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Silver Nanoparticles Covered with pH-Sensitive Camptothecin-Loaded Polymer Prodrugs: Switchable Fluorescence “Off” or “On” and Drug Delivery Dynamics in Living Cells
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-11-09 00:00:00 , DOI: 10.1021/acsami.7b14070 Liang Qiu 1, 2 , Jia-Wei Li 2 , Chun-Yan Hong 2 , Cai-Yuan Pan 2
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-11-09 00:00:00 , DOI: 10.1021/acsami.7b14070 Liang Qiu 1, 2 , Jia-Wei Li 2 , Chun-Yan Hong 2 , Cai-Yuan Pan 2
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A unique drug delivery system, in which silver nanoparticles (AgNPs) are covered with camptothecin (CPT)-based polymer prodrug, has been developed, and the polymer prodrug, in which the CPT is linked to the polymer side chains via an acid-labile β-thiopropionate bond, is prepared by RAFT polymerization. For poly(2-(2-hydroxyethoxy)ethyl methacrylate-co-methacryloyloxy-3-thiahexanoyl-camptothecin)@AgNPs [P(HEO2MA-co-MACPT)@AgNPs], the polymer thickness on the AgNP surface is around 5.9 nm (TGA method). In vitro tests in buffer solutions at pH = 7.4 reveal that fluorescence of the CPT in the hybrid nanoparticles is quenched due to the nanoparticle surface energy transfer (NSET) effect, but under acidic conditions, the CPT fluorescence is gradually recovered with gradual release of the CPT molecules from the hybrid nanoparticles through cleavage of the acid-labile bond. The NSET “on” and “off” is induced by the CPT–AgNP distance change. This unique property makes it possible to track the CPT delivery and release process from the hybrid nanoparticles in the living cells in a real-time manner. The internalization and intracellular releasing tests of the hybrid nanoparticles in the HeLa cells demonstrate that the lysosome containing the hybrid nanoparticles displays CPT blue fluorescence due to release of the CPT under acidic conditions, and the drug-releasing kinetics shows fluorescence increase of the released CPT with incubation time. The cytotoxicity of hybrid nanoparticles is dependent on activity of the acid-labile bond. Therefore, this is a potential efficient drug delivery system in cancer therapy and a useful approach to study the mechanism of release process in the cells.
中文翻译：
pH敏感的喜树碱载聚合物前药覆盖的银纳米颗粒：“关”或“开”的可切换荧光以及活细胞中的药物传递动力学
已经开发了一种独特的药物递送系统，其中银纳米颗粒（AgNP）被喜树碱（CPT）基聚合物前药覆盖，并且该聚合物前药中CPT通过对酸不稳定的方式连接至聚合物侧链β-硫代丙酸酯键是通过RAFT聚合制备的。对于聚（2-（2-羟基乙氧基）乙基甲基丙烯酸酯共甲基丙烯酰氧基-3- thiahexanoyl -喜树碱）@AgNPs [P（HEO 2 MA-共-MACPT）@AgNPs]时，AgNP表面上的聚合物厚度约为5.9 nm（TGA方法）。体外在pH = 7.4的缓冲溶液中进行的测试表明，由于纳米颗粒表面能转移（NSET）的作用，杂化纳米颗粒中CPT的荧光被淬灭，但是在酸性条件下，随着CPT分子的逐渐释放，CPT荧光逐渐被恢复通过裂解酸不稳定键从杂化纳米颗粒中分离出来。NSET“开”和“关”是由CPT-AgNP距离变化引起的。这种独特的特性使得可以实时跟踪活细胞中杂化纳米粒子的CPT传递和释放过程。HeLa细胞中杂交纳米颗粒的内在化和细胞内释放测试表明，由于在酸性条件下CPT的释放，含有杂交纳米颗粒的溶酶体显示出CPT蓝色荧光，药物释放动力学表明，随着培养时间的延长，释放的CPT的荧光增强。杂化纳米颗粒的细胞毒性取决于酸不稳定键的活性。因此，这是在癌症治疗中潜在的有效药物递送系统，并且是研究细胞中释放过程机制的有用方法。
更新日期：2017-11-09
中文翻译：
pH敏感的喜树碱载聚合物前药覆盖的银纳米颗粒：“关”或“开”的可切换荧光以及活细胞中的药物传递动力学
已经开发了一种独特的药物递送系统，其中银纳米颗粒（AgNP）被喜树碱（CPT）基聚合物前药覆盖，并且该聚合物前药中CPT通过对酸不稳定的方式连接至聚合物侧链β-硫代丙酸酯键是通过RAFT聚合制备的。对于聚（2-（2-羟基乙氧基）乙基甲基丙烯酸酯共甲基丙烯酰氧基-3- thiahexanoyl -喜树碱）@AgNPs [P（HEO 2 MA-共-MACPT）@AgNPs]时，AgNP表面上的聚合物厚度约为5.9 nm（TGA方法）。体外在pH = 7.4的缓冲溶液中进行的测试表明，由于纳米颗粒表面能转移（NSET）的作用，杂化纳米颗粒中CPT的荧光被淬灭，但是在酸性条件下，随着CPT分子的逐渐释放，CPT荧光逐渐被恢复通过裂解酸不稳定键从杂化纳米颗粒中分离出来。NSET“开”和“关”是由CPT-AgNP距离变化引起的。这种独特的特性使得可以实时跟踪活细胞中杂化纳米粒子的CPT传递和释放过程。HeLa细胞中杂交纳米颗粒的内在化和细胞内释放测试表明，由于在酸性条件下CPT的释放，含有杂交纳米颗粒的溶酶体显示出CPT蓝色荧光，药物释放动力学表明，随着培养时间的延长，释放的CPT的荧光增强。杂化纳米颗粒的细胞毒性取决于酸不稳定键的活性。因此，这是在癌症治疗中潜在的有效药物递送系统，并且是研究细胞中释放过程机制的有用方法。
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