Lab-on-Fiber Sensors with Ag/Au Nanocap Arrays Based on the Two Deposits of Polystyrene Nanospheres.

Surface-enhanced Raman spectroscopy (SERS) can boost the pristine Raman signal significantly which could be exploited for producing innovative sensing devices with advanced properties. However, the inherent complexity of SERS systems restricts their further applications in rapid detection, especially in situ detection in narrow areas. Here, we construct an efficient and flexible SERS-based Lab-on-Fiber (LOF) sensor by integrating Ag/Au nanocap arrays obtained by Ag/Au coating polystyrene nanospheres on the optical fiber face. We obtain rich "hot spots" at the nanogaps between neighboring nanocaps, and further achieve SERS performance with the assistance of laser-induced thermophoresis on the metal film that can achieve efficiency aggregation of detected molecules. We achieve a high Raman enhancement with a low detection limitation of 10-7 mol/L for the most efficient samples based on the above sensor. This sensor also exhibits good repeatability and stability under multiple detections, revealing the potential application for in situ detection based on the reflexivity of the optical fiber.

Ion irradiation of monolayer graphene-Nd:YAG hybrid waveguides: fabrication and laser.

Hybrid waveguides consisting of two-dimensional layered materials pad on the surface of optical waveguides suffer from a nonuniform and loose contact between the two-dimensional material and the waveguide, which can reduce the efficiency of the pulsed laser. Here, we present high-performance passively Q-switched pulsed lasers in three distinct structures of monolayer graphene-Nd:YAG hybrid waveguides irradiated by energetic ions. The ion irradiation enables the monolayer graphene a tight contact and strong coupling with the waveguide. As a result, Q-switched pulsed lasers with narrow pulse width and high repetition rate are obtained in three designed hybrid waveguides. The narrowest pulse width is 43.6 ns, provided by the ion-irradiated Y-branch hybrid waveguide. This study paves the way toward developing on-chip laser sources based on hybrid waveguides by using ion irradiation.

Tribological Properties and Lubrication Mechanisms of Water-Based Nanolubricants Containing TiO2 Nanoparticles during Micro Rolling of Titanium Foils.

The tribological behavior of traditional oil-in-water (O/W) lubricants (1.0 wt.%) and nano-TiO2 additive lubricants (1.0-9.0 wt.%) during micro rolling of titanium foils were analyzed. In this study, the surface morphologies of titanium foils under various lubrication conditions were assessed, and the corresponding lubrication mechanisms were revealed. The tribological behavior of nano-TiO2 additive lubricants during micro rolling of titanium foils was also explored through a series of characterization methods. The utilization of nano-TiO2 additive lubricants in micro rolling reduces the surface roughness of titanium foils. Moreover, it effectively inhibits the generation of indentations and cracks during rolling processes, enhancing the surface quality of rolled specimens. Additionally, owing to the synergism of rolling, tribo-film, mending and polishing effects of the nanoparticles, both the rolling force and surface roughness were minimized by using lubricants containing 3.0 wt.% TiO2 nanoparticles. Overall, an optimal concentration (3.0 wt.%) of TiO2 nanoparticles in water-based nanolubricants was obtained with enhanced tribological properties and lubrication performance during micro rolling of titanium foils.

Study on the Tribological Behaviour of Nanolubricants during Micro Rolling of Copper Foils.

Water-based lubricants with different fractions of TiO2 nanoparticles ranging from 1.0 to 9.0 wt.% were utilized to study the lubrication mechanisms during micro rolling tests and the tribological behaviour of nanolubricants during the micro rolling of copper foils. The results indicate that the application of TiO2 nanolubricants remarkably improves the surface quality of rolled copper foils during rolling processes. For lubricants with inadequate TiO2 nanoparticles, it is found that few TiO2 nanoparticles enter the contact regions between the rolls and foils, causing insufficient lubrication during rolling processes. Instead, for lubricants with excessive TiO2 nanoparticles, obvious agglomeration occurs at the contact regions and promotes the generation of voids on the surface of the rolled foils, thereby deteriorating the surface quality of the rolled copper foils. In addition, it is found that the surface quality of rolled foils is improved by utilizing a large reduction ratio. Overall, the fraction of 3.0 wt.% TiO2 nanolubricants is optimal to improve the lubrication conditions at the contact regions, thereby improving the surface quality of the rolled copper foils.

