Abstract
Gold nanorods (NRs), rod-shaped gold nanoparticles, were modified with bovine serum albumin (BSA) and polyethylenimine (PEI) using layer-by-layer technique. From absorption spectroscopy and zeta potential measurements, it was obvious that NRs were wrapped with these polymers without aggregation of NRs. Following BSA modification, the surface-modified NRs (BSA-NRs) were well-dispersed without aggregation in biochemical conditions, verified from absorption spectroscopy. Further modification with PEI provided positively charged NRs (PEI-NRs). A transmission electron microscopy image of PEI-NRs revealed that the surface modification did not affect changing the shape of the initial NRs. In addition, the PEI-NRs retained the colloidal stability of BSA-NRs in biochemical conditions. We have evaluated that transfection activity of PEI-NRs with HeLa cells. From results of gene expression experiments, it was obvious that the stabilization of NRs by BSA and further modification with PEI realized transfection using NRs into cultured cells. Moreover, the cellular uptake of NRs enabled cellular imaging using light scattering from the NRs.
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
Introduction
The use of anisotropic materials for biological sensing and gene delivery has attracted great interest in the fields of materials science and bioscience (Martin and Kohli 2003; Bauer et al. 2004). Because of their elongated structure, anisotropic nanoparticles have chemical and optical anisotropy, and can interact with cells and biomolecules in fundamentally new ways. Anisotropic gold nanoparticles are also a topic of discussion at present (Sau and Murphy 2004). In particular, rod-shaped gold nanoparticles, gold nanorods (NRs), have attracted much attention as a new class of gold nanoparticles, due to their unique optical properties (Yu et al. 1997; Murphy et al. 2005; Pérez-Juste et al. 2005). NRs show two absorption peaks that correspond to the transverse and longitudinal surface plasmon (SP) bands in the visible region (∼520 nm) and the near-infrared (near-IR) region, respectively (Link et al. 1999; Brioude et al. 2005). The intense longitudinal SP band affords absorption (Gorelikov et al. 2004), fluorescence (Li et al. 2005), and light scattering (Lee and El-Sayed 2005; Alekseeva et al. 2005) in near-IR region.
Because near-IR light is a powerful tool for biochemical and biomedical applications (Loo et al. 2005; Hintersteiner et al. 2005), the unique near-IR properties of NRs are particularly expected to provide advantages for diagnostic and therapeutic fields. For example, the use of NRs and near-IR light enable in vitro and in vivo two-photon luminescence imaging (Wang et al. 2005). On the other hand, we demonstrated that near-IR laser irradiation realized controlled release of plasmid DNA from complexes of NRs and plasmid DNA (Takahashi et al. 2005). This is because pulsed near-IR laser irradiation provides reshaping of NRs into spherical nanoparticles (Link et al. 2000). This photoreaction could potentially be useful for a new type of gene delivery (Nishiyama et al. 2005). Thus, NRs are possible candidates for use as probes for cellular imaging and/or functional materials for gene delivery (Takahashi et al. 2005; Huang et al. 2006; Chen et al. 2006).
Various kinds of nanoparticles including NRs require biocompatibility and colloidal stability for biochemical and biomedical applications (Otsuka et al. 2003). In the case of NRs, a large amount of cationic detergent, hexadecyltrimethylammonium bromide (CTAB), is required as a stabilizing agent (Yu et al. 1997; Murphy et al. 2005; Pérez-Juste et al. 2005). On the other hand, the CTAB in NR solutions interferes with biological processes, and exhibits high cytotoxicity (Connor et al. 2005). To improve the biocompatibility of NRs, we previously succeeded in preparation of phosphatidylcoline (PC)-passivated NRs (PC-NRs) with very low cytotoxicity (Takahashi et al. 2006a, 2006b). Thus, PC-NR is expected to be a potential biomaterial; however, further modification is needed to obtain functional NRs for gene delivery because it is difficult to keep the NR’s well-dispersed, without aggregation in biochemical conditions (Takahashi et al. 2006c). To improve colloidal stability of gold nanoparticles in biochemical conditions, for example, surface modification with poly(ethylene glycol) (PEG) is a common strategy (Otsuka et al. 2003). We also reported in vivo stability of PEG-modified gold nanoparticles (Kawano et al. 2006) and gold nanorods (Niidome et al. 2006). On the other hand, Tkachenko et al. (2004) reported that bovine serum albumin (BSA) is useful for stabilizing nanoparticles under biochemical conditions. BSA modification provides simply biochemical stability via electrostatic interactions.
