Photoinduced Endosomal Escape Mechanism: A View from Photochemical Internalization Mediated by CPP-Photosensitizer Conjugates.

Photoinduced Endosomal Escape Mechanism: A View from Photochemical Internalization Mediated by CPP-Photosensitizer Conjugates.
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DOI:
10.3390/molecules26010036
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发表时间:
2020-12-23
期刊:
Molecules (Basel, Switzerland)
影响因子:
--
通讯作者:
Ohtsuki T
Ohtsuki T
中科院分区:
其他
文献类型:
--
作者:
Soe TH;Watanabe K;Ohtsuki T

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基于细胞穿透肽(CPP)的药物/大分子递送系统中的内体逃逸通常是不足的。CPP融合的分子倾向于保持被捕获在内体内,并且最终被降解而不是被递送到胞质溶胶中。用于CPP融合分子的内体逃逸的方法之一是光化学内化(PCI),其基于光和光敏剂的使用并且依赖于光诱导的内体膜去稳定化以释放货物分子。目前,尚不清楚这种递送策略在光刺激后如何表现。最近的发现,包括我们的研究使用CPP-货物-光敏剂缀合物,揭示了光诱导的内体逃逸机制。本文综述了CPP-光敏剂和CPP-货物-光敏剂偶联物的结构设计及其应用的PCI机制。
Endosomal escape in cell-penetrating peptide (CPP)-based drug/macromolecule delivery systems is frequently insufficient. The CPP-fused molecules tend to remain trapped inside endosomes and end up being degraded rather than delivered into the cytosol. One of the methods for endosomal escape of CPP-fused molecules is photochemical internalization (PCI), which is based on the use of light and a photosensitizer and relies on photoinduced endosomal membrane destabilization to release the cargo molecule. Currently, it remains unclear how this delivery strategy behaves after photostimulation. Recent findings, including our studies using CPP-cargo-photosensitizer conjugates, have shed light on the photoinduced endosomal escape mechanism. In this review, we discuss the structural design of CPP-photosensitizer and CPP-cargo-photosensitizer conjugates, and the PCI mechanism underlying their application.
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