Multifunctional Polymeric Nanoparticles from Diverse Bioactive Agents
Bertin, P.A., Gibbs, J.M., Shen, C.K.F., Thaxton, C.S., Russin, W.A., Mirkin, C.A., Nguyen, S.T. J. Amer. Chem. Soc.,128, 4168-4169 (April 5, 2006).
Scientists at Northwestern University have used a ring-opening metathesis polymerization method to create nanoparticles with a core, which may be used to carry drugs, and a shell surface that permits attachment of single-stranded DNA or tumor-targeting antibodies. The spherical structures were confirmed with transmission electron microscopy as having diameters less than 200 nm. Tosyl groups on the shell surface were used to attach single-stranded oligonucleotides via 5’-terminal amines and antibodies via amines on such amino acids as lysine. Transmission electron microscopy confirmed the attachment of the biologically active moieties. Moreover, when the nanoparticles were conjugated with both anti-HER-2 IgY and Bcl-2 antisense oligodeoxynucleotides, human breast carcinoma cells that overexpress the HER-2 protein internalized the nanoparticles. Exposure of the cells to Bcl-2 alone or to nanoparticles lacking the HER-2 antibodies showed no uptake. Hence, the HER-2 antibodies facilitate the entry of the nanoparticles into the cell.
The authors previously have shown that chemotherapeutic agents can be sequestered in their nanoparticles’ cores. Merging that approach with the one used in the present study should yield a wide range of anticancer therapies, delivered with specificity and with the potential for obtaining synergistic effects of different drug combinations.
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