Characteristics of indoor and outdoor fine particles in heating period at urban, suburban, and rural sites in Harbin, China.

Concurrent indoor-outdoor fine particulate matter (PM2.5) measurements were conducted at urban, suburban, and rural sites in Harbin, a megacity in the northeast of China. Chemical constituents of indoor-outdoor PM2.5 were determined. Infiltration factors (FINF) of all sites were calculated according to the indoor to outdoor (I/O) ratios of PM2.5 based on the regression analysis. Linear discriminant analysis (LDA) is applied to determine the indoor-outdoor relationship. Secondary organic carbon (SOC) was calculated on the basis of organic carbon to elemental carbon (OC/EC) ratios. The mean concentrations of indoor and outdoor PM2.5 were 166.4 ± 32.5 µg/m3 and 228.4 ± 83.7 µg/m3, respectively, during the heating period. OC/EC and potassium ion to elemental carbon (K+/EC) ratios verified that biomass was an important source in Harbin especially for rural sites. The nitrate to sulfate (NO3-/SO42-) ratio indicates the higher contribution of traffic emissions in urban sites. Cr was the only species that exceeded the guidelines of WHO 2002, which was mainly emitted from coal and oil combustion. SOC/OC and NO3-/SO42- ratios, and ion-balanced acidity (the ratio of cation to anion, R+/-) showed a large urban-rural and indoor-outdoor difference. The highest SOC/OC ratio was found at urban sites, up to 38.3% for indoors. SOC/OC ratios and R+/- values of indoor environments were higher, which is attributed to the conducive condition of forming the secondary pollutants during the heating period. The results of LDA indicated that the distributions of the chemical components of PM2.5 at three sites were statistically dissimilar. Graphical abstract.

Two-Dimensional Heterostructure as a Platform for Surface-Enhanced Raman Scattering.

Raman enhancement on a flat nonmetallic surface has attracted increasing attention, ever since the discovery of graphene enhanced Raman scattering. Recently, diverse two-dimensional layered materials have been applied as a flat surface for the Raman enhancement, attributed to different mechanisms. Looking beyond these isolated materials, atomic layers can be reassembled to design a heterostructure stacked layer by layer with an arbitrary chosen sequence, which allows the flow of charge carriers between neighboring layers and offers novel functionalities. Here, we demonstrate the heterostructure as a novel Raman enhancement platform. The WSe2 (W) monolayer and graphene (G) were stacked together to form a heterostructure with an area of 10 mm × 10 mm. Heterostructures with different stacked structuress are used as platforms for the enhanced Raman scattering, including G/W, W/G, G/W/G/W, and W/G/G/W. On the surface of the heterostructure, the intensity of the Raman scattering is much stronger compared with isolated layers, using the copper phthalocyanine (CuPc) molecule as a probe. It is found that the Raman enhancement effect on heterostructures depends on stacked methods. Phonon modes of CuPc have the strongest enhancement on G/W. W/G and W/G/G/W have a stronger enhancement than that on the isolated WSe2 monolayer, while lower than the graphene monolayer. The G/W/G/W/substrate demonstrated a comparable Raman enhancement effect than the G/W/substrate. These differences are due to the different interlayer couplings in heterostructures related to electron transition probability rates, which are further proved by first-principle calculations and probe-pump measurements.

Electrically Tunable Nd:YAG waveguide laser based on Graphene.

We demonstrate a tunable hybrid Graphene-Nd:YAG cladding waveguide laser exploiting the electro-optic and the Joule heating effects of Graphene. A cladding Nd:YAG waveguide was fabricated by the ion irradiation. The multi-layer graphene were transferred onto the waveguide surface as the saturable absorber to get the Q-switched pulsed laser oscillation in the waveguide. Composing with appropriate electrodes, graphene based capacitance and heater were formed on the surface of the Nd:YAG waveguide. Through electrical control of graphene, the state of the hybrid waveguide laser was turned on or off. And the laser operation of the hybrid waveguide was electrically tuned between the continuous wave laser and the nanosecond pulsed laser.

Q-switched waveguide laser based on two-dimensional semiconducting materials: tungsten disulfide and black phosphorous.