Layer-by-layer technique described by Decher (1997) allows nanoscale control over deposition of a large variety of functional materials through electrostatic interactions. Previously, Gole and Murphy (2005) reported that this technique is useful for altering the surface properties of NRs. In this study, the layer-by-layer technique was employed to modify PC-NRs with BSA and polyethylenimine (PEI). The surface modification of PC-NRs providing the colloidal stability realized transfection into cultured cells and cellular imaging using light scattering from the NRs.
Experimental
NRs, prepared with a slight modification of our method (Niidome et al. 2003), were supplied by Mitsubishi Materials Co. Ltd. The average length and width of the as-prepared NRs was +65 ± 5 nm and +11 ± 1 nm, respectively (aspect ratio: 5.9). The initial NR solution (∼1 mM (Au atoms)) contained 80 mM of CTAB. Some of the CTAB precipitated when the solution was kept in a refrigerator (∼4°C). The precipitated CTAB was removed by using a membrane filter (pore size, 0.8 μm). The residual CTAB in the NR solution (20 ml) was extracted into PC-chloroform solution (10 mg/ml, 10 ml; PC from egg yolk was purchased from Nacalai Tesque). After performing two more extraction procedures, the aqueous solutions containing NRs were centrifuged once, and then dispersed again in pure water (2 ml) (Takahashi et al. 2006a). Absorption spectra of the PC-NR solutions were measured with JASCO V-570. The zeta potentials of NRs were evaluated using a Zetasizer NanoZS (MALVERN, He–Ne laser). Zeta potential was calculated using a theoretical model with spherical particles. Thus, the value qualitatively indicates the sign and magnitude of the zeta potential of the NRs. This is sufficient for relative evaluation of the surface charge of NRs.
BSA aqueous solution (600 μl, 2 mg/ml) was added to 50 μl of PC-NR solution with stirring. After 15 min of incubation, the NR solution was centrifuged (6,500g, 10 min). The precipitated NRs were redispersed into 100 μl of water, and the resultant NR (BSA-NR) solution (50 μl) was added to 200 μl of PEI solution (25 kDa, 10 wt%) with stirring. The mixture was centrifuged after 15 min of incubation, and the precipitates were redispersed in 80 μl of water. The resultant NRs (PEI-NRs) were observed by transmission electron microscopy (TEM). To evaluate the colloidal stability of the modified NRs (BSA-NRs and PEI-NRs), absorption spectroscopic measurements were carried out. After the BSA addition to PC-NRs, the BSA-NRs were divided into two tubes, and were centrifuged. They were redispersed into water and PBS buffer, respectively. The BSA-NRs in water were mixed with the PEI solution, and were condensed by centrifugation. To compare the colloidal stability of the PEI-NRs in PBS buffer with that in water, the PEI-NRs were divided into two tubes, and were redispersed after further centrifugation in water and PBS buffer, respectively. Besides, the absorption spectrum of the PEI-NRs in PBS buffer was measured after 12 h.
For agarose gel electrophoresis, plasmid DNA containing the firefly luciferase reporter gene (Ohsaki et al. 2002) (7 kbp, 0.5 mg/ml, 10 μl) was mixed with various concentrations of the PEI-NR solutions (3.125–12.5 μM (Au atoms), 10 μl). After the addition of 10 μl of 5×TBE buffer and 20 μl of water, the mixed solutions were electrophoresed. The plasmid DNA was stained with SYBR® Green I (Molecular Probes).
HeLa cells were cultured in Dulbecco’s Modified Eagles Medium (DMEM) supplemented with 10% (v/v) of heat-inactivated fetal bovine serum (FBS) at 37°C, 5% CO2. The cells were plated at 5 × 103 cells/well in a 96-well plate, and incubated for 24 h. Cell viabilities of HeLa cells with PEI-NRs were estimated by a slight modification of the MTT assay (Takahashi et al. 2006a). Briefly, 10 μl of PEI-NR solution was added to the 100 μl of DMEM in each well (final NR concentrations: 0.25–1 μM). Following 24 h of incubation, 10 μl of Cell Counting Kit-8 (Dojindo Laboratories) was added to the medium. The absorbance of lysates after 2 h was measured at 450 nm by a 96-well microplate reader (Model 680 Microplate Reader, Bio-Rad Laboratories). To evaluate transfection efficiency for PEI-NR/DNA complexes, various concentrations (3.125–12.5 μM (Au atoms)) of PEI-NR solution (20 μl) were mixed with plasmid DNA (0.5 mg/ml, 20 μl), 10×PBS buffer and DMEM (final PEI-NR concentrations: 0.25–1 μM), and then the mixed solutions (250 μl) were poured gently onto the cells seeded as described above. After 3 h of incubation, the mixed solution was removed, and 250 μl of DMEM containing FBS was added to the well. After 48 h of incubation, luciferase assays were performed as described in the protocol of the Luciferase Assay System using a luminometer (Maltibiolumat LB9505, Berthold, Germany) (Niidome et al. 2004). The protein concentrations of the cell lysates were assessed with the Bradford assay (Protein Assay Kit, Bio-Rad).
