-targeting potency but also simultaneously improve their photosensitization activities, resulting in dramatically boosted therapeutic index. After intravenous injection of the prepared SIT theranostic, the neoplastic sites are distinctly "lighted up" and distinguished from neighboring tissues, showing a near-infrared signal-to-background ratio value as high as 12.5. More importantly, benefiting from the FRET effect, markedly amplified light harvesting ability and 102 production are demonstrated. Better still, other favorable features are also simultaneously achieved, including specific mitochondria anchoring, augmented cellular uptake (>13-fold), as well as ideal biocompatibility, all of which allow orders-of-magnitude promotion in anticancer efficiency both in vitro and in vivo. We believe this one-for-all SIT platform will provide a new idea for future cancer precision therapy.