Our continuous interest in the field of chemical approaches to target cancer cells moved us to study the preparation of a novel classes of conjugate compounds using anticancer drugs as building blocks. We used squalene tail as self-assembling inducer1 and a disulphide containing linker to secure the release of the drugs after cell internalization.2 Subsequently we demonstrated the possibility to generate hetero and fluorescent nanoparticles by mixing a paclitaxel-squalene conjugate and fluorescein-squalene conjugate.3 In the light of facing the high demanding issue of resistance4 we studied the formation of cyclopamine-paclitaxel containing nanoparticles and we detected the cell internalization by confocal microscopy and super-resolution.5 More recently we reported doxorubicin-cyclopamine hetero-nanoparticles that are able to reduce tumour growth and to decrease the toxicity of chemotherapy in mice.6 We also applied the same approach to obtain trehalose conjugates and nano-assemblies to face neurodegeneration.7
Our efforts are actually focused on: a) new combination of drugs to overcome drug resistance,8 b) new drug-conjugates deriving by modification of active natural products,9and c) new self-assembling inducers.10,11,12
References
[1] G. Fumagalli,D. Passarella et al. Drug Discovery Today 2016, 21, 1321
[2] S. Borrelli, A. D. Passarella et al. Eur.J.Med.Chem 2014, 85, 179
[3] G. Fumagalli, D. Passarella et al. ChemPlusChem 2015, 80, 47
[4] P.A. Sotiropoulou, C. Herold-Mende, D. Passarella et al. Drug Discovery Today 2014, 19, 1547
[5] G. Fumagalli, D. Passarella et al. ChemPlusChem 2015, 9, 1380
[6] G. Fumagalli, D. Passarella et al. ACS Med.Chem.Lett. 2017, 8, 953
[7] E. Colombo, P. Seneci, D. Passarella Pharmaceutics 2019, 11, 422
[8] G. Fumagalli, D. Passarella et al. ACS Med.Chem.Lett. 2018, 9, 468
[9] G. Fumagalli, E. Colombo, F. Foschi, D. Passarella et al. ACS Med.Chem.Lett., 2019, 10, 611
[10] G. Fumagalli, D. Passarella et al. Org. Biomol. Chem., 2017, 15, 1106
[11] E. Colombo, D. Passarella et al. ACS Med. Chem.Lett 2020, 11, 895
[12] A. I. Antoniou, D. Passarella et al. Pharmaceuticals 2023, 16 (5), 722