Selective and active targeting of neuropeptide Y receptors in experimental oncology: use of gold nanocages conjugated to short peptides
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Data di Pubblicazione:
2015
Citazione:
Selective and active targeting of neuropeptide Y receptors in experimental oncology: use of gold nanocages conjugated to short peptides / C. Macchi, M. Ruscica, S. Avvakumova, E. Galbiati, S. Romeo, D. Prosperi, P. Magni. ((Intervento presentato al convegno SIPMeT tenutosi a Alba nel 2015.
Abstract:
Background. Neuroendocrine molecules, such as neuropeptide Y (NPY), play a significant role in the development of human cancers, such as breast (BrCa) and prostate (PCa) carcinomas. Interaction between NPY and its Y receptors (Y-Rs) influences cancer progression leading to tumour growth modulation. Y1-R controls cell proliferation, whereas Y2-R promotes angiogenesis. Moreover, a switch from Y2-R expression in normal breast to a Y1-expression in BrCa has been reported. Thus, the development of molecular tools to specifically target Y-Rs are promising for novel diagnostic and therapeutic approaches. Among them, gold nanoparticles are very useful for selective cancer cell targeting due to their low toxicity and simple functionalization with peptides and antibodies leading to high binding affinity and multivalent avidity. Gold nanocages (AuNCs) characterized by hollow interiors, ultrathin and porous walls are of interest due to their strong and highly wavelength-tunable optical absorption in the near-infrared optical window.
Aim. We used AuNCs as a carrier for selective targeting of Y1- and Y2-R in a well-characterized cancer model expressing Y-Rs, the PC-3 human androgen-independent PCa cells. To this purpose, AuNCs have been functionalized with short peptide sequences recognising Y1- and Y2-R.
Results. Au-peptide NCs ability to target Y1- and Y2-R in PC-3 cells was evaluated by confocal microscopy. After 15 min of incubation, only Au-peptide NCs were detected at the cellular membrane. One to 3-h incubation resulted in Au-peptide NCs translocation into the cells. Annexin V and MTT assays did not show any cytotoxic effect driven by Au-peptide NCs.
PC-3 cells treatment with Au-peptide NCs, AuNCs or peptides resulted in a differential pattern of activation of ERK1/2 phosphorylation (Western Blot analysis).
Conclusions. These information will help us to establish whether the presence of AuNCs can positively or negatively affect peptide actions on cancer cell response.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
C. Macchi, M. Ruscica, S. Avvakumova, E. Galbiati, S. Romeo, D. Prosperi, P. Magni
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