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Reconstructing the intracellular pH microenvironment for enhancing photodynamic therapy
Materials Horizons ( IF 12.2 ) Pub Date : 2020-01-13 , DOI: 10.1039/c9mh01824g Chaochao Wang 1, 2, 3, 4, 5 , Peiran Zhao 2, 5, 6, 7, 8 , Guoliang Yang 1, 2, 3, 4, 5 , Xiaoyan Chen 2, 5, 6, 7, 8 , Yaqin Jiang 2, 5, 6, 7, 8 , Xingwu Jiang 5, 9, 10, 11, 12 , Yelin Wu 5, 9, 10, 11, 12 , Yanyan Liu 2, 5, 6, 7, 8 , Weian Zhang 1, 2, 3, 4, 5 , Wenbo Bu 2, 5, 6, 7, 8
Materials Horizons ( IF 12.2 ) Pub Date : 2020-01-13 , DOI: 10.1039/c9mh01824g Chaochao Wang 1, 2, 3, 4, 5 , Peiran Zhao 2, 5, 6, 7, 8 , Guoliang Yang 1, 2, 3, 4, 5 , Xiaoyan Chen 2, 5, 6, 7, 8 , Yaqin Jiang 2, 5, 6, 7, 8 , Xingwu Jiang 5, 9, 10, 11, 12 , Yelin Wu 5, 9, 10, 11, 12 , Yanyan Liu 2, 5, 6, 7, 8 , Weian Zhang 1, 2, 3, 4, 5 , Wenbo Bu 2, 5, 6, 7, 8
Affiliation
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Acidic tumor microenvironments, characterized by weak acidity outside the cell (pH ∼ 6.5–7.0), have been revealed as a potential therapeutic target with specific acid-responsible materials. However, the intracellular pH of tumor cells is still slightly alkaline (pH ∼ 7.2–7.4), which is not conducive for nanomaterials that respond to acid but should destroy intracellular substances. Here, we proposed a new strategy for reconstructing the intracellular pH microenvironment to enhance photodynamic therapy. Nanomaterials (UCNP@ZIF + TPP + PA) were designed with an NaYF4:Yb:Tm (UCNP) inner core coated by a porous zeolitic imidazolate framework (ZIF-8) outside for photoacid (PA) and acid-responsive porphyrin (TPP) co-loading. Upon 980 nm laser irradiation, the emission light of UCNP activates PA for H+ release, which achieves reconstruction of the intracellular pH environment. In this new acid condition, TPP becomes protonated (TPP-H+), which reduces its aggregation by enhancing its water solubility, and in turn increases singlet oxygen (1O2) production for enhanced tumor killing. Both in vitro and in vivo experiments have proved that UCNP@ZIF + TPP + PA could reconstruct the intracellular pH environment and enhance therapeutic effect of photodynamic therapy (PDT). Reconstructing the intracellular pH by using light is of great significance for acid-responsive nanosystems to destroy intracellular substances and treat tumors. The results also signify the use of such acid-responsive materials for several other disease therapies.
中文翻译：
重建细胞内pH微环境以增强光动力疗法
酸性肿瘤微环境的特征是细胞外的弱酸性（pH约为6.5-7.0），已被证明是对特定酸敏感物质的潜在治疗靶标。但是，肿瘤细胞的细胞内pH仍为弱碱性（pH约为7.2-7.4），这不利于对酸有反应但会破坏细胞内物质的纳米材料。在这里，我们提出了一种重建细胞内pH微环境以增强光动力疗法的新策略。纳米材料（UCNP @ ZIF + TPP + PA）设计有NaYF 4：Yb：Tm（UCNP）内芯，外面包覆有多孔沸石咪唑酸酯骨架（ZIF-8），用于光酸（PA）和酸响应性卟啉（TPP） ）共同加载。在980 nm激光照射下，UCNP的发射光激活PA产生H +释放，实现细胞内pH环境的重建。在这种新的酸性条件下，TPP质子化（TPP-H +），通过增强其水溶性降低了其聚集，进而增加了单线态氧（1 O 2）的产生，从而增强了肿瘤的杀伤力。二者在体外和体内实验证明，UCNP @ ZIF + TPP + PA可以重构细胞内pH环境，增强光动力疗法（PDT）的治疗效果。通过光重建细胞内pH对于酸响应性纳米系统破坏细胞内物质和治疗肿瘤具有重要意义。该结果还表明将这种酸响应性材料用于其他几种疾病疗法。
更新日期：2020-01-13
中文翻译：
重建细胞内pH微环境以增强光动力疗法
酸性肿瘤微环境的特征是细胞外的弱酸性（pH约为6.5-7.0），已被证明是对特定酸敏感物质的潜在治疗靶标。但是，肿瘤细胞的细胞内pH仍为弱碱性（pH约为7.2-7.4），这不利于对酸有反应但会破坏细胞内物质的纳米材料。在这里，我们提出了一种重建细胞内pH微环境以增强光动力疗法的新策略。纳米材料（UCNP @ ZIF + TPP + PA）设计有NaYF 4：Yb：Tm（UCNP）内芯，外面包覆有多孔沸石咪唑酸酯骨架（ZIF-8），用于光酸（PA）和酸响应性卟啉（TPP） ）共同加载。在980 nm激光照射下，UCNP的发射光激活PA产生H +释放，实现细胞内pH环境的重建。在这种新的酸性条件下，TPP质子化（TPP-H +），通过增强其水溶性降低了其聚集，进而增加了单线态氧（1 O 2）的产生，从而增强了肿瘤的杀伤力。二者在体外和体内实验证明，UCNP @ ZIF + TPP + PA可以重构细胞内pH环境，增强光动力疗法（PDT）的治疗效果。通过光重建细胞内pH对于酸响应性纳米系统破坏细胞内物质和治疗肿瘤具有重要意义。该结果还表明将这种酸响应性材料用于其他几种疾病疗法。
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