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ONCOLOGY NANOMEDICINE: Study of Interactions Between Nanoparticles Activated by External Electromagnetic Energy Sources and Cancer Cells for Enhancement of the Therapeutic Window

Type
Thesis
Keywords
  • Nanomedicine
  • Cancer
  • Nanoparticles
  • Radiotherapy
  • Residence
  • Electromagnetic Energy Sources
  • Tumour Cells
  • Nanoparticles Interaction
  • Cell Trafficking
  • Endosome Residence
  • Therapeutic Window
  • Pharmacokinetic
  • Biodistribution

Abstract

The understanding of interactions between nanomaterials and biological entities is fundamental to develop nanoproducts in oncology. NBTXR3 (hafnium oxide inert nanoparticle) and protoporphyrin IX (Pp IX) nanocarrier (silica nanoparticle encapsulating PpIX, the monomer of Photofrin®) are nanoproducts, issued from Nanobiotix platforms, aim to enlarge the therapeutic window of oncology treatment, using external energy sources to carry out “on” / “off” activation. In the first part of this work, we have studied interaction between NBTXR3 and human colon cancer cells. NBTXR3 penetrates by endocytosis and presents long residence within endo-lysosomal compartment. Significantly enhance of tumour cell radiation response is demonstrated after NBTXR3 activation with ionizing radiation. Compared to controls, irradiated cells having internalized NBTXR3, offer a particular morphology which is described. In the second part, we present the synthesis of a new hybrid nanoproduct for photodynamic therapy (PDT), the Pp IX nanocarrier, and the study of its interaction in vitro on six human cancer cell lines and in vivo on nude mice model xenografted with three different cancer types. In vitro, Pp IX nanocarrier activated at 630 nm is more efficient than free Pp IX. Further, this new hybrid nanoproduct enhances biodistribution of Pp IX, with different kinetic of tumour accumulation between models. Ultimately, based on these new understanding of interactions between nanoparticles and cancer cells, both NBTXR3 nanoparticle and Pp IX nanocarrier, offer a breakthrough approach to create efficient pathways to cancer therapy.

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