Owing to their unique properties, graphene-like two dimensional semiconducting materials, including Tungsten Disulfide (WS2) and Black Phosphorous (BP), have attracted increasing interest from basic research to practical applications. Herein, we demonstrated the ultrafast nonlinear saturable absorption response of WS2 and BP films in the waveguide structure. Through fabricating WS2 and BP films by evaporating the solutions on glass wafers. Saturable absorber films were attached onto the end-facet of the waveguide, which therefore constitutes a resonant cavity for the waveguide laser. Under a pump laser at 810 nm, we could obtain a stable Q-switched operation in the waveguide structure. This work indicated the significant potential of WS2 and BP for the ultrafast waveguide laser.

Biocompatibility assessment of porous chitosan-Nafion and chitosan-PTFE composites in vivo.

Chitosan (CS) is widely used as a scaffold material in tissue engineering. The objective of this study was to test whether porous chitosan membrane (PCSM) coating for Nafion used in implantable sensor reduced fibrous capsule (FC) density and promoted superior vascularization compared with PCSM coating for polytetrafluoroethylene (PTFE). PCSM was fabricated with solvent casting/particulate leaching method using silica gel as porogen and characterized in vitro. Then, PCSM-Nafion and PCSM-PTFE composites were assembled with hydrated PCSM and implanted subcutaneously in rats. The histological analysis was performed in comparison with Nafion and PTFE. Implants were explanted 35, 65, and 100 days after the implantation. Histological assessments indicated that both composites achieved presumed effects of porous coatings on decreasing collagen deposition and promoting angiogenesis. PCSM-PTFE exerted higher collagen deposition by area ratio, both within and outside, compared with that of PCSM-Nafion. Angiogenesis within and outside the PCSM-Nafion both increased over time, but that of the PCSM-PTFE within decreased.

Quality of life appears similar between survivors of indolent and aggressive non-Hodgkin lymphoma.

Few studies have examined the quality of life (QOL) in survivors of non-Hodgkin lymphoma (NHL). A total of 109 patients with NHL (58 aggressive [AGG], 51 indolent [IND]) completed two health-related QOL assessments using the Medical Outcomes Study 36-Item Short-Form Healthy Survey (MOS SF-36) and the Functional Assessment in Cancer Therapy - Fatigue (FACT-F). Scores between IND and AGG were compared using a two-sample t-test. Multiple linear regression was performed to account for any potentially explanatory variables. Overall, 70.6% had received chemotherapy and 55% had received immunotherapy. Some 17.6% of the IND group had received no therapy. The overall physical and mental component QOL scores of the SF-36 did not differ between survivors. Physical function in survivors of IND was significantly better when compared with that of AGG NHL. Our study reports a similar overall QOL between survivors of IND and AGG NHL. Physical function, however, may be more impaired in survivors of AGG NHL.

Injectable sustained release microparticles of curcumin: a new concept for cancer chemoprevention.

Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and biocompatible polymer, poly(d,l-lactide-co-glycolide), was used to fabricate curcumin microparticles. When injected s.c. in mice, a single dose of microparticles sustained curcumin levels in the blood and other tissues for nearly a month. Curcumin levels in the lungs and brain, frequent sites of breast cancer metastases, were 10- to 30-fold higher than that in the blood. Further, curcumin microparticles showed marked anticancer efficacy in nude mice bearing MDA-MB-231 xenografts compared with other controls. Repeated systemic injections of curcumin were not effective in inhibiting tumor growth. Treatment with curcumin microparticles resulted in diminished vascular endothelial growth factor expression and poorly developed tumor microvessels, indicating a significant effect on tumor angiogenesis. These results suggest that sustained delivery of chemopreventives such as curcumin using polymeric microparticles is a promising new approach to cancer chemoprevention and therapy.

4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies.

