Good Steel Used in the Blade: Well-Tailored Type-I Photosensitizers with Aggregation-Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy.
Good Steel Used in the Blade: Well-Tailored Type-I Photosensitizers with Aggregation-Induced Emission Characteristics for Precise Nuclear Targeting Photodynamic Therapy.
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刀片用好钢：精心定制的具有聚集诱导发射特性的 I 型光敏剂，用于精确核靶向光动力治疗
DOI：
10.1002/advs.202100524
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发表时间：
2021-07
期刊：
影响因子：
--
通讯作者：
Tang BZ
中科院分区：
文献类型：
--
作者：
Kang M;Zhang Z;Xu W;Wen H;Zhu W;Wu Q;Wu H;Gong J;Wang Z;Wang D;Tang BZ
光动力学疗法（PDT）长期以来被认为是一种有前途的癌症治疗方法。然而，常规PDT的高氧依赖性显著损害了其整体治疗效果，特别是在缺氧实体瘤中。探索独特的PDT策略，包括高性能的低氧依赖性光敏剂（PS）和突出的药物递送系统是一个有吸引力但具有重大挑战性的任务。本文首次提出了基于具有聚集诱导发射（AIE）特性的I型PS的精确核靶向PDT方案。在两种合成的AIE PS中，TTFMN分别由于四苯乙烯和较小的单重态-三重态能隙的引入而表现出上级AIE性能和更强的I型活性氧（ROS）产生效率。借助溶酶体酸激活的达特-肽修饰的两亲性聚合物聚乳酸12 k-聚乙二醇5 k-琥珀酸酐修饰的达特，相应的TTFMN-负载纳米粒伴随酸触发的核靶向特性，可在肿瘤部位快速积聚，在核区有效产生I型ROS，在白色光照射下显著抑制肿瘤生长，全身毒性最小。这种微妙的“好钢用于刀刃”策略显著地最大化PDT功效，并为进一步转化医学中的优化癌症治疗提供了概念性而实用的范例。基于巧妙设计的具有聚集诱导发射特性的I型光敏剂的精确核靶向光动力学治疗（PDT）方案首次借助于溶酶体酸活化的达特修饰的核递送系统制造，其可以显著地最大化PDT功效。
Photodynamic therapy (PDT) has long been recognized to be a promising approach for cancer treatment. However, the high oxygen dependency of conventional PDT dramatically impairs its overall therapeutic efficacy, especially in hypoxic solid tumors. Exploration of distinctive PDT strategy involving both high‐performance less‐oxygen‐dependent photosensitizers (PSs) and prominent drug delivery system is an appealing yet significantly challenging task. Herein, a precise nuclear targeting PDT protocol based on type‐I PSs with aggregation‐induced emission (AIE) characteristics is fabricated for the first time. Of the two synthesized AIE PSs, TTFMN is demonstrated to exhibit superior AIE property and stronger type‐I reactive oxygen species (ROS) generation efficiency owing to the introduction of tetraphenylethylene and smaller singlet–triplet energy gap, respectively. With the aid of a lysosomal acid‐activated TAT‐peptide‐modified amphiphilic polymer poly(lactic acid)12k–poly(ethylene glycol)5k–succinic anhydride‐modified TAT, the corresponding TTFMN‐loaded nanoparticles accompanied with acid‐triggered nuclear targeting peculiarity can quickly accumulate in the tumor site, effectively generate type‐I ROS in the nuclear region and significantly suppress the tumor growth under white light irradiation with minimized systematic toxicity. This delicate “Good Steel Used in the Blade” tactic significantly maximizes the PDT efficacy and offers a conceptual while practical paradigm for optimized cancer treatment in further translational medicine. A precise nuclear targeting photodynamic therapy (PDT) protocol based on tactfully designed type‐I photosensitizers with aggregation‐induced emission characteristics is fabricated for the first time with the aid of a lysosomal acid‐activated TAT‐modified nuclear delivery system, which can significantly maximize the PDT efficacy.
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DOI：
10.3322/caac.20114
发表时间：
2011-07
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Agostinis P;Berg K;Cengel KA;Foster TH;Girotti AW;Gollnick SO;Hahn SM;Hamblin MR;Juzeniene A;Kessel D;Korbelik M;Moan J;Mroz P;Nowis D;Piette J;Wilson BC;Golab J
通讯作者：
Golab J
影响因子：
15
作者：
Jacobs, Aaron C.;Resendiz, Marino J. E.;Greenberg, Marc M.
通讯作者：
Greenberg, Marc M.
影响因子：
4.8
作者：
Garcia-Diaz, Maria;Huang, Ying-Ying;Hamblin, Michael R.
通讯作者：
Hamblin, Michael R.
影响因子：
15
作者：
Chowdhury, Goutam;Junnotula, Venkatraman;Gates, Kent S.
通讯作者：
Gates, Kent S.
影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Ward, Elizabeth
通讯作者：
Ward, Elizabeth