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Guiding Appropriate Timing of Laser Irradiation by Polymeric Micelles for Maximizing Chemo-Photodynamic Therapy
International Journal of Nanomedicine ( IF 6.6 ) Pub Date : 2020-08-31 , DOI: 10.2147/ijn.s256477
Yun Zhu 1, 2 , Fangying Yu 1 , Yanan Tan 1, 3 , Lijuan Wen 1, 4 , Yinghong Li 5 , Hong Yuan 1 , Fuqiang Hu 1
Affiliation  

Background: Photoactivity “on-off” switchable nano-agents could shield phototoxicity until reaching target region, which immensely promoted photodynamic therapy. However, the masking ratio of nano-agents in vivo was dynamic and positively correlated with the phototoxicity induced by laser irradiation, in which case the timing of laser irradiation was unpredictable to maximize antitumor efficacy.
Methods: Herein, low molecular weight chitosan and hydrophobic polymethylacrylamide derivatives were linked via GSH cleavable 3, 3ʹ-dithiodipropionic acid to construct polymeric micelles (Ce6-CSPD). The doxorubicin loading nano-agent (Ce6-CSPD/DOX) could quench both photoactivity and fluorescence of photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) under physiological condition by homo-fluorescence resonance energy transfer (homoFRET).
Results: Once internalized by tumor cells, the photoactivity as well as fluorescence of Ce6 was recovered rapidly when motivated by intracellular high GSH. Specifically, the fluorescence intensity and photoactivity of Ce6 were proven to be positive linear correlated, upon which appropriate timing of laser irradiation could be determined by referring to the dynamic fluorescence intensity in vivo. In addition, the theranostic nano-agents also possessed the capacity of monitoring the DOX release process. Accordingly, under the guidance of fluorescence intensity, the experimental group subjected to laser irradiation at 18 h postadministration acquired the highest antitumor inhibition efficacy compared to that at four hours and 48 h, which held great potential for maximizing chemo-photodynamic therapy and avoiding nonspecific phototoxicity precisely to normal organs.
Conclusion: In summary, we prepared homoFRET-based theranostic nano-agent (Ce6-CSPD/DOX) for monitoring PDT precisely and decreasing phototoxicity to normal organs before reaching target region. Under the guidance of dynamic fluorescence intensity, the appropriate laser irradiation timing could be monitored to maximize antitumor therapy efficacy, which offered opportunities for monitoring efficiency of chemo-photodynamic therapy in a timely and accurate manner.



中文翻译:

指导聚合物胶束激光照射的适当时机最大化化学光动力治疗

背景:光活性“开-关”可切换纳米剂可以屏蔽光毒性直到到达目标区域,这极大地促进了光动力疗法。然而,体内纳米药物的掩蔽率是动态的,并且与激光照射诱导的光毒性呈正相关,在这种情况下,激光照射的时间是不可预测的,以最大限度地提高抗肿瘤功效。
方法:在此,低分子量壳聚糖和疏水性聚甲基丙烯酰胺衍生物通过 GSH 可裂解的 3, 3′-二硫代二丙酸连接以构建聚合物胶束 (Ce6-CSPD)。阿霉素负载纳米剂(Ce6-CSPD/DOX)可以通过同源荧光共振能量转移(homoFRET)在生理条件下猝灭光敏剂二氢卟酚e6(Ce6)和阿霉素(DOX)的光活性和荧光。
结果:一旦被肿瘤细胞内化,在细胞内高 GSH 的驱动下,Ce6 的光活性和荧光迅速恢复。具体而言,Ce6的荧光强度和光活性被证明是正线性相关的,在此基础上,可以通过参考体内动态荧光强度来确定激光照射的适当时机。此外,治疗诊断纳米剂还具有监测DOX释放过程的能力。因此,在荧光强度的指导下,与给药后4小时和48小时相比,激光照射的实验组在给药后18小时获得了最高的抗肿瘤抑制效果,
结论:综上所述,我们制备了基于homoFRET的治疗诊断纳米剂(Ce6-CSPD/DOX),用于精确监测PDT并在到达目标区域之前降低对正常器官的光毒性。在动态荧光强度的指导下,可以监测适当的激光照射时间,以最大限度地提高抗肿瘤治疗效果,这为及时、准确地监测化学光动力治疗的效率提供了机会。

更新日期:2020-08-31
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