Umbilical cord blood (UCB) T cells can be redirected to kill leukemia and lymphoma cells by engineering with a single-chain chimeric antigen receptor (CAR) and thus may have general applications in adoptive cell therapy. However, the role of costimulatory molecules in UCB T-cell activation and effector functions in context with CAR remains elusive. To investigate the effect of costimulatory molecules (4-1BB and CD28) on UCB T cells, we transduced UCB T cells with lentiviral vectors expressing Green Fluorescent Protein (GFP) and CAR for CD19 containing an intracellular domain of the CD3zeta chain and either a 4-1BB (UCB-19BBzeta) or a CD28 intracellular domain (UCB-1928zeta), both (UCB-1928BBzeta), or neither (UCB-19zeta). We found that UCB-19BBzeta and UCB-28BBzeta T cells exhibited more cytotoxicity to CD19(+) leukemia and lymphoma cell lines than UCB-19zeta and UCB-1928zeta, although differences in secretion of interleukin-2 and interferon-gamma by these T cells were not evident. In vivo adoptive transfer of these T cells into intraperitoneal tumor-bearing mice demonstrated that UCB-19BBzeta and UCB-1928BBzeta T cells mounted the most potent antitumor response. The mice adoptively transferred with UCB-1928BBzeta cells survived longer than the mice with UCB-19BBzeta. Moreover, UCB-1928BBzeta T cells mounted a more robust antitumor response than UCB-19BBzeta in a systemic tumor model. Our data suggest a synergistic role of 4-1BB and CD28 costimulation in engineering antileukemia UCB effector cells and implicate a design for redirected UCB T-cell therapy for refractory leukemia.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance.

Tumor drug resistance significantly limits the success of chemotherapy in the clinic. Tumor cells utilize multiple mechanisms to prevent the accumulation of anticancer drugs at their intracellular site of action. In this study, we investigated the anticancer efficacy of doxorubicin in combination with photodynamic therapy using methylene blue in a drug-resistant mouse tumor model. Surfactant-polymer hybrid nanoparticles formulated using an anionic surfactant, Aerosol-OT (AOT), and a naturally occurring polysaccharide polymer, sodium alginate, were used for synchronized delivery of the two drugs. Balb/c mice bearing syngeneic JC tumors (mammary adenocarcinoma) were used as a drug-resistant tumor model. Nanoparticle-mediated combination therapy significantly inhibited tumor growth and improved animal survival. Nanoparticle-mediated combination treatment resulted in enhanced tumor accumulation of both doxorubicin and methylene blue, significant inhibition of tumor cell proliferation, and increased induction of apoptosis. These data suggest that nanoparticle-mediated combination chemotherapy and photodynamic therapy using doxorubicin and methylene blue has significant therapeutic potential against drug-resistant tumors.

Inhibition of vinyl carbamate-induced pulmonary adenocarcinoma by indole-3-carbinol and myo-inositol in A/J mice.

In previous studies, we reported that indole-3-carbinol (I3C) and myo-inositol (MI) inhibit lung adenoma induced by tobacco smoke carcinogens in A/J mice. In this paper, we extended our work and examined the effects of I3C (70 or 30 micromol/g diet) and MI (56 micromol/g diet) against vinyl carbamate (VC)-induced lung adenocarcinoma by administering the agents from 1 week after the second of two injections of VC until termination of the study at week 18. The higher dose of I3C decreased multiplicities of tumors on the surface of the lung (26%, P = 0.0005), carcinoma incidence (38%), multiplicity (67%, P < 0.0001) and size (complete abolition of carcinoma with an area of >1.0 cm(2)) as well as adenoma with cellular pleomorphism (46%, P < 0.0001). The lower dose of I3C was less effective. MI decreased multiplicities of pulmonary surface tumors (20%, P = 0.0005), adenoma with cellular pleomorphism (40%, P < 0.0001) and lung adenoma (52%, P < 0.0001) and the proportion of the biggest carcinoma (carcinoma with an area of >1.0 cm(2), P < 0.05). Immunoblot analyses of lung tissues for potential target identification showed that I3C (70 micromol/g diet) inhibits IkappaBalpha degradation, nuclear factor-kappaB activation, expression of cyclooxygenase-2, phospho-Akt and fatty acid synthase (FAS) and activates caspase-3 and poly ADP ribose polymerase cleavage. The effect of MI was limited to inhibition of phospho-Akt and FAS expression. Our data show that I3C and MI inhibit lung carcinoma and provide a basis for future evaluation of these compounds in clinical trials as chemopreventive agents for current and former smokers.

The use of nanoparticle-mediated targeted gene silencing and drug delivery to overcome tumor drug resistance.

Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) enables cancer cells to develop resistance to multiple anticancer drugs. Functional inhibitors of P-gp have shown promising efficacy in early clinical trials, but their long-term safety is yet to be established. A novel approach to overcome drug resistance is to use siRNA-mediated RNA interference to silence the expression of the efflux transporter. Because P-gp plays an important role in the physiological regulation of endogenous and xenobiotic compounds in the body, it is important to deliver P-gp targeted siRNA and anticancer drug specifically to tumor cells. Further, for optimal synergy, both the drug and siRNA may need to be temporally colocalized in the tumor cells. In the current study, we investigated the effectiveness of simultaneous and targeted delivery of anticancer drug, paclitaxel, along with P-gp targeted siRNA, using poly(D,L-lactide-co-glycolide) nanoparticles to overcome tumor drug resistance. Nanoparticles were surface functionalized with biotin for active tumor targeting. Dual agent nanoparticles encapsulating the combination of paclitaxel and P-gp targeted siRNA showed significantly higher cytotoxicity in vitro than nanoparticles loaded with paclitaxel alone. Enhanced therapeutic efficacy of dual agent nanoparticles could be correlated with effective silencing of the MDR1 gene that encodes for P-gp and with increased accumulation of paclitaxel in drug-resistant tumor cells. In vivo studies in a mouse model of drug-resistant tumor demonstrated significantly greater inhibition of tumor growth following treatment with biotin-functionalized nanoparticles encapsulating both paclitaxel and P-gp targeted siRNA at a paclitaxel dose that was ineffective in the absence of gene silencing. These results suggest that that the combination of P-gp gene silencing and cytotoxic drug delivery using targeted nanoparticles can overcome tumor drug resistance.

Cytosine methylation effects on the repair of O6-methylguanines within CG dinucleotides.

O(6)-alkyldeoxyguanine adducts induced by tobacco-specific nitrosamines are repaired by O(6)-alkylguanine DNA alkyltransferase (AGT), which transfers the O(6)-alkyl group from the damaged base to a cysteine residue within the protein. In the present study, a mass spectrometry-based approach was used to analyze the effects of cytosine methylation on the kinetics of AGT repair of O(6)-methyldeoxyguanosine (O(6)-Me-dG) adducts placed within frequently mutated 5'-CG-3' dinucleotides of the p53 tumor suppressor gene. O(6)-Me-dG-containing DNA duplexes were incubated with human recombinant AGT protein, followed by rapid quenching, acid hydrolysis, and isotope dilution high pressure liquid chromatography-electrospray ionization tandem mass spectrometry analysis of unrepaired O(6)-methylguanine. Second-order rate constants were calculated in the absence or presence of the C-5 methyl group at neighboring cytosine residues. We found that the kinetics of AGT-mediated repair of O(6)-Me-dG were affected by neighboring 5-methylcytosine ((Me)C) in a sequence-dependent manner. AGT repair of O(6)-Me-dG adducts placed within 5'-CG-3' dinucleotides of p53 codons 245 and 248 was hindered when (Me)C was present in both DNA strands. In contrast, cytosine methylation within p53 codon 158 slightly increased the rate of O(6)-Me-dG repair by AGT. The effects of (Me)C located immediately 5' and in the base paired position to O(6)-Me-dG were not additive as revealed by experiments with hypomethylated sequences. Furthermore, differences in dealkylation rates did not correlate with AGT protein affinity for cytosine-methylated and unmethylated DNA duplexes or with the rates of AGT-mediated nucleotide flipping, suggesting that (Me)C influences other kinetic steps involved in repair, e.g. the rate of alkyl transfer from DNA to AGT.

Stable gene transfer and expression in cord blood-derived CD34+ hematopoietic stem and progenitor cells by a hyperactive Sleeping Beauty transposon system.