For microscopic observation of the cultured cells treated with NRs, the cells were cultured in a glass base dish (50 mm, glass diameter: 12 mm) for 24 h. A PEI-NR/DNA complex solution and a PC-NR solution (final concentration: 1 μM) containing PBS and DMEM were poured into the dish. After 3 h of incubation, the solutions were removed, and fresh medium was poured into the dish. The near-IR light scattering images were obtained using a microscope (TE 2000, Nikon) equipped with a dark field condenser (T-CHA, Nikon), IR filter (HOYA R72) and CCD camera (NEPTUNE 100, Watec Co. Ltd.). All images were recorded with identical CCD gain and light illumination intensity.
Results and discussion
The effect of the surface modification of NRs on their colloidal stability can be evaluated from their absorption spectra, because SP bands of NRs depend sensitively on their colloidal stability. Absorption spectra of PC-NRs before and after the addition of BSA are shown in Fig. 1. An absorption spectrum of a PC-NR solution (0.5 mM) shows typical characteristics of a NR solution (Fig. 1A) (Link et al. 1999; Brioude et al. 2005). The zeta potential of the PC-NRs was +15 ± 1 mV (initial NRs: about +60 mV) (Takahashi et al. 2006a). After addition of BSA solution (600 μl, 2 mg/ml) to the PC-NR solution (50 μl), the absorption spectrum of the BSA-NRs (0.25 mM) (Fig. 1Ba) was the same as that of the PC-NR solution (Fig. 1A). This indicates that the resultant NRs formed no aggregates because an absorption spectrum of NR aggregates shows broader SP bands than that of well-dispersed NRs (Takahashi et al. 2005, 2006c). On the other hand, in the case of lower BSA/NRs ratio, the absorption spectrum of the PC-NRs showed remarkable change (not shown). This is due to formation of PC-NR aggregates by electrostatic interactions between PC-NR and BSA. Considering that the zeta potential of the well-dispersed NRs (Fig. 1Ba) was negative (−20 mV), it is obvious that BSA molecules wrapped the PC-NRs without inducing aggregation of PC-NRs. The spectrum of the BSA-NRs in PBS buffer (0.25 mM) (Fig. 1Bb) was the same as that in water (Fig. 1Ba), despite PC-NRs form small aggregates in PBS buffer (Takahashi et al. 2006c). These suggested that BSA modification provided the colloidal stability in biochemical conditions to PC-NRs.
Figure 2a shows absorption spectrum of the PEI-NRs (0.25 mM) in water. When 50 μl the BSA-NR solution was added to 200 μl PEI solution (25 kDa, 10 wt%), the zeta potential of the PEI-NRs changed to positive (+8 mV). While this indicated that PEI molecules interacted with BSA-NRs, the absorption spectrum in Fig. 2a was identical to that of BSA-NRs (Fig. 1B), indicating the absence of NR aggregates. These suggested that BSA-NRs were modified with PEI without aggregation. A TEM image of the PEI-NRs is shown in Fig. 2b. The average length and width of the PEI-NRs are the same as those of as-prepared NRs. From these results, it was confirmed that the surface modification using the layer-by-layer approach gave positively charged NRs without changing the shape of the initial NRs.
Figure 3 shows absorption spectra of PEI-NRs (0.125 mM) in PBS buffer. The two curves in Fig. 3 indicate that the PEI-NRs were well-dispersed in PBS buffer for at least 12 h. Considering that PC-NRs form small aggregates in PBS buffer (Takahashi et al. 2006c), it is obvious that the addition of PEI did not induce BSA dissociation from the PC-NR surface. Thus, the BSA-NR was wrapped with PEI molecules and retained the colloidal stability in PBS buffer after the PEI modification. Gole and Murphy (2005) reported that a delicate balance of several parameters (the polymer type, concentration, chain length, and so on) is essential for preventing aggregation of NRs and achieving coating with polymers. In our study, the use of larger PEI (for example, 750 kDa) or higher NR concentrations than described above induced aggregation of NRs. To obtain desirable NRs, the balance described above are essential in this study.
