The development of elongated nanoparticles for drug delivery is of growing interest in recent years, due to longer blood circulation and improved efficacy compared to spherical counterparts. Squalenoyl-doxorubicin (SQ-Dox) conjugate was previously shown to form elongated nanoparticles with improved therapeutic efficacy and decreased toxicity compared to free doxorubicin. By using experimental and computational techniques, we demonstrate here that the specific physical properties of SQ-Dox, which include stacking and electrostatic interactions of doxorubicin as well as hydrophobic interactions of squalene, are involved in the formation of nanoassemblies with diverse elongated structures. We show that SQ-Dox bioconjugate concentration, ionic strength, and anion nature can be used to modulate the shape and stiffness of SQ-Dox nanoparticles. As those parameters are involved in nanoparticle behavior in biological media, these findings could bring interesting opportunities for drug delivery and serve as an example for the design of original nanodrugs with stacking properties tuned for particular clinical purposes.

Stacking as a key property for creating nanoparticles with tunable shape: The case of squalenoyl-doxorubicin

Dosio F.;Stella B.;
2019-01-01

Abstract

The development of elongated nanoparticles for drug delivery is of growing interest in recent years, due to longer blood circulation and improved efficacy compared to spherical counterparts. Squalenoyl-doxorubicin (SQ-Dox) conjugate was previously shown to form elongated nanoparticles with improved therapeutic efficacy and decreased toxicity compared to free doxorubicin. By using experimental and computational techniques, we demonstrate here that the specific physical properties of SQ-Dox, which include stacking and electrostatic interactions of doxorubicin as well as hydrophobic interactions of squalene, are involved in the formation of nanoassemblies with diverse elongated structures. We show that SQ-Dox bioconjugate concentration, ionic strength, and anion nature can be used to modulate the shape and stiffness of SQ-Dox nanoparticles. As those parameters are involved in nanoparticle behavior in biological media, these findings could bring interesting opportunities for drug delivery and serve as an example for the design of original nanodrugs with stacking properties tuned for particular clinical purposes.
2019
13
11
12870
12879
http://pubs.acs.org/journal/ancac3
bioconjugate; cylindrical nanoparticles; doxorubicin; elongated nanoparticles; nanomedicine; squalene; stacking
Mougin J.; Yesylevskyy S.O.; Bourgaux C.; Chapron D.; Michel J.-P.; Dosio F.; Stella B.; Ramseyer C.; Couvreur P.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1717700
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