Periodic Mesoporous Ionosilica Nanoparticles for Green Light Photodynamic Therapy and Photochemical Internalization of siRNA

ACS Appl Mater Interfaces. 2021 Jun 30;13(25):29325-29339. doi: 10.1021/acsami.1c05848. Epub 2021 Jun 17.

Abstract

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 via 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 via 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.

Keywords: gene silencing; periodic mesoporous ionosilica nanoparticles; photochemical internalization; photodynamic therapy; siRNA.

MeSH terms

  • Cells, Cultured
  • Gene Silencing
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Nanoparticles / chemistry*
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry*
  • RNA, Small Interfering / chemistry*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Silicon Dioxide / chemistry*

Substances

  • Photosensitizing Agents
  • RNA, Small Interfering
  • Silicon Dioxide