2008 NSTI Nanotechnology Conference and Trade Show - Nanotech 2008 - 11th Annual

Partnering Events:

TechConnect Summit
Clean Technology 2008

Structural plasticity of transmembrane peptides allows generation of self-assembling uniform nanoparticles with innate biological activity

S.G. Tarasov, V. Gaponenko, O.M.Z. Howard, M. Dyba, S. Subramaniam, C.J. Michejda, N.I. Tarasova
National Cancer Institute at Frederick, US

self-assembly, drug delivery

Synthetic analogs of transmembrane domains of integral membrane proteins equipped with terminal negative charges were found to self-assemble into round nanoparticles in aqueous solutions. Particles can aggregate further forming strings and rings. Addition of PEG chains of defined length prevents superaggregation and leads to formation of stable and uniform particles with diameter around 12 nm. NMR studies of a derivative of the second transmembrane domain of CXCR4 have shown that peptide adopts a hairpin conformation with a small alpha-helix at the C-terminus. Upon fusion with cell membranes, peptide rearranges into alpha-helix and prevents correct assembly of the target protein. Association of hairpins into a nanoparticle appears to be mechanistically similar to formation of amyloid fibrils. Presence of an alpha-helix and negative charges is likely to force the curvature leading to round shapes rather than fibrils. Nanoparticular forms of transmembrane peptides are biologically active and inhibit the function of the corresponding membrane protein. Nanoparticular antagonist of CXCR4 inhibited growth of breast cancer cells in vitro and significantly prolonged life of mice in a mouse model of breast tumor dissipation. Nanoparticles formed by transmembrane peptides also efficiently encapsulated poorly soluble hydrophobic drugs, thus providing a unique delivery system with dual anti-tumor activity.

Nanotech 2008 Conference Program Abstract