Design of Smart Nanogels that Respond to Physiologically Relevant pH Values and Temperatures
Design of Smart Nanogels that Respond to Physiologically Relevant pH Values and Temperatures
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响应生理相关 pH 值和温度的智能纳米凝胶的设计
DOI：
10.1166/jnn.2014.8551
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发表时间：
2014
影响因子：
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通讯作者：
and Patrick S. Stayton
中科院分区：
文献类型：
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作者：
Tomoyuki Omura;Mitsuhiro Ebara;James J. Lai;Xiangchun Yin;Allan S. Hoffman;and Patrick S. Stayton
在此，我们报告的单分散的“智能”纳米凝胶，表现出尖锐的体积相变在生理相关的温度和pH值的合成和表征。以N-异丙基丙烯酰胺（NIPAAm）和丙基丙烯酸（PAA）为单体，采用沉淀共聚法制备了纳米凝胶。简言之，在交联剂的存在下，在70 °C下使用0至10摩尔%的PAA进料进行反应。使用动态光散射（DLS）确定纳米凝胶颗粒的尺寸作为pH和温度的函数。在室温下，NIPAAm-PAA纳米凝胶是离散的球形结构，直径范围为200至250 nm。纳米凝胶的流体动力学直径减小至约100 nm。当溶液温度升高到37 °C时，100-150 nm。在37 °C下，当pKa低于NIPAAm-PAA的pKa时（约. 6.0）时，凝胶塌陷并聚集。然而，在37 °C和7.4的生理pH下，由于PAA的离子化羧基产生的电荷-电荷排斥，纳米凝胶没有完全塌陷。观察到类似的相变行为与相应的线性共聚物。因此，这种纳米凝胶颗粒可用于在局部酸中毒区域释放药物，包括感染部位、肿瘤、缺血和细胞内内体。
Herein, we report the synthesis and characterization of monodisperse ‘smart’ nanogels that exhibit a sharp volume phase transition at physiologically relevant temperatures and pH values. The nanogels were prepared by precipitation copolymerization of N-isopropylacrylamide (NIPAAm) and propylacrylic acid (PAA). Briefly, the reaction was performed using a PAA feed of between 0 and 10 mol% in the presence of a crosslinker at 70 °C. The size of the nanogel particles was determined as a function of pH and temperature using dynamic light scattering (DLS). At room temperature, the NIPAAm-PAA nanogels were discrete, spherical structures with diameters ranging from 200 to 250 nm. The hydrodynamic diameter of the nanogels decreased to ca. 100–150 nm when the solution temperature was increased to 37 °C. At 37 °C, when the pKa was below that of the NIPAAm-PAA (ca. 6.0), the gels collapsed and aggregated. However, at 37 °C and a physiological pH of 7.4, the nanogels did not fully collapse due to the charge–charge repulsion derived from the ionized carboxyl groups of the PAA. Similar phase transition behavior was observed with the corresponding linear copolymers. Thus, such nanogel particles could be useful for releasing drugs in regions of local acidosis, including sites of infection, tumors, ischemia, and intracellular endosomes.