Synthetic polymer hydrogel nanoparticles (NPs) capable of capturing and/or releasing target biomacromolecules are of interest as alternative bioaffinity ligands. Recently, poly-N-isopropylacrylamide (pNIPAm) based NPs have been prepared with the capacity to bind and neutralize the hemolytic toxin melittin. These NPs were found to neutralize the toxicity of melittin in vivo. In the present study, we focused on developing a synthetic NP for anticancer therapy by capturing and inhibiting the vascular endothelial growth factor (VEGF). Cancer cells secrete a number of growth factors to create new blood vessels in a process known as �angiogenesis�. VEGF165 is the most important angiogenesis growth factor. Polymer NPs were prepared by precipitation polymerization from solutions of monomers containing complementary functional groups that included sulfated N-acetylglucosamine monomers in addition to NIPAm, N-tert-butylacrylamide (TBAm, a hydrophobic monomer), and N,N'methylenebisacrylamide (Bis, a crosslnker)(Fig. 1a). A quartz crystal microbalance (QCM) sensor functionalized with VEGF165 was used to screen the NP library for protein binding (Fig. 1b). Interestingly, the NP affinity for VEGF165 was found to be very sensitive to the relative amounts of functional monomers (Fig. 1c). An optimized NP containing sulfated N-acetylglucosamine monomers strongly inhibited the phosphorylation (Tyr951) of VEGF receptor in vitro. This biologically inspired nanoparticle may very well point the way to a novel and cost effective cancer therapeutic agent.

Synthetic polymer nanoparticle with engineered affinity for a vascular endothelial growth factor (VEGF)

248th National Meeting (2014)

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