2. Academic Validation
  3. Combined nanomedicines targeting colorectal cancer stem cells and cancer cells

Combined nanomedicines targeting colorectal cancer stem cells and cancer cells

  • J Control Release. 2020 Oct 10;326:387-395. doi: 10.1016/j.jconrel.2020.07.025.
Nikolaos Tsakiris 1,  Frédérique Fauvet 2,  Samia Ruby 2,  Alain Puisieux 2,  Adrien Paquot 3,  Giulio G Muccioli 3,  Arnaud M Vigneron 4,  Véronique Préat 5
Affiliations

Affiliations

  • 1 Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium.
  • 2 Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France; LabEx DEVweCAN, Université de Lyon, Lyon, France.
  • 3 Université Catholique de Louvain, Louvain Drug Research institute, Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Avenue Mounier 73,B1.72.01, 1200 Brussels, Belgium.
  • 4 Université de Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon, Equipe Labellisée Ligue contre le Cancer, Lyon, France; LabEx DEVweCAN, Université de Lyon, Lyon, France. Electronic address: [email protected].
  • 5 Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Avenue Mounier 73, B1.73.12, 1200 Brussels, Belgium. Electronic address: [email protected].
PMID: 32702392 DOI: 10.1016/j.jconrel.2020.07.025
Abstract

The study aims to combine the delivery of two Anticancer drugs to target both proliferating Cancer cells and dormant Cancer Stem Cells (CSCs) present in colorectal Cancer. Two drugs were selected and encapsulated in lipid nanocapsules: SN38, the active form of irinotecan, which is unstable in the plasma but active against replicating cells, and salinomycin, a highly toxic ionophore active against Cancer Stem Cells that is not suitable for clinical use. Using an engineered medium that enhanced the ratio of CSCs in HCT116 cell cultures, we demonstrated by clonogenicity tests and in sphere assays that Salinomycin acts mainly on CSCs, while SN38 acts mainly on proliferating Cancer cells. In a preclinical murine CRC model, encapsulation of both drugs in lipid nanocapsules reduced their toxicity, including hemolysis, and led to a higher survival than what was observed following treatment with single drugs or non-encapsulated drugs. Nanoparticles loaded with an Anticancer drug and salinomycin were effective against the therapy-resistant dormant CSCs and Cancer cells.

Keywords

Cancer stem cells; Colorectal cancer; Lipid nanocapsules; SN38; Salinomycin.

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