- Label-free imaging of semiconducting and metallic carbon nanotubes in cells and mice using transient absorption microscopy Nature Nanotechnology ; accepted
- Color switch and three photon luminescence in doped colloidal quantum rods J. Am. Chem. Soc 2011; 133: 5389
- Label-free imaging through nonlinear optical signals Materials Today 2011; 14: 262
- Bright Three-Photon Luminescence from Gold/Silver Alloyed Nanostructures for Bioimaging with Negligible Photothermal Toxicity ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 2010; 49 (20): 3485-3488
Visualizing Systemic Clearance and Cellular Level Biodistribution of Gold Nanorods by Intrinsic Two-Photon Luminescence
2009; 25 (21): 12454-12459
Characterization of systemic performance of gold nanostructures is critical to the advancement of biomedical applications of these nanomaterials as imaging or therapeutic agents. The accuracy of current in vitro methods, however, is limited by interanimal variability. We present a novel method capable of monitoring the pharmacokinetics of PEGylated gold nanorods (GNRs) in the same animal by using intravital two-photon luminescence (TPL) imaging of GNRs flowing through a surface blood vessel. The TPL imaging with high speed and submicrometer resolution allowed for studying the clearance of GNRs as a function of surface coating. PEGylated-GNRs (PEG-NRs) were found to exhibit a biphasic clearance mode, with a significantly prolonged blood residence time for branched poly(ethylene glycol) (PEG) as compared to the linear PEG. With spectral detection to distinguish GNR TPL from tissue autofluorescence, we also mapped the cellular distribution of GNRs in the explanted organs, and found most GNRs resided in the macrophages in liver and spleen.
View details for DOI 10.1021/la902992w
View details for Web of Science ID 000271106600012
View details for PubMedID 19856987
In Vitro and In Vivo Nonlinear Optical Imaging of Silicon Nanowires
2009; 9 (6): 2440-2444
Understanding of cellular interactions with a nanostructure requires tracking directly the nanostructure. Current investigation is challenged by the lack of a strong, intrinsic signal from the nanostructure. We demonstrate intensive four-wave mixing and third-harmonic generation signals from dimension-controllable silicon nanowires as small as 5 nm in diameter. The nonlinear optical signals observed from the nanowires are highly photostable with an intensity level of 10 times larger than that observed from silver nanoparticles of comparable sizes. This intrinsic optical signal enabled intravital imaging of nanowires circulating in the peripheral blood of a mouse and mapping of nanowires accumulated in the liver and spleen, opening up further opportunities to investigate in vivo cellular response to nanomaterials as a function of size, aspect ratio, and surface chemistry.
View details for DOI 10.1021/nl901143p
View details for Web of Science ID 000266969400044
View details for PubMedID 19507891
Gold nanorod-mediated photothermolysis induces apoptosis of macrophages via damage of mitochondria
2009; 4 (3): 265-276
Induction of apoptosis or necrosis in activated macrophages by gold nanorod-mediated photothermolysis is demonstrated and the mechanisms underlying the processes are investigated.Gold nanorods were functionalized with cysteine-octaarginine peptides (R8-NRs). Uptake of R8-NRs by activated macrophages was monitored by two-photon luminescence imaging. The laser irradiation conditions were controlled to induce apoptosis or necrosis to R8-NR-internalized macrophages. Mitochondrial damage and reactive oxygen species overproduction during photothermolysis was investigated by confocal fluorescence microscopy and transmission-electron microscopy.Activated macrophages efficiently uptake R8-NRs both in vitro and in live animals. Laser irradiation of internalized nanorods with controlled power density induces apoptosis of macrophages via intracellular perturbation and subsequent injury of mitochondria.Gold nanorod-mediated photothermolysis provides one promising way to eliminate activated macrophages in autoimmune and inflammatory diseases.
View details for DOI 10.2217/NNM.09.4
View details for Web of Science ID 000265162200008
View details for PubMedID 19331536
Intracellular Drug Delivery by Poly(lactic-co-glycolic acid) Nanoparticles, Revisited
2009; 6 (1): 190-201
We reexamined the cellular drug delivery mechanism by poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) to determine their utility and limitations as an intracellular drug delivery system. First, we prepared PLGA NPs which physically encapsulated Nile red (a hydrophobic fluorescent dye), in accordance with the usual procedure for labeling PLGA NPs, incubated them with mesothelial cells, and observed an increase in the intracellular fluorescence. We then prepared NPs from PLGA chemically conjugated to a fluorescent dye and observed their uptake by the mesothelial cells using confocal microscopy. We also used coherent anti-Stokes Raman scattering (CARS) microscopy to image cellular uptake of unlabeled PLGA NPs. Results of this study coherently suggest that PLGA NPs (i) are not readily taken up by cells, but (ii) deliver the payload to cells by extracellular drug release and/or direct drug transfer to contacting cells, which are contrasted with the prevalent view. From this alternative standpoint, we analyzed cytotoxicities of doxorubicin and paclitaxel delivered by PLGA NPs and compared with those of free drugs. Finally, we revisit previous findings in the literature and discuss potential strategies to achieve efficient drug delivery to the target tissues using PLGA NPs.
