SELF-ASSEMBLING DRUG-CONJUGATES FOR ANTI-CANCER TARGETING AND TREATMENT

Daniele Passarella

Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi 19, 20133 Milano, Italy

Abstract

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. In previous efforts we used squalene tail as a self-assembling inducer [1] 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 conjugates and fluorescein-squalene conjugates [3].

In order to address the highly demanding issue of resistance [4] we studied the formation of cyclopamine-paclitaxel containing nanoparticles, and we characterized their internalization by confocal microscopy and super-resolution [5]. Our efforts are actually focused on: a) new combination of drugs to overcome drug resistance, b) new self-assembling inducers [6], c) new hetero-nanoparticles and d) new drug-conjugates deriving by modification of bioactive natural products.

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. Chem Plus Chem 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. Chem Plus Chem 2015, 9, 1380.
[6] G. Fumagalli, D. Passarella et al. Org. Biomol. Chem., 2017, 15, 1106.