Biotinylation of a MRI/Gd BNCT theranostic agent to access a novel tumour-targeted delivery system.
Alberto LanfrancoDiego AlbertiStefano ParisottoPolyssena RenziValentin LecomteSimonetta Geninatti CrichAnnamaria DeagostinoPublished in: Organic & biomolecular chemistry (2022)
A new biotin based BNCT (Boron Neutron Capture Therapy)-MRI theranostic is here reported (Gd-AL01) in order to exploit the high tumour specificity of biotin and the selectivity of BNCT in a synergistic manner. The key is the preparation of an intermediate where an o -carborane is linked to two amino groups orthogonally protected via the exploitation of two consecutive Mitsunobu reactions. The aim is its functionalisation in two different steps with biotin as the biological vector and Gd-DOTA as the MRI probe and GdNCT agent. Cell uptake was evaluated on HeLa tumour cells overexpressing biotin receptors. The internalised boron is proportional to the concentration of the theranostic agent incubated in the presence of cells. A maximum value of 77 ppm is reached and a well detectable signal intensity increase in the T 1 weighted image of HeLa cells was observed, differently from clinically used GdHPDO3A, where no contrast is detected. These excellent results indicate that Gd-AL01 can be applied as a theranostic probe in BNCT studies.
Keyphrases
- cell cycle arrest
- induced apoptosis
- contrast enhanced
- magnetic resonance imaging
- photodynamic therapy
- cell death
- magnetic resonance
- fluorescence imaging
- endoplasmic reticulum stress
- stem cells
- signaling pathway
- cancer therapy
- mass spectrometry
- oxidative stress
- quantum dots
- machine learning
- cell therapy
- bone marrow
- single cell
- cell proliferation
- high resolution
- fluorescent probe