Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
ACS Nano. 2011 Apr 26;5(4):2948-56. doi: 10.1021/nn103575a. Epub 2011 Mar 8.
Stimuli-responsive materials undergo structural changes in response to an external trigger (i.e., pH, heat, or light). This process has been previously used for a range of applications in biomedicine and microdevices and has recently gained considerable attention in controlled drug release. Here, we use a near-infrared (NIR) light responsive polymer-nanorod composite whose glass transition temperature (T(g)) is in the range of body temperature to control and enhance the release of a small-molecule drug (<800 Da). In addition to increased temperature and resulting changes in molecule diffusion, the photothermal effect (conversion of NIR light to heat) adjusts the composite above the T(g). Specifically, at normal body temperature (T < T(g)), the structure is glassy and release is limited, whereas when T > T(g), the polymer is rubbery and release is enhanced. We applied this heating system to trigger release of the chemotherapeutic drug doxorubicin from both polymer films and microspheres. Multiple cycles of NIR exposure were performed and demonstrated a triggered and stepwise release behavior. Lastly, we tested the microsphere system in vitro, reporting a ∼90% reduction in the activity of T6-17 cells when the release of doxorubicin was triggered from microspheres exposed to NIR light. This overall approach can be used with numerous polymer systems to modulate molecule release toward the development of unique and clinically applicable therapies.
刺激响应材料会对外界刺激（如 pH 值、温度或光）做出结构变化。这一过程已经在生物医学和微器件的一系列应用中得到了应用，并在最近的控制药物释放中引起了广泛关注。在这里，我们使用了一种近红外（NIR）光响应聚合物-纳米棒复合材料，其玻璃化转变温度（T(g)）在体温范围内，以控制和增强小分子药物（<800 Da）的释放。除了温度升高和由此导致的分子扩散变化外，光热效应（将 NIR 光转化为热）将复合材料的温度调整到 T(g)以上。具体来说，在正常体温（T < T(g)）下，结构呈玻璃态，释放受到限制，而当 T > T(g)时，聚合物呈橡胶态，释放得到增强。我们将这种加热系统应用于触发聚合物薄膜和微球中化疗药物阿霉素的释放。进行了多次 NIR 暴露循环实验，结果表明该系统具有触发和逐步释放的行为。最后，我们在体外测试了微球系统，当暴露于 NIR 光的微球触发阿霉素释放时，T6-17 细胞的活性降低了约 90%。这种整体方法可以与许多聚合物系统一起使用，以调节分子释放，从而开发独特且临床适用的治疗方法。
