bc9b00731_si_001.pdf (411.36 kB)
Versatile Reversible Cross-Linking Strategy to Stabilize CCMV Virus Like Particles for Efficient siRNA Delivery
journal contribution
posted on 2019-12-06, 14:45 authored by Chiara Pretto, Jan C. M. van HestVirus like particles obtained from the Cowpea Chlorotic
Mottle
Virus (CCMV) represent an innovative platform for drug delivery applications.
Their unique reversible self-assembly properties as well as their
suitability for both cargo loading and functionalization make them
a versatile scaffold for numerous purposes. One of the main drawbacks
of this platform is however its limited stability at physiological
conditions. Herein, we report the development of a general reversible
cross-linking strategy involving the homobifunctional cross-linker
DTSSP (3,3′-dithiobis (sulfosuccinimidylpropionate)) which
is suitable for particle stabilization. This methodology is adaptable
to different CCMV variants in the presence or absence of a stabilizing
cargo without varying neither particle shape nor size thus extending
the potential use of these protein cages in nanomedical applications.
Cross-linked particles are stable at neutral pH and 37 °C and
they are capable of protecting loaded cargo against enzymatic digestion.
Furthermore, the reversible nature of the cross-linking ensures particle
disassembly when they are taken up by cells. This was demonstrated
via the highly effective delivery of active siRNA into cells.
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particle shapeparticle stabilizationDTSSPCross-linked particlesplatformEfficient siRNA Delivery Virusprotein cagesStabilize CCMV Viruscross-linking strategyparticle disassemblydrug delivery applicationsnanomedical applicationsCCMV variantsVersatile Reversible Cross-Linking Strategyself-assembly propertiescargo loadingCowpea Chlorotic Mottle Virus
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