白色的是可以分泌导致炎症物质的巨噬细胞，而纳米颗粒可以降解以后释放药物。（图片来源：Almutari Lab）
炎症是包括从感染到神经退行性疾病在内的很多人类疾病的特征。人体组织内的化学平衡被打破了，导致活性氧类（ROS，包括过氧化氢）积累起来，引起氧化应激和毒性反应。
尽管一些ROS对细胞信号转导和人体防御机制来说很重要，但是这些化学物质却会引发很多疾病，包括心血管疾病。同时它也是很多疾病的标志。非侵入性的方法如果可以检测重要而微量的过氧化氢和其他ROS的话，就能成为检测炎症的可行方法。这种方法同样可以把药物选择性地送至标靶。
加州大学圣地亚哥分校药学院纳米工程系的副教授Adah Almutairi博士和他的同事发明了首个可降解且对低浓度过氧化氢极其敏感的高聚物。即使在这样的低浓度下，过氧化氢仍然会影响生物功能。
向炎症部位靶向送药
他们的工作目前发表在《美国化学学会会刊》（Journal of the American Chemical Society）上。这些高聚物胶囊（或纳米颗粒）会被巨噬细胞和中性白细胞吸收，这两种免疫细胞会迅速赶到发炎部位，当它们随后开始产生过氧化氢的时候，纳米颗粒会被降解并释放其内容物。
“这是用生物相容的方法对氧化应激和炎症进行反应的第一个例子，”Almutairi说，“因为这胶囊被是可以被生物降解的，它们还能在遇到过氧化氢的时候释放携带的药物，所以可以成为疾病组织的靶向药物运输方法。”
Almutairi正在用动脉硬化作为模型检验这一方法。“心脏病学家长期以来一直需要一种非侵入的方法，在病人发病之前知道哪些人因动脉斑块破裂而导致的心脏病几率最大。”她说，“因为最危险的斑块都在发炎，所以我们的系统可以提供安全的方法检测并治疗这种疾病。”
Biocompatible Polymeric Nanoparticles Degrade and Release Cargo in Response to Biologically Relevant Levels of Hydrogen Peroxide
Caroline de Gracia Lux, Shivanjali Joshi-Barr, Trung Nguyen, Enas Mahmoud, Eric Schopf, Nadezda Fomina, Adah Almutairi.
Oxidative stress is caused predominantly by accumulation of hydrogen peroxide and distinguishes inflamed tissue from healthy tissue. Hydrogen peroxide could potentially be useful as a stimulus for targeted drug delivery to diseased tissue. However, current polymeric systems are not sensitive to biologically relevant concentrations of H2O2 (50–100 μM). Here we report a new biocompatible polymeric capsule capable of undergoing backbone degradation and thus release upon exposure to such concentrations of hydrogen peroxide. Two polymeric structures were developed differing with respect to the linkage between the boronic ester group and the polymeric backbone: either direct (1) or via an ether linkage (2). Both polymers are stable in aqueous solution at normal pH, and exposure to peroxide induces the removal of the boronic ester protecting groups at physiological pH and temperature, revealing phenols along the backbone, which undergo quinone methide rearrangement to lead to polymer degradation. Considerably faster backbone degradation was observed for polymer 2 over polymer 1 by NMR and GPC. Nanoparticles were formulated from these novel materials to analyze their oxidation triggered release properties. While nanoparticles formulated from polymer 1 only released 50% of the reporter dye after exposure to 1 mM H2O2 for 26 h, nanoparticles formulated from polymer 2 did so within 10 h and were able to release their cargo selectively in biologically relevant concentrations of H2O2. Nanoparticles formulated from polymer 2 showed a 2-fold enhancement of release upon incubation with activated neutrophils, while controls showed a nonspecific response to ROS producing cells. These polymers represent a novel, biologically relevant, and biocompatible approach to biodegradable H2O2-triggered release systems that can degrade into small molecules, release their cargo, and should be easily cleared by the body.
