Bioconjugate Chemistry p. 1098 - 1113 (2019)
Update date:2022-08-11
Topics:
Shchegravina, Ekaterina S.
Tretiakova, Daria S.
Alekseeva, Anna S.
Galimzyanov, Timur R.
Utkin, Yuri N.
Ermakov, Yuri A.
Svirshchevskaya, Elena V.
Negrebetsky, Vadim V.
Karpechenko, Natalia Yu.
Chernikov, Valery P.
Onishchenko, Natalia R.
Vodovozova, Elena L.
Fedorov, Alexey Yu.
Boldyrev, Ivan A.
Enzyme-responsive liposomes release their cargo in response to pathologically increased levels of enzymes at the target site. We report herein an assembly of phospholipase A2-responsive liposomes based on colchicinoid lipid prodrugs incorporated into lipid bilayer of the nanosized vesicles. The liposomes were constructed to addresses two important issues: (i) the lipid prodrugs were designed to fit the structure of the enzyme binding site; and (ii) the concept of lateral pressure profile was used to design lipid prodrugs that introduce almost no distortions into the lipid bilayer packing, thus ensuring that corresponding liposomes are stable. The colchicinoid agents exhibit antiproliferative activity in subnanomolar range of concentrations.
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