Abstract Stimulus-sensitive nanoparticles (NPs) have been established to widely adapt to remarkable abnormalities under the tumor microenvironment, which can observably enhance the therapeutic efficiency, improve the specific targeting ability and reduce the side effects. Photodynamic therapy (PDT) as a promising non-invasive and selective treatment for cancers through photodynamic reaction can profit from stimulus-sensitive NPs. Herein, a harmonious amphiphilic polymer (PEG-b-PTPPDS-b-PEG) with an extremely sensitive redox response is constructed via click chemistry between N3-TPPC6-N3, PEG-N3 and alkynyl-containing disulfide ester for PDT. This polymer can be self-assembled into micelles with excellent stability, ultra-fast sensitivity of redox-triggered porphyrin release, and significant photodynamic anticancer performance. The redox-triggered dissociation of micelles and the release of porphyrin are much faster than common porphyrin-containing polymer. The bio-distribution and phototoxicity of micelles against A549 cells are measured and evaluated in vitro by flow cytometry, confocal scanning laser microscopy (CLSM) and MTT assay, respectively. The results reveal that PEG-b-PTPPDS-b-PEG micelles can effectively enhance the cellular uptake and cellular internalization of porphyrin and have an extremely low dark toxicity with efficient PDT towards A549 cells. This intracellular responsive nanoparticle provides a potential strategy for anticancer therapeutic application.

中文翻译：

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用于增强光动力疗法的超灵敏氧化还原响应卟啉基聚合物纳米颗粒

摘要 刺激敏感纳米颗粒（NPs）被广泛应用于肿瘤微环境下的显着异常，可显着提高治疗效率，提高特异性靶向能力，减少副作用。光动力疗法 (PDT) 作为一种有前途的非侵入性和选择性癌症治疗方法，通过光动力反应可以从刺激敏感的 NPs 中获益。在此，通过 N3-TPPC6-N3、PEG-N3 和用于 PDT 的含炔基二硫酯之间的点击化学构建了一种具有极其敏感氧化还原反应的和谐两亲聚合物（PEG-b-PTPPDS-b-PEG）。这种聚合物可以自组装成胶束，具有优异的稳定性、氧化还原引发的卟啉释放的超快灵敏度和显着的光动力抗癌性能。氧化还原引发的胶束解离和卟啉的释放比普通的含卟啉聚合物快得多。分别通过流式细胞术、共聚焦扫描激光显微镜 (CLSM) 和 MTT 测定法在体外测量和评估胶束对 A549 细胞的生物分布和光毒性。结果表明，PEG-b-PTPPDS-b-PEG胶束可有效增强卟啉的细胞摄取和细胞内化，并且对A549细胞具有极低的暗毒性和有效的PDT。这种细胞内响应纳米颗粒为抗癌治疗应用提供了一种潜在的策略。分别通过流式细胞术、共聚焦扫描激光显微镜 (CLSM) 和 MTT 测定法在体外测量和评估胶束对 A549 细胞的生物分布和光毒性。结果表明，PEG-b-PTPPDS-b-PEG胶束可有效增强卟啉的细胞摄取和细胞内化，并且对A549细胞具有极低的暗毒性和有效的PDT。这种细胞内响应纳米颗粒为抗癌治疗应用提供了一种潜在的策略。分别通过流式细胞术、共聚焦扫描激光显微镜 (CLSM) 和 MTT 测定法在体外测量和评估胶束对 A549 细胞的生物分布和光毒性。结果表明，PEG-b-PTPPDS-b-PEG胶束可有效增强卟啉的细胞摄取和细胞内化，并且对A549细胞具有极低的暗毒性和有效的PDT。这种细胞内响应纳米颗粒为抗癌治疗应用提供了一种潜在的策略。