In Fig. 4, the electrophoretic patterns of the plasmid DNA without (a) and with (b–d) PEI-NR solution are shown. The amount of migrating DNA decreased with increasing PEI-NR concentration. When 3.125 μM of PEI-NR solution was added to the DNA solution (b), a relatively small amount of the plasmid DNA migrated. Fluorescence around the well of lane (b) indicates that some of the plasmid DNA remains in the well even after electrophoresis. Addition of 6.25 μM (c) and 12.5 μM (d) of PEI-NR solutions completely suppressed the migration of the plasmid DNA. Thus, the electrophoretic patterns indicate the formation of PEI-NR/DNA complexes.
Gene expression on addition of PEI-NR/DNA complexes to cultured cells is shown in Fig. 5 (bars). Transfection efficiency has improved by formation of the complexes. When plasmid DNA formed complexes with 12.5 μM PEI-NR (final PEI-NR concentration in medium: 1 μM), the transfection efficiency was about 40 times higher than that of naked DNA. When PEI-NRs were precipitated by centrifugation (6,500g, 10 min), the supernatant showed no enhancement of gene expression under the same experimental condition. Thus, it was obvious that the gene expression in Fig. 5 resulted from PEI-NR/DNA complexes. In addition, under these transfection conditions, the PEI-NR/DNA complexes showed negligible cytotoxicity (line in Fig. 5). It was remarkable that the PEI (25 kDa) showed such low cytotoxicity. High molecular weight PEIs (>2,000 Da) frequently show high cytotoxicity in return for higher transfection activity (Alexis et al. 2006; Tang et al. 2006). When lower molecular weight PEI (for example, 800 Da) was used for the layer-by-layer deposition, the resultant PEI-modified NRs showed no transfection activity. PC-NRs also showed no transfection despite PC-NRs formed complexes with plasmid DNA and interacted with cultured cells (Takahashi et al. 2005, 2006a). To achieve gene delivery using the surface-modified NRs, the “balance” of several parameters (cytotoxicity, colloidal dispersion, cellular uptake efficiency, etc.) must be optimized. The surface modification with BSA and PEI gave a balanced surface condition to achieve efficient transfection without inducing cell death. Thus, PEI-NRs can be used as a transfection vehicle for in vitro gene delivery.
The unique optical property of NRs enables light scattering imaging (Orendorff et al. 2006; Huang et al. 2006). Figure 6 shows microscopic images (A–C) and near-IR light scattering images (D–F) of HeLa cells in the absence and presence of two kinds of NRs (PEI-NRs, PC-NRs). In the absence of NRs (A), hardly any scattered light was observed from HeLa cells (D). This means that scattered light from the cell organelles and membrane was negligible under the experimental conditions used. In the presence of PEI-NR/DNA complexes (B), the cell image could be seen by scattered light (E). This indicates that the PEI-NRs were accumulated in and/or on the cells, to make individual cells identifiable (El-Sayed et al. 2005). In the presence of PC-NRs (C), the light scattering was much weaker than in the presence of PEI-NRs (F), in spite of the same amount of NR being used as for the case in (E). This indicates that the surface modification increased cellular binding and uptake, resulting in the transfection activity of the NRs.
Conclusion
This is a preliminary work realizing gene delivery using surface-modified NRs. A layer-by-layer technique had achieved the surface modification of PC-NRs with BSA and PEI without forming aggregation. The surface-modified NRs with high colloidal stability retained the near-IR property in biochemical conditions and showed cellular uptake activity. The transfection efficiency was smaller than that of PEI/DNA complexes (Boussif et al. 1995; Godbey et al. 1999; Kursa et al. 2003). Thus, further development to achieve a “fine-tuned” surface is needed; however, NRs having uptake activity is advantageous to biochemical and biomedical applications using the near-IR region. For example, use of near-IR light realizes controlled release of plasmid DNA from NR/DNA complexes (Takahashi et al. 2005). If the photoreaction can be used for gene delivery, gene expression will be enhanced by near-IR light. Such a photochemical enhancement system could be useful for a new type of gene delivery system. Moreover, near-IR scattering imaging was advantageous in monitoring the distribution of NRs in living cells without use of fluorescent molecules, which tend to be quenched by the intense excitation light required for microscopic fluorescent observation. Surface-modified NRs with a fine-tuned surface will open up a new type of gene delivery and probing system.
