IBMM, Univ. Montpellier, CNRS, ENSCM; Avenue Charles Flahault, CEDEX 05, 34093 Montpellier, France.
ICGM, Univ Montpellier-CNRS-ENSCM, 34090 Montpellier, France.
ACS Appl Mater Interfaces. 2021 Jun 30;13(25):29325-29339. doi: 10.1021/acsami.1c05848. Epub 2021 Jun 17.
We report periodic mesoporous ionosilica nanoparticles (PMINPs) as versatile nano-objects for imaging, photodynamic therapy (PDT), and efficient adsorption and delivery of small interfering RNA (siRNA) into breast cancer cells. In order to endow these nanoparticles with PDT and siRNA photochemical internalization (PCI) properties, a porphyrin derivative was integrated into the ionosilica framework. For this purpose, we synthesized PMINPs hydrolysis-cocondensation procedures from oligosilylated ammonium and porphyrin precursors. The formation of these nano-objects was proved by transmission electron microscopy. The formed nanoparticles were then thoroughly characterized solid-state NMR, nitrogen sorption, dynamic light scattering, and UV-vis and fluorescence spectroscopies. Our results indicate the formation of highly porous nanorods with a length of 108 ± 9 nm and a width of 54 ± 4 nm. A significant PDT effect of type I mechanism (95 ± 2.8% of cell death) was observed upon green light irradiation in nanoparticle-treated breast cancer cells, while the blue light irradiation caused a significant phototoxic effect in non-treated cells. Furthermore, PMINPs formed stable complexes with siRNA (up to 24 h), which were efficiently internalized into the cells after 4 h of incubation mostly with the energy-dependent endocytosis process. The PCI effect was obvious with green light irradiation and successfully led to 83 ± 1.1% silencing of the luciferase gene in luciferase-expressing breast cancer cells, while no gene silencing effect was observed with blue light irradiation. The present work highlights the high potential of porphyrin-doped PMINPs as multifunctional nanocarriers for nucleic acids, such as siRNA, with a triple ability to perform imaging, PDT, and PCI.
我们报道了周期性介孔离子硅纳米颗粒（PMINPs）作为多功能纳米客体，用于乳腺癌细胞的成像、光动力疗法（PDT）以及小干扰 RNA（siRNA）的高效吸附和递释。为了赋予这些纳米颗粒 PDT 和 siRNA 光化学内化（PCI）的特性，我们将卟啉衍生物整合到离子硅骨架中。为此，我们通过硅烷化铵和卟啉前体的水解共缩合程序合成了 PMINPs。通过透射电子显微镜证明了这些纳米客体的形成。然后通过固态 NMR、氮气吸附、动态光散射以及紫外可见和荧光光谱对形成的纳米颗粒进行了全面的表征。我们的结果表明形成了具有 108±9nm 长度和 54±4nm 宽度的高度多孔纳米棒。在纳米颗粒处理的乳腺癌细胞中，用绿光照射时观察到显著的 I 型机制 PDT 效应（95±2.8%的细胞死亡），而蓝光照射在未经处理的细胞中会产生显著的光毒性效应。此外，PMINPs 与 siRNA 形成稳定的复合物（长达 24 小时），在孵育 4 小时后，主要通过能量依赖性内吞作用有效地将其内化到细胞中。用绿光照射时，PCI 效应明显，并成功地导致在表达荧光素酶的乳腺癌细胞中使荧光素酶基因沉默 83±1.1%，而蓝光照射时则没有基因沉默效应。本工作突出了卟啉掺杂的 PMINPs 作为多功能核酸纳米载体的高潜力，例如 siRNA，具有成像、PDT 和 PCI 的三重能力。
