HER-2-mediated endocytosis of magnetic nanospheres and the implications in cell targeting and particle magnetization.
Polypyrrole-Fe3O4 nanospheres were synthesized via an emulsion polymerization method with hyaluronic acid as the surfactant. Hyaluronic acid offers the advantages of biocompatibility, cell adhesive property and the availability of functional groups for attachment of other molecules. The nanospheres were further functionalized with herceptin, and the efficacy of uptake of the functionalized nanospheres by human breast cancer cells was evaluated. It is envisioned that the combination of hyaluronic acid with its cell adhesive property and herceptin would result in high efficacy of internalization of the nanospheres by the cancer cells via a HER-2-mediated endocytosis. Our results showed that this is indeed the case and that the high concentration of herceptin-functionalized magnetic nanospheres in the cancer cells offers great potential in cancer cell targeting and treatment. In addition, the magnetic property of these nanospheres was also critically investigated and the magnetization was found to be affected by the particles' environment. The combination of these cell-targeting magnetic carriers with chemotherapeutic agents will be highly advantageous for the preferential killing of cancer cells in hyperthermia treatment.
Wuang
Shy Chyi
SC
Department of Chemical and Biomolecular Engineering, National University of Singapore, Kent Ridge, Singapore 119260.
Neoh
Koon Gee
KG
Kang
En-Tang
ET
Pack
Daniel W
DW
Leckband
Deborah E
DE
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology / Q000648:ultrastructure; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000502:physiology*; D005260:Female; D005562:Formazans / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D008027:Light; D008280:Magnetics; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012542:Scattering, Radiation; D013778:Tetrazolium Salts / Q000378:metabolism; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005562:Formazans; D018719:Erb-b2 Receptor Tyrosine Kinases; D013778:Tetrazolium Salts; D000068878:Trastuzumab; C079782:MTT formazan