View details for DOI 10.1021/mp800137z
View details for Web of Science ID 000263035000020
View details for PubMedID 19035785
Gold Nanorods as Contrast Agents for Biological Imaging: Optical Properties, Surface Conjugation and Photothermal Effects
PHOTOCHEMISTRY AND PHOTOBIOLOGY
2009; 85 (1): 21-32
Gold nanorods (NRs) have plasmon-resonant absorption and scattering in the near-infrared (NIR) region, making them attractive probes for in vitro and in vivo imaging. In the cellular environment, NRs can provide scattering contrast for darkfield microscopy, or emit a strong two-photon luminescence due to plasmon-enhanced two-photon absorption. NRs have also been employed in biomedical imaging modalities such as optical coherence tomography or photoacoustic tomography. Careful control over surface chemistry enhances the capacity of NRs as biological imaging agents by enabling cell-specific targeting, and by increasing their dispersion stability and circulation lifetimes. NRs can also efficiently convert optical energy into heat, and inflict localized damage to tumor cells. Laser-induced heating of NRs can disrupt cell membrane integrity and homeostasis, resulting in Ca(2+) influx and the depolymerization of the intracellular actin network. The combination of plasmon-resonant optical properties, intense local photothermal effects and robust surface chemistry render gold NRs as promising theragnostic agents.
View details for DOI 10.1111/j.1751-1097.2008.00507.x
View details for Web of Science ID 000262486800003
View details for PubMedID 19161395
- Imaging gold nanorods by plasmon-resonance-enhanced four wave mixing J. Phys. Chem. C 2009; 113: 2657
Imaging receptor-mediated endocytosis with a polymeric nanoparticle-based coherent anti-stokes raman scattering probe
JOURNAL OF PHYSICAL CHEMISTRY B
2007; 111 (33): 9980-9985
Coherent anti-Stokes Raman scattering (CARS) microscopy was used to visualize receptor-mediated endocytosis and intracellular trafficking with the aid of a CARS probe. The probe was made of 200-nm polystyrene particles encapsulated in folate-targeted liposomes. By tuning (omega(p) - omega(s)) to 3045 cm(-1), which corresponds to the aromatic C-H stretching vibration, the polystyrene nanoparticles with a high density of aromatic C-H bonds were detected with a high signal-to-noise ratio, while the epi-detected CARS signal from cellular organelles was cancelled by the destructive interference between the resonant contribution from the aliphatic C-H vibration and the nonresonant contribution. Without any photobleaching, the CARS probe allowed single-particle tracking analysis of intracellular endosome transport. No photodamage to cells was observed under the current experimental conditions. These results show the advantages and potential of using a CARS probe to study cellular processes.
View details for DOI 10.1021/jp073478z
View details for Web of Science ID 000248759000038
View details for PubMedID 17663581
Hyperthermic effects of gold nanorods on tumor cells
Symposium on Advances in Nanomedicine held at the 233rd National American-Chemical-Society Meeting
FUTURE MEDICINE LTD. 2007: 125?32
Plasmon-resonant gold nanorods, which have large absorption cross sections at near-infrared frequencies, are excellent candidates as multifunctional agents for image-guided therapies based on localized hyperthermia. The controlled modification of the surface chemistry of the nanorods is of critical importance, as issues of cell-specific targeting and nonspecific uptake must be addressed prior to clinical evaluation. Nanorods coated with cetyltrimethylammonium bromide (a cationic surfactant used in nanorod synthesis) are internalized within hours into KB cells by a nonspecific uptake pathway, whereas the careful removal of cetyltrimethylammonium bromide from nanorods functionalized with folate results in their accumulation on the cell surface over the same time interval. In either case, the nanorods render the tumor cells highly susceptible to photothermal damage when irradiated at the nanorods' longitudinal plasmon resonance, generating extensive blebbing of the cell membrane at laser fluences as low as 30 J/cm2.
View details for DOI 10.2217/174358126.96.36.199
View details for Web of Science ID 000244350100017
View details for PubMedID 17716198
- Plasmon-resonant nanorods as multimodal agents for two-photon luminescence imaging and photothermal therapy Proc. SPIE 2007; 6448: 11
- Gold nanorods mediate tumor cell death by compromising membrane integrity Advanced Materials 2007; 19: 3136