California NanoSystems Institute , University of California, Los Angeles , Los Angeles , California 90095 , United States.
Department of Chemistry & Biochemistry , University of California, Los Angeles , Los Angeles , California 90095 , United States.
ACS Nano. 2018 May 22;12(5):4761-4774. doi: 10.1021/acsnano.8b01470. Epub 2018 Apr 30.
Serotonin-based nanoparticles represent a class of previously unexplored multifunctional nanoplatforms with potential biomedical applications. Serotonin, under basic conditions, self-assembles into monodisperse nanoparticles via autoxidation of serotonin monomers. To demonstrate potential applications of polyserotonin nanoparticles for cancer therapeutics, we show that these particles are biocompatible, exhibit photothermal effects when exposed to near-infrared radiation, and load the chemotherapeutic drug doxorubicin, releasing it contextually and responsively in specific microenvironments. Quantum mechanical and molecular dynamics simulations were performed to interrogate the interactions between surface-adsorbed drug molecules and polyserotonin nanoparticles. To investigate the potential of polyserotonin nanoparticles for in vivo targeting, we explored their nano-bio interfaces by conducting protein corona experiments. Polyserotonin nanoparticles had reduced surface-protein interactions under biological conditions compared to polydopamine nanoparticles, a similar polymer material widely investigated for related applications. These findings suggest that serotonin-based nanoparticles have advantages as drug-delivery platforms for synergistic chemo- and photothermal therapy associated with limited nonspecific interactions.
基于血清素的纳米粒子代表了一类以前未被探索的多功能纳米平台,具有潜在的生物医学应用。在碱性条件下,血清素单体通过自氧化自组装成单分散纳米粒子。为了展示多聚血清素纳米粒子在癌症治疗中的潜在应用,我们表明这些粒子是生物相容的,在近红外辐射下表现出光热效应,并负载化疗药物阿霉素,在特定的微环境中进行上下文相关和响应性的释放。进行了量子力学和分子动力学模拟,以探究表面吸附的药物分子与多聚血清素纳米粒子之间的相互作用。为了研究多聚血清素纳米粒子在体内靶向的潜力,我们通过进行蛋白质冠实验来探索它们的纳米-生物界面。与广泛研究用于相关应用的类似聚合物材料聚多巴胺纳米粒子相比,多聚血清素纳米粒子在生物条件下具有减少的表面蛋白相互作用。这些发现表明,基于血清素的纳米粒子作为协同化学-光热治疗的药物输送平台具有优势,与有限的非特异性相互作用有关。