Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), UMR-7504, CNRS-Université de Strasbourg, 23 rue du Loess, BP 34 67034, Strasbourg Cedex 2, France.
INSERM UMR_S1109, Tumor Biomechanics, Strasbourg, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
J Colloid Interface Sci. 2019 Apr 15;542:469-482. doi: 10.1016/j.jcis.2019.01.098. Epub 2019 Jan 23.
The engineering of luminescent nanoplatforms for biomedical applications displaying ability for scaling-up, good colloidal stability in aqueous solutions, biocompatibility, and providing an easy detection in vivo by fluorescence methods while offering high potential of functionalities, is currently a challenge. The original strategy proposed here involves the use of large pore (ca. 15 nm) mesoporous silica (MS) nanoparticles (NPs) having a stellate morphology (denoted STMS) on which fluorescent InP/ZnS quantum dots (QDs) are covalently grafted with a high yield (≥90%). These nanoplatforms are after that further coated to avoid a potential QDs release. To protect the QDs from potential release or dissolution, two wrapping methods are developed: (i) a further coating with a silica shell having small pores (≤2 nm) or (ii) a tight polysaccharide shell deposited on the surface of these STMS@QDs particles via an original isobutyramide (IBAM)-mediated method. Both wrapping approaches yield to novel luminescent nanoplatforms displaying a highly controlled structure, a high size monodispersity (ca. 200 and 100 nm respectively) and colloidal stability in aqueous solutions. Among both methods, the IBAM-polysaccharide coating approach is shown the most suitable to ensure QDs protection and to avoid metal cation release over three months. Furthermore, these original STMS@QDs@polysaccharide luminescent nanoplatforms are shown biocompatible in vitro with murine cancer cells and in vivo after injections within zebrafish (ZF) translucent embryos where no sign of toxicity is observed during their development over several days. As assessed by in vivo confocal microscopy imaging, these nanoplatforms are shown to rapidly extravasate from blood circulation to settle in neighboring tissues, ensuring a remanent fluorescent labelling of ZF tissues in vivo. Such fluorescent and hybrid STMS composites are envisioned as novel luminescent nanoplatforms for in vivo fluorescence tracking applications and offer a versatile degree of additional functionalities (drug delivery, incorporation of magnetic/plasmonic core).
用于生物医学应用的发光纳米平台的工程设计,要求其具有扩大规模的能力、在水溶液中具有良好的胶体稳定性、生物相容性,并能够通过荧光方法进行体内简便检测,同时提供高功能潜力,这是当前的一个挑战。这里提出的原始策略涉及使用具有星型形态的大孔(约 15nm)介孔硅纳米颗粒(MS NPs)(表示为 STMS),其上通过高收率(≥90%)共价接枝荧光 InP/ZnS 量子点(QDs)。这些纳米平台随后进一步进行包覆以避免 QDs 的潜在释放。为了防止 QDs 潜在的释放或溶解,开发了两种包覆方法:(i)进一步包覆具有小孔(≤2nm)的二氧化硅壳,或(ii)通过原始异丁酰胺(IBAM)介导的方法在这些 STMS@QDs 颗粒表面沉积紧密的多糖壳。这两种包覆方法都得到了具有高度可控结构、高单分散性(分别约为 200nm 和 100nm)和在水溶液中胶体稳定性的新型发光纳米平台。在这两种方法中,IBAM-多糖包覆方法被证明最适合确保 QDs 的保护并避免在三个月内释放金属阳离子。此外,这些原始的 STMS@QDs@polysaccharide 发光纳米平台在体外与鼠癌细胞和斑马鱼(ZF)透明胚胎体内表现出生物相容性,在数天的发育过程中未观察到毒性迹象。通过体内共聚焦显微镜成像评估,这些纳米平台被证明能够迅速从血液循环中外渗到邻近组织中,确保在体内对 ZF 组织进行残留荧光标记。这种荧光和杂化 STMS 复合材料有望成为用于体内荧光跟踪应用的新型发光纳米平台,并提供多功能程度的额外功能(药物输送、掺入磁性/等离子体核)。