Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-05-30

AUTHORS

Dunja Sobot, Simona Mura, Semen O Yesylevskyy, Laura Dalbin, Fanny Cayre, Guillaume Bort, Julie Mougin, Didier Desmaële, Sinda Lepetre-Mouelhi, Grégory Pieters, Bohdan Andreiuk, Andrey S Klymchenko, Jean-Louis Paul, Christophe Ramseyer, Patrick Couvreur

ABSTRACT

Once introduced in the organism, the interaction of nanoparticles with various biomolecules strongly impacts their fate. Here we show that nanoparticles made of the squalene derivative of gemcitabine (SQGem) interact with lipoproteins (LPs), indirectly enabling the targeting of cancer cells with high LP receptors expression. In vitro and in vivo experiments reveal preeminent affinity of the squalene-gemcitabine bioconjugates towards LP particles with the highest cholesterol content and in silico simulations further display their incorporation into the hydrophobic core of LPs. To the best of our knowledge, the use of squalene to induce drug insertion into LPs for indirect cancer cell targeting is a novel concept in drug delivery. Interestingly, not only SQGem but also other squalene derivatives interact similarly with lipoproteins while such interaction is not observed with liposomes. The conjugation to squalene represents a versatile platform that would enable efficient drug delivery by simply exploiting endogenous lipoproteins. More... »

PAGES

15678

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms15678

DOI

http://dx.doi.org/10.1038/ncomms15678

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1085710927

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28555624


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