Here we report stable gene transfer in cord blood-derived CD34(+) hematopoietic stem cells using a hyperactive nonviral Sleeping Beauty (SB) transposase (SB100X). In colony-forming assays, SB100X mediated the highest efficiency (24%) of stable Discosoma sp red fluorescent protein (DsRed) reporter gene transfer in committed hematopoietic progenitors compared with both the early-generation hyperactive SB11 transposase and the piggyBac transposon system (1.23% and 3.8%, respectively). In vitro differentiation assays further demonstrated that SB100X-transfected CD34(+) cells can develop into DsRed(+) CD4(+)CD8(+) T (3.17%-21.84%; median, 7.97%), CD19(+) B (3.83%-18.66%; median, 7.84%), CD56(+)CD3(-) NK (3.53%-79.98%; median, 7.88%), and CD33(+) myeloid (7.59%-15.63%; median, 9.48%) cells. SB100X-transfected CD34(+) cells achieved approximately 46% engraftment in NOD-scid IL2gammac(null) (NOG) mice. Twelve weeks after transplantation, 0.57% to 28.96% (median, 2.79%) and 0.49% to 34.50% (median, 5.59%) of total human CD45(+) cells in the bone marrow and spleen expressed DsRed, including CD19(+) B, CD14(+) monocytoid, and CD33(+) myeloid cell lineages. Integration site analysis revealed SB transposon sequences in the human chromosomes of in vitro differentiated T, B, NK, and myeloid cells, as well as in human CD45(+) cells isolated from bone marrow and spleen of transplanted NOG mice. Our results support the continuing development of SB-based gene transfer into human hematopoietic stem cells as a modality for gene therapy.

Nanoparticle-mediated simultaneous and targeted delivery of paclitaxel and tariquidar overcomes tumor drug resistance.

Drug resistance is a major obstacle to the success of cancer chemotherapy. Overexpression of the drug-efflux transporter P-glycoprotein (P-gp) is a key factor contributing to tumor drug resistance. Third generation P-gp inhibitors like tariquidar have shown promising efficacy in early clinical trials. However, for maximum efficacy, it is important to limit the exposure of normal cells and tissues to the efflux inhibitor and the anticancer drug, and temporally colocalize the drug-inhibitor combination in the tumor cells. In this study, we investigated simultaneous and targeted delivery of anticancer drug, paclitaxel, with P-gp modulator, tariquidar, using poly(d,l-lactide-co-glycolide) nanoparticles to overcome tumor drug resistance. Nanoparticles were surface functionalized with biotin for active tumor targeting. Dual agent nanoparticles encapsulating the combination of paclitaxel and tariquidar showed significantly higher cytotoxicity in vitro than nanoparticles loaded with paclitaxel alone. Enhanced therapeutic efficacy of dual agent nanoparticles could be correlated with increased accumulation of paclitaxel in drug-resistant tumor cells. In vivo studies in a mouse model of drug-resistant tumor demonstrated significantly greater inhibition of tumor growth following treatment with biotin-functionalized nanoparticles encapsulating both paclitaxel and tariquidar at a paclitaxel dose that was ineffective in the absence of tariquidar. Taken together, these results suggest that the use of targeted, dual agent nanoparticles delivering a combination of P-gp modulator and anticancer drug is a very promising approach to overcome tumor drug resistance.

Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery.

Targeted drug delivery using nanocarriers is achieved by functionalizing the carrier surface with a tissue-recognition ligand. Current surface modification methods require tedious and inefficient synthesis and purification steps, and are not easily amenable to incorporating multiple functionalities on a single surface. In this report, we describe a versatile, single-step surface functionalizing technique for polymeric nanoparticles. The technique utilizes the fact that when a diblock copolymer like polylactide-polyethylene glycol (PLA-PEG) is introduced in the oil/water emulsion used in polymeric nanoparticle formulation, the PLA block partitions into the polymer containing organic phase and PEG block partitions into the aqueous phase. Removal of the organic solvent results in the formation of nanoparticles with PEG on the surface. When a PLA-PEG-ligand conjugate is used instead of PLA-PEG copolymer, this technique permits a 'one-pot' fabrication of ligand-functionalized nanoparticles. In the current study, the IAASF approach facilitated the simultaneous incorporation of biotin and folic acid, known tumor-targeting ligands, on drug-loaded nanoparticles in a single step. Incorporation of the ligands on nanoparticles was confirmed by using NMR, surface plasmon resonance, transmission electron microscopy and tumor cell uptake studies. Simultaneous functionalization with both ligands significantly enhanced nanoparticle accumulation in tumors in vivo, and resulted in greatly improved efficacy of paclitaxel-loaded nanoparticles in a mouse xenograft tumor model. This new surface functionalization approach will enable the development of targeting strategies based on the use of multiple ligands on a single surface to target a tissue of interest.