Activatable photothermal agents with target-initiated large spectral separation for highly effective reduction of side effects.
Activatable photothermal agents with target-initiated large spectral separation for highly effective reduction of side effects.
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可激活光热剂，具有目标引发的大光谱分离，可高效减少副作用
DOI：
10.1039/d2sc02467e
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发表时间：
2022-08-24
期刊：
影响因子：
8.4
通讯作者：
中科院分区：
文献类型：
--
作者：
具有最小副作用的光热剂（PTA）是将癌症光热治疗（PTT）转化为临床应用的关键。然而，大多数目前可用的PTA缺乏真正的选择性激活，以减少副作用，因为光热剂和其相应的产品之间的严重光谱重叠。本研究报告了具有靶向启动的大光谱分离的可激活的PTA的构建，以高效地减少副作用。这种设计的探针涉及两种H2 O2可活化的PTA，aza-BOD-B1（单可活化位点）和aza-BOD-B2（多可活化位点）。与H2 O2作用后，aza-BOD-B1在750 ~ 810 nm范围内仅表现出轻微的吸收红移（60 nm），且光谱重叠严重，导致808 nm光照射时对正常组织产生轻微的光热效应。相比之下，aza-BOD-B2显示出从660 nm到810 nm的大吸收光谱分离（150 nm），实现了真正的选择性活化，以最大限度地减少癌症PTT期间的副作用。此外，体外和体内研究表明，aza-BOD-B2可以特异性地诱导癌细胞和肿瘤的光热消融，同时使正常部位不受损伤，而aza-BOD-B1对正常细胞表现出不期望的副作用。我们的研究为光疗的不良副作用问题提供了一个实用的解决方案，这是精准医学的一个进步。
Photothermal agents (PTAs) with minimized side effects are critical for transforming cancer photothermal therapy (PTT) into clinical applications. However, most currently available PTAs lack true selective activation to reduce side effects because of heavy spectral overlap between photothermal agents and their corresponding products. This study reports the construction of activatable PTAs with target-initiated large spectral separation for highly effective reduction of side effects. Such designed probes involve two H2O2-activatable PTAs, aza-BOD-B1 (single activatable site) and aza-BOD-B2 (multiple activatable site). After interacting with H2O2, aza-BOD-B1 only displays a mild absorption redshift (60 nm) from 750 nm to 810 nm with serious spectral overlap, resulting in a mild photothermal effect on normal tissues upon 808 nm light irradiation. In contrast, aza-BOD-B2 displays a large absorption spectral separation (150 nm) from 660 nm to 810 nm, achieving true selective activation to minimize side effects during PTT of cancer. Besides, in vitro and in vivo investigations demonstrated that aza-BOD-B2 can specifically induce photothermal ablation of cancer cells and tumors while leaving normal sites undamaged, whereas aza-BOD-B1 exhibits undesirable side effects on normal cells. Our study provides a practical solution to the problem of undesired side effects of phototherapy, an advance in precision medicine.
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