Verteporfin-loaded mesoporous silica nanoparticles inhibit mouse melanoma proliferation in vitro and in vivo

J Photochem Photobiol B. 2019 Aug:197:111533. doi: 10.1016/j.jphotobiol.2019.111533. Epub 2019 Jun 13.

Abstract

Melanoma is one of the most lethal tumors among the skin cancers, arising from complex genetic mutations in melanocyte. Melanoma microenvironment is very heterogeneous, showing complex vascular networks and immunogenicity, as well as induced acquired resistance to treatments by upregulation of multidrug resistance (MDR) mechanisms. Different studies have showed that Photodynamic Therapy (PDT) could be considered a new potential approach for melanoma treatment. PDT combines a light with a specific wavelength and a photosensitizer: when these two elements interact reactive oxygen species (ROS) are generated leading to tumor cell destruction. In this study verteporfin (Ver), a second-generation photosensitizer, has been conjugated with mesoporous silica nanoparticles (MSNs): the resulting Ver-MSNs are an efficient nanoplatforms used to enhance cargo capacity and cellular uptake. Our in vitro and in vivo studies investigated whether Ver-MSNs were able to reduce or inhibit melanoma growth. In vitro experiments performed using B16F10 mouse melanoma cells showed that Ver-MSNs stimulated by red light (693 nm) significantly decreased in vitro cells proliferation in a range of concentration between 0.1 μg/ml to 10 μg/ml. When Ver-MSNs (5 μg/ml in glycerol) were topically administrated to melanoma tumor mass developed in mice and stimulated by red light for four times in 16 days, they were able to reduce the tumor mass of 50.2 ± 6,6% compared to the untreated (only glycerol) mice. In the light of this information, PDT performed using Ver-MSNs could be considered a new promising and potential approach to treat melanoma.

Keywords: B16F10 cells; Melanoma; Mesoporous silica nanoparticles; Photodynamic therapy; ROS; Verteporfin.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Carriers / chemistry
  • Female
  • Light
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Metal Nanoparticles / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Photochemotherapy
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / therapeutic use
  • Porosity
  • Reactive Oxygen Species / metabolism
  • Silicon Dioxide / chemistry*
  • Verteporfin / chemistry*
  • Verteporfin / therapeutic use

Substances

  • Drug Carriers
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • Verteporfin
  • Silicon Dioxide