Design of new nano-tools to target mitochondria and study the metabolic plasticity of cancer cells
Résumé
Metabolic plasticity and mitochondrial function are crucial in tumorigenesis and cancer therapy response, making mitochondria a key target for novel treatments (1-2). Bioactive molecules, modulating mitochondrial activity, offer alternative therapies upon accumulation in mitochondria at effective doses (3). Theses molecules can be vectorized into mitochondria using nanovectors, improving their bioavaiability and reducing off-target effects (4). Our team has focused on the mitochondrial import marchinery, AIF/CHCHD4, essential for the control of mitochondria bioenergetics, cell survival & response to stress conditions (5). Our team has also identified a peptide that inhibits AIF/CHCHD4 interaction, representing a promising anticancer therapeutic potential (6). Due to the peptide's fragility, two nanovectorization approaches were developed to protect and deliver it to mitochondria: Liposomes & Fluorescent nano diamonds (Fig 1). Nanocarriers were characterized for the peotide encapsulation efficiency, size, stability & cellular uptake. Nano formulations were functionalized by specific mitochondria targeting moieties and are now under investigation for mitochondrial localization and cancer cell survival.
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