Second Generation Amphiphilic Poly-Lysine Dendrons Inhibit Glioblastoma Cell Proliferation without Toxicity for Neurons or Astrocytes.
Glioblastomas are the most common malignant primary brain tumours in adults and one of the most aggressive and difficult-to-treat cancers. No effective treatment exits actually for this tumour and new therapeutic approaches are needed for this disease. One possible innovative approach involves the nanoparticle-mediated specific delivery of drugs and/or genetic material to glioblastoma cells where they can provide therapeutic benefits. In the present work, we have synthesised and characterised several second generation amphiphilic polylysine dendrons to be used as siRNA carriers. We have found that, in addition to their siRNA binding properties, these new compounds inhibit the proliferation of two glioblastoma cell lines while being nontoxic for non-tumoural central nervous system cells like neurons and glia, cell types that share the anatomical space with glioblastoma cells during the course of the disease. The selective toxicity of these nanoparticles to glioblastoma cells, as compared to neurons and glial cells, involves mitochondrial depolarisation and reactive oxygen species production. This selective toxicity, together with the ability to complex and release siRNA, suggests that these new polylysine dendrons might offer a scaffold in the development of future nanoparticles designed to restrict the proliferation of glioblastoma cells.
Institute of Industrial Research, Warsaw, Poland.
Jolanta
J
Janiszewska
CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Asociada Neurodeath, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
Inmaculada
I
Posadas
CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Asociada Neurodeath, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
Pablo
P
Játiva
Institute of Organic Chemistry, PAS, Warsaw, Poland.
Marta
M
Bugaj-Zarebska
Institute of Organic Chemistry, PAS, Warsaw, Poland.
Zofia
Z
Urbanczyk-Lipkowska
CIBERNED, Instituto de Salud Carlos III, Madrid, Spain.|Unidad Asociada Neurodeath, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain.
Valentín
V
Ceña
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D011107:Polylysine