Self-assembly of prodrugs formed by cell-penetrating peptide and ferrocifen for lung cancer treatment

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TitreSelf-assembly of prodrugs formed by cell-penetrating peptide and ferrocifen for lung cancer treatment
Type de publicationCommunication
TypeCommunication sans actes dans un congrès
Date du colloque26-29/09/2018
Titre du colloqueImaging and therapeutic targeting in cancerology: New advances and trends in preclinical and clinical studies
AuteurGuyon, Léna , Lepeltier, Elise , Jaouen, Gérard
2, 3
, Pigeon, Pascal
2, 3
, Perino, Didier , Passirani-Malleret, Catherine
VilleLe Bono
Résumé en anglais

Considering that lung carcinoma is the major cause of cancer-related death worldwide, the main objective is to find new treatments through a nebulization therapy. In this project, a new class of molecules developed by the start-up called Feroscan has been studied: ferrocifens. They have powerful in vitro anticancer properties but are highly insoluble in water, requiring a formulation stage before being in vivo administered [1]. The objective of this project is to combine three strategies to vectorize ferrocifens: a combination of cell-penetrating peptides (CPP), prodrug and self-assembly. The coupling of a hydrophilic CPP (Argn, n=6-9) with a hydrophobic drug should facilitate the release mainly in the targeted cancer cells [2].

Concretely, CPP were prepared by solid-phase peptide synthesis using a standard 9-fluorenylmethoxycarbonyl (Fmoc) chemistry and a ferrocifen containing a carboxylic function (p54) was linked to the N-terminal extremity of the peptide. After the cleavage, Argn-ferrocifen conjugates were purified by preparative reverse-phase high-performance chromatography and nanoassemblies were formulated by a solvent displacement technique using a microfluidic device. A comparison of their biological activities was performed in vitro on human lung cancer cells (A549 cell line).

Argn-p54 were synthesized with a yield between 30 % and 70 % and a purity of 90 %. Subsequently, nanoassemblies were obtained with an apparent diameter of 150 nm, a polydispersity index of 0.15 and a drug loading of 30 %. Preliminary in vitro studies showed that Arg7-p54 is more active than the other conjugates. The complete characterization of nanoassemblies formed, via the determination of the supramolecular organization, will be investigated by cryo-TEM analysis and synchrotron radiation small-angle X-ray scattering.


[1] G. Jaouen, A. Vessieres and S. Top. Royal Society of chemistry, 2015, 8802-88017.

[2] F. Wang, Y. Wang, X. Zhang, W. Zhang, S. Guo, F. Jin. Journal of Controled Release, 2014, 126–136.

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