Polyethylene Glycol Surface Research Articles

Comprehensive study of interaction between biocompatible PEG-InP/ZnS QDs and bovine serum albumin.

Polyethylene glycol (PEG) surface modified biocompatible InP/ZnS quantum dots (QDs) act as a potential alternative for conventional carcinogenic cadmium-based quantum dots for in vivo and in vitro studies. Comprehensively, we studied the interaction between a model protein bovine serum albumin (BSA) and PEGylated toxic free InP/ZnS QDs using various spectroscopic tools such as absorption, fluorescence quenching, time resolved and synchronous fluorescence spectroscopic measurements. These studies principally show that tryptophan (Trp) residues of BSA have preferable binding affinity towards PEG-InP/ZnS QDs surface and a blue shift in Trp fluorescence emission is a signature of conformational changes in its hydrophobic microenvironment. Photoluminescence (PL) intensity of Trp is quenched by ground state complex formation (static quenching) at room temperature. However, InP/ZnS@BSA conjugates become unstable with increasing temperature and PL intensity of Trp is quenched via dynamic quenching by PEG-InP/ZnS QDs. Experimentally determined thermodynamic parameters for these conjugates have shown spontaneity, entropy driven and exothermic nature of bio-conjugation. The calculated binding affinity (n ≅ 1, Hill coefficient) suggest that the affinity of InP/ZnS QDs for a BSA protein is not dependent on whether or not other BSA proteins are already bound to the QD surface. Energy transfer efficiency (E), Trp residue to InP/ZnS QDs distances and energy transfer rate (kT ) were all obtained from FÖrster resonance energy.

High capacity Li-ion battery anodes: Impact of crystallite size, surface chemistry and PEG-coating

Battery electrodes are complex mesoscale systems comprised of an active material, conductive agent, current collector, and polymeric binder. Previous work showed that introduction of poly [3-(potassium-4-butanoate) thiophene] (PPBT) as a binder component coupled with a polyethylene glycol (PEG) surface coating on magnetite (Fe3O4) nanoparticles enhanced electron and ion transport in the high capacity anode system. Here, the impact of Fe3O4 crystallite size (10 nm vs. 20 nm) and surface chemistry were explored to evaluate their effects on interfacial interactions within the composite PEG/PPBT based electrodes and resultant battery performance. The Fe3O4 synthesis methods inevitably lead to differences in surface chemistry. For instance, the Fe3O4 particles synthesized using ammonium hydroxide appeared more dispersed, and afforded improved rate capability performance. Notably, chemical interactions between the active nanoparticles and PPBT binder were only seen with particles synthesized using triethylamine. Capacity retention and cycling performance were unaffected. This study provides fundamental insights into the significant impact of active material synthesis on the design and fabrication of composite battery electrodes.

Small molecule delivery to solid tumors with chitosan-coated PLGA particles: A lesson learned from comparative imaging

For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs.

Dosimetric effects of polyethylene glycol surface coatings on gold nanoparticle radiosensitization

One of the main appeals of using gold nanoparticles (GNPs) as radiosensitizers is that their surface coatings can be altered to manipulate their pharmacokinetic properties. However, Monte Carlo studies of GNP dosimetry tend to neglect these coatings, potentially changing the dosimetric results. This study quantifies the dosimetric effects of including a polyethylene glycol (PEG) surface coating on GNPs over both nanoscopic and microscopic ranges. Two dosimetric scales were explored using PENELOPE Monte Carlo simulations. In microscopic simulations, 500–1000 GNPs, with and without coatings, were placed in cavities of side lengths 0.8–4 µm, and the reduction of dose deposited to surrounding medium within these volumes due to the coating was quantified. Including PEG surface coatings of up to 20 nm thickness resulted in reductions of up to 7.5%, 4.0%, and 2.0% for GNP diameters of 10, 20, and 50 nm, respectively. Nanoscopic simulations observed the dose falloff in the first 500 nm surrounding a single GNP both with and without surface coatings of various thicknesses. Over the first 500 nm surrounding a single GNP, the presence of a PEG surface coating reduced dose by 5–26%, 8–28%, 8–30%, and 8–34% for 2, 10, 20, and 50 nm diameter GNPs, respectively, for various energies and coating thicknesses. Reductions in dose enhancement due to the inclusion of a GNP surface coating are non-negligible and should be taken into consideration when investigating GNP dose enhancement. Further studies should be carried out to investigate the biological effects of these coatings.

Efficient Electrosteric Assembly of Nanoparticle Heterodimers and Linear Heteroassemblies.

