Smart temperature- and pH-responsive nanocarriers could be considered as potent vehicle in drug delivery systems. By this means, a thermo-responsive polymeric nanocarrier based on a random copolymer of poly(N-isopropylacrylamide-co-acrylamide) was prepared using controlled polymerization technique known as reversible addition fragmentation chain transfer (RAFT) polymerization. The presence of hydrophilic group in the chain, acrylamide, enhanced the lower critical solution temperature (LCST) to 37 °C in agreement with body normal temperature and made the structure suitable for drug delivery purposes. To reach this goal, the as-prepared structure was modified with hydrazine and then the anti-cancer drug, doxorubicin, was conjugated to hydrazine-modified chains through a Schiff-base linkage (acid-cleavable bond) to provide nanodrug carrier capable of responding to heat and pH. The product of each step was characterized with defined techniques. ¹HNMR spectroscopy provided data for molecular weight determination. The hydrodynamic size was figured out by dynamic light scattering to be less than 300 nm. A comprehensive study on the topology of nanodrug carrier was performed by scanning electron microscopy, and the structural changes below and above the LCST were followed by transmission electron microscopy and atomic force microscopy which showed coil-like composition to globule assembly at temperature above the LCST. Furthermore, the release pattern of nanodrug carrier was assessed in the simulated medium of healthy organs or cancer tissue with pH 7.4 and 5 (37 and 42 °C). Finally, the cytotoxicity assay was performed on breast cancer/MCF-7 cell line which showed high potential of nanodrug carrier as a highly intelligent anti-cancer agent.

中文翻译：

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基于聚（N-异丙基丙烯酰胺）的热敏纳米载体，可作为智能阿霉素递送系统

智能的对温度和pH敏感的纳米载体可被视为药物输送系统中的有效载体。通过这种方式，一个热响应高分子纳米载体基于聚的无规共聚物（Ñ -isopropylacrylamide-共-丙烯酰胺）是使用称为可逆加成断裂链转移（RAFT）聚合的受控聚合技术制备的。链中存在的亲水基团丙烯酰胺使临界溶液温度（LCST）降低至37°C，与人体正常温度一致，并使该结构适合药物递送目的。为了达到这个目标，先用肼修饰制备的结构，然后通过席夫碱键（酸可裂解键）将抗癌药阿霉素与肼修饰的链缀合，以提供能够响应的纳米药物载体加热和pH值。每个步骤的产物均采用定义的技术进行表征。^1个HNMR光谱提供了用于分子量测定的数据。通过动态光散射计算出流体动力学尺寸小于300nm。通过扫描电子显微镜对纳米药物载体的拓扑结构进行了全面的研究，然后在透射电子显微镜和原子力显微镜下观察了LCST上下的结构变化，结果表明在高于LCST的温度下，线圈状成分组装成球状。此外，在pH 7.4和5（37和42°C）的健康器官或癌组织的模拟培养基中评估了纳米药物载体的释放模式。最后，对乳腺癌/ MCF-7细胞系进行了细胞毒性测定，结果显示出纳米药物载体作为高度智能化的抗癌剂具有很高的潜力。