Lipid-encapsulation of surface enhanced Raman scattering (SERS) nanoparticles and targeting to chronic lymphocytic leukemia (CLL) cells

60 nm diameter gold nanoparticles (AuNP) were coated with a ternary mixture of lipids and targeted to human lymphocytes. Previously, the versatility, stability and ease of application of the lipid coating was demonstrated by the incorporation of three classes of Raman-active species. In the present study, lipid encapsulated AuNPs were conjugated to two targeting species, namely whole antibodies and antibody fragments (Fab), by two methods. Furthermore, in vitro targeting of lipid-encapsulated Au nanoparticles to patient-derived chronic lymphocytic leukemia (CLL) cells was demonstrated by Raman spectroscopy, Raman mapping, and darkfield microscopy. These results further demonstrate the versatility of the lipid layer for imparting stability, SERS activity, and targeting capability, which make these particles promising candidates for biodiagnostics.

[1]  E Gratton,et al.  Lipid rafts reconstituted in model membranes. , 2001, Biophysical journal.

[2]  George C. Schatz,et al.  The Optical Properties of Metal Nanoparticles: The Influence of Size, Shape, and Dielectric Environment , 2003 .

[3]  Ting Li,et al.  Comparative toxicity study of Ag, Au, and Ag–Au bimetallic nanoparticles on Daphnia magna , 2010, Analytical and bioanalytical chemistry.

[4]  John Paul Pezacki,et al.  Development of nanoparticle probes for multiplex SERS imaging of cell surface proteins. , 2010, Nanoscale.

[5]  C. Schmuck,et al.  Synthesis of glass-coated SERS nanoparticle probes via SAMs with terminal SiO2 precursors. , 2010, Small.

[6]  A. P. Chapman,et al.  PEGylated antibodies and antibody fragments for improved therapy: a review. , 2002, Advanced drug delivery reviews.

[7]  J L West,et al.  A whole blood immunoassay using gold nanoshells. , 2003, Analytical chemistry.

[8]  T. Allen,et al.  A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells. , 1995, Biochimica et biophysica acta.

[9]  D. Astruc,et al.  Gold Nanoparticles: Assembly, Supramolecular Chemistry, Quantum‐Size‐Related Properties, and Applications Toward Biology, Catalysis, and Nanotechnology. , 2004 .

[10]  E. Montserrat,et al.  Chronic lymphocytic leukemia. , 1995, The New England journal of medicine.

[11]  R. M. A. Sullan,et al.  Direct correlation of structures and nanomechanical properties of multicomponent lipid bilayers. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[12]  T. Allen,et al.  Insertion of poly(ethylene glycol) derivatized phospholipid into pre‐formed liposomes results in prolonged in vivo circulation time , 1996, FEBS letters.

[13]  L. Ginaldi,et al.  Levels of expression of CD19 and CD20 in chronic B cell leukaemias. , 1998, Journal of clinical pathology.

[14]  G. Schatz Theoretical Studies of Surface Enhanced Raman Scattering , 1984 .

[15]  Sebastian Schlücker,et al.  Multiplexing with SERS labels using mixed SAMs of Raman reporter molecules , 2009, Analytical and bioanalytical chemistry.

[16]  C. R. Martin,et al.  Size-Based Protein Separations in Poly(ethylene glycol)-Derivatized Gold Nanotubule Membranes , 2001 .

[17]  Gilbert C Walker,et al.  Photonic Nanoparticles for Cellular and Tissular Labeling , 2011 .

[18]  R. Weissleder A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[19]  Gilbert C. Walker,et al.  Phospholipid membrane encapsulation of nanoparticles for surface-enhanced Raman scattering. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[20]  Tamitake Itoh,et al.  Semiconductor quantum dots and metal nanoparticles: syntheses, optical properties, and biological applications , 2008, Analytical and bioanalytical chemistry.

[21]  Xiaohua Huang,et al.  Noble metals on the nanoscale: optical and photothermal properties and some applications in imaging, sensing, biology, and medicine. , 2008, Accounts of chemical research.

[22]  R. Murray,et al.  Nanometer Gold Clusters Protected by Surface-Bound Monolayers of Thiolated Poly(ethylene glycol) Polymer Electrolyte , 1998 .

[23]  Shuming Nie,et al.  Spectroscopic tags using dye-embedded nanoparticles and surface-enhanced Raman scattering. , 2003, Analytical chemistry.

[24]  Leon Hirsch,et al.  Gold nanoshell bioconjugates for molecular imaging in living cells. , 2005, Optics letters.

[25]  M. Hurme,et al.  Surface antigen expression in chronic lymphocytic leukemia: clustering analysis, interrelationships and effects of chromosomal abnormalities , 2002, Leukemia.

[26]  Gilbert C Walker,et al.  Detection of chronic lymphocytic leukemia cell surface markers using surface enhanced Raman scattering gold nanoparticles. , 2010, Cancer letters.

[27]  Thomas R Huser,et al.  Surface-enhanced Raman scattering from individual au nanoparticles and nanoparticle dimer substrates. , 2005, Nano letters.

[28]  J. Silvius,et al.  High-yield coupling of antibody Fab' fragments to liposomes containing maleimide-functionalized lipids. , 2004, Methods in enzymology.

[29]  F. Martin,et al.  Irreversible coupling of immunoglobulin fragments to preformed vesicles. An improved method for liposome targeting. , 1982, The Journal of biological chemistry.

[30]  J. Pendry,et al.  Collective Theory for Surface Enhanced Raman Scattering. , 1996, Physical review letters.

[31]  L. Johnston,et al.  Nanoscale imaging of domains in supported lipid membranes. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[32]  S. Nie,et al.  Single-Molecule and Single-Nanoparticle SERS: From Fundamental Mechanisms to Biomedical Applications , 2008 .