References
Alekseeva AV, Bogatyrev VA, Dykman LA, Khlebtsov BN, Trachuk LA, Melnikov AG, Khlebtsov NG (2005) Preparation and optical scattering characterization of gold nanorods and their application to a dot-immunogold assay. Appl Optics 44:6285–6295
Alexis F, Lo S-L, Wang S (2006) Covalent attachment of low molecular weight poly(ethylene imine) improves Tat peptide mediated gene delivery. Adv Mater 18:2174–2178
Bauer LA, Birenbaum NS, Meyer GJ (2004) Biological applications of high aspect ratio nanoparticles. J Mater Chem 14:517–526
Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr J-P (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci USA 92:7297–7301
Brioude A, Jiang XC, Pileni MP (2005) Optical properties of gold nanorods: DDA simulations supported by experiments. J Phys Chem B 109:13138–13142
Chen C-C, Lin Y-P, Wang C-W, Tzeng H-C, Wu C-H, Chen Y-C, Chen C-P, Chen L-C, Wu Y-C (2006) DNA-gold nanorod conjugates for remote control of localized gene expression by near infrared irradiation. J Am Chem Soc 128:3709–3715
Connor EE, Mwamuka J, Gole A, Murphy CJ, Wyatt MD (2005) Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. Small 1:325–327
Decher G (1997) Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 277:1232–1237
El-Sayed IH, Huang X, El-Sayed MA (2005) Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: applications in oral cancer. Nano Lett 5:829–834
Godbey WT, Wu KK, Mikos AG (1999) Poly(ethylenimine) and its role in gene delivery. J Control Release 60:149–160
Gole A, Murphy CJ (2005) Polyelectrolyte-coated gold nanorods: synthesis, characterization and immobilization. Chem Mater 17:1325–1330
Gorelikov I, Field LM, Kumacheva E (2004) Hybrid microgels photoresponsive in the near-infrared spectral range. J Am Chem Soc 126:15938–15939
Hintersteiner M, Enz A, Frey P, Jaton A-L, Kinzy W, Kneuer R, Neumann U, Rudin M, Staufenbiel M, Stoeckli M, Wiederhold K-H, Gremlich H-U (2005) In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probe. Nat Biotechnol 23:577–583
Huang X, El-Sayed IH, Qian W, El-Sayed MA (2006) Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. J Am Chem Soc 128:2115–2120
Kawano T, Yamagata M, Takahashi H, Niidome Y, Yamada S, Katayama Y, Niidome T (2006) Stabilizing of plasmid DNA in vivo by PEG-modified cationic gold nanoparticles and the gene expression assisted with electrical pulses. J Control Release 111:382–389
Kursa M, Walker GF, Roessler V, Ogris M, Roedl W, Kircheis R, Wagner E (2003) Novel shielded transferrin-polyethylene glycol-polyethylenimine/DNA complexes for systemic tumor-targeted gene transfer. Bioconjugate Chem 14:222–231
Lee K-S, El-Sayed MA (2005) Dependence of the enhanced optical scattering efficiency relative to that of absorption for gold metal nanorods on aspect ratio, size, end-cap shape, and medium refractive index. J Phys Chem B 109:20331–20338
Li C-Z, Male KB, Hrapovic S, Luong JHT (2005) Fluorescence properties of gold nanorods and their application for DNA biosensing. Chem Commun 3924–3926
Link S, Mohamed MB, El-Sayed MA (1999) Simulation of the optical absorption spectra of gold nanorods as a function of their aspect ratio and the effect of the medium dielectric constant. J Phys Chem B 103:3073–3077
Link S, Mohamed MB, El-Sayed MA (2000) Laser-induced shape changes of colloidal gold nanorods using femtosecond and nanosecond laser pulses. J Phys Chem B 104:6152–6163
Loo C, Lowery A, Halas N, West J, Drezek R (2005) Immunotargeted nanoshells for integrated cancer imaging and therapy. Nano Lett 5:709–711
Martin CR, Kohli P (2003) The emerging field of nanotube biotechnology. Nat Rev Drug Discov 2:29–37
Murphy CJ, Sau TK, Gole AM, Orendorff CJ, Gao J, Gou L, Hunyadi SE, Li T (2005) Anisotropic metal nanoparticles: synthesis, assembly, and optical applications. J Phys Chem B 109:13857–13870
Niidome T, Nakashima K, Takahashi H, Niidome Y (2004) Preparation of primary amine-modified gold nanoparticles and their transfection ability into cultured cells. Chem Commun 1978–1979
Niidome T, Yamagata M, Okamoto Y, Akiyama Y, Takahashi H, Kawano T, Katayama Y, Niidome Y (2006) PEG-modified gold nanorods with a stealth character for in vivo applications. J Control Release 114:343–347
Niidome Y, Nishioka K, Kawasaki H, Yamada S (2003) Rapid synthesis of gold nanorods by the combination of chemical reduction and photoirradiation processes; morphological changes depending on the growing processes. Chem Commun 2376–2377
Nishiyama N, Iriyama A, Jang W-D, Miyata K, Itaka K, Inoue Y, Takahashi H, Yanagi Y, Tamaki Y, Koyama H, Kataoka K (2005) Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer. Nat Mater 4:934–941
Ohsaki M, Okuda T, Wada A, Hirayama T, Niidome T, Aoyagi H (2002) In vitro gene transfection using dendritic poly(L-lysine). Bioconjugate Chem 13:510–517
Orendorff CJ, Sau TK, Murphy CJ (2006) Shape-dependent plasmon-resonant gold nanoparticles. Small 2:636–639
Otsuka H, Nagasaki Y, Kataoka K (2003) PEGylated nanoparticles for biological and pharmaceutical applications. Adv Drug Deliv Rev. 55:403–419
Pérez-Juste J, Pastoriza-Santos I, Liz-Marzán LM, Mulvaney P (2005) Gold nanorods: synthesis, characterization and applications. Coordin Chem Rev 249:1870–1901
Sau TK, Murphy CJ (2004) Room temperature, high-yield synthesis of multiple shapes of gold nanoparticles in aqueous solution. J Am Chem Soc 126:8648–8649
Takahashi H, Niidome Y, Yamada S (2005) Controlled release of plasmid DNA from gold nanorods induced by pulsed near-infrared light. Chem Commun 2247–2249
Takahashi H, Niidome Y, Niidome T, Kaneko K, Kawasaki H, Yamada S (2006a) Modification of gold nanorods using phosphatidylcholine to reduce cytotoxicity. Langmuir 22:2–5
Takahashi H, Niidome T, Nariai A, Niidome Y, Yamada S (2006b) Gold nanorod-sensitized cell death: microscopic observation of single living cells irradiated by pulsed near-infrared laser light in the presence of gold nanorods. Chem Lett 35:500–501
Takahashi H, Niidome T, Nariai A, Niidome Y, Yamada S (2006c) Photothermal reshaping of gold nanorods prevents further cell death. Nanotechnology 17:4431–4435
Tang GP, Guo HY, Alexis F, Wang X, Zeng S, Lim TM, Ding J, Yang YY, Wang S (2006) Low molecular weight polyethylenimines linked by β-cyclodextrin for gene transfer into the nervous system. J Gene Med 8:736–744
Tkachenko AG, Xie H, Liu Y, Coleman D, Ryan J, Glomm WR, Shipton MK, Franzen S, Feldheim DL (2004) Cellular trajectories of peptide-modified gold particle complexes: comparison of nuclear localization signals and peptide transduction domains. Bioconjugate Chem 15:482–490
Wang H, Huff TB, Zweifel DA, He W, Low PS, Wei A, Cheng J-X (2005) In vitro and in vivo two-photon luminescence imaging of single gold nanorods. Proc Natl Acad Sci USA 102:15752–15756
Yu Y-Y, Chang S-S, Lee C-L, Wang CRC (1997) Gold nanorods: electrochemical synthesis and optical properties. J Phys Chem B 101:6661–6664
Acknowledgments
This study was supported in part by Research Fellowships of the Japan Society for Promotion of Science (JSPS) for Young Scientists, and by a Grant-in-Aid for Scientific Research (KAKENHI) in the Priority Area “Molecular Nano Dynamics” from the Ministry of Education, Culture, Sports, Science and Technology.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Takahashi, H., Niidome, T., Kawano, T. et al. Surface modification of gold nanorods using layer-by-layer technique for cellular uptake. J Nanopart Res 10, 221–228 (2008). https://doi.org/10.1007/s11051-007-9227-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11051-007-9227-5