Bottom-up approaches to the synthesis of nanostructures are of particular interest because they offer several advantages over the traditional top-down approaches. In this work, we present a new method to self-assemble nanoparticles into controlled heteroaggregates. The technique relies on carefully balancing attractive electrostatic forces with repulsive steric hindrance that is provided by surface-grafted polyethylene glycol (PEG). Two different-sized gold nanoparticles (GNPs) were used as a model system: 13 nm GNPs were functionalized with PEG-thiol and mercapto dodecanoic acid, while 7 nm GNPs were functionalized with PEG-thiol and (11- Mercaptoundecyl)trimethylammonium bromide. When mixed together, these oppositely charged particles self-assemble into stable colloidal structures (i.e., nanoclusters) whose structure depends strongly on the surface concentration of PEG. Smaller structures are obtained as the PEG surface concentration increases because steric hindrance dominates and prevents uncontrolled aggregation. In particular, under the right conditions, we were able to selectively synthesize heterodimers (which are effectively Janus particles) and linear heteroassemblies. This method is scalable, and it provides a step forward in bottom-up synthesis of nanomaterials.

Tumor Microenvironment-Responsive Multistaged Nanoplatform for Systemic RNAi and Cancer Therapy.

While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, the effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core. When the rationally designed, long circulating polymeric NPs accumulate in tumor tissues after intravenous administration, the targeted siRNA-TCPA complexes can be rapidly released via TME pH-mediated NP disassembly for subsequent specific targeting of tumor cells and cytosolic transport, thus achieving efficient gene silencing. In vivo results further demonstrate that the multistaged NP delivery of siRNA against bromodomain 4 (BRD4), a recently discovered target protein that regulates the development and progression of prostate cancer (PCa), can significantly inhibit PCa tumor growth.

Polarized, Cobblestone, Human Retinal Pigment Epithelial Cell Maturation on a Synthetic PEG Matrix.

Cell attachment is essential for the growth and polarization of retinal pigment epithelial (RPE) cells. Currently, surface coatings derived from biological proteins are used as the gold standard for cell culture. However, downstream processing and purification of these biological products can be cumbersome and expensive. In this study, we constructed a library of chemically modified nanofibers to mimic the Bruch's membrane of the retinal pigment epithelium. Using atmospheric-pressure plasma-induced graft polymerization with a high-throughput screening platform to modify the nanofibers, we identified three polyethylene glycol (PEG)-grafted nanofiber surfaces (PEG methyl ether methacrylate, n = 4, 8, and 45) from a library of 62 different surfaces as favorable for RPE cell attachment, proliferation, and maturation in vitro with cobblestone morphology. Compared with the biologically derived culture matrices such as vitronectin-based peptide Synthemax, our newly discovered synthetic PEG surfaces exhibit similar growth and polarization of retinal pigment epithelial (RPE) cells. However, they are chemically defined, are easy to synthesize on a large scale, are cost-effective, are stable with long-term storage capability, and provide a more physiologically accurate environment for RPE cell culture. To our knowledge, no one has reported that PEG derivatives directly support attachment and growth of RPE cells with cobblestone morphology. This study offers a unique PEG-modified 3D cell culture system that supports RPE proliferation, differentiation, and maturation with cobblestone morphology, providing a new avenue for RPE cell culture, disease modeling, and cell replacement therapy.

Modulation of the anti-inflammatory effects of phosphatidylserine-containing liposomes by PEGylation.

Inhibiting liposome uptake by macrophages using polyethylene glycol (PEG) surface modifications is a widely used approach for extending the half-life of liposomes circulating in the blood. However, the biological effects of PEGylated liposomes on macrophages have not yet been thoroughly investigated. The purpose of this study was to examine the effects of PEGylated phosphatidylserine-containing liposomes (PEG-PSLs) on the expression of two inflammation-associated cytokines, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), in the murine macrophage-like cell line RAW 264.7. Previous studies have demonstrated that PSLs inhibit TNF-α secretion and enhance TGF-β synthesis in macrophages by mimicking apoptotic cells. We found that PEGylation differentially affected the TNF-α and TGF-β levels. The PSL-mediated inhibitory effect on TNF-α secretion was enhanced by PEGylation, and PEG-PSLs decreased TGF-β levels compared with non-PEGylated PSLs. Fluorescence-activated cell sorting analysis demonstrated that 1% PEGylation disturbed the incorporation of PSLs into macrophages. The interference of uptake is thought to extend the binding interaction between PS to PS receptors for PSL-mediated inhibition of TNF-α expression. Together, these findings indicate that PEG-PSLs can prevent TNF-α secretion without increasing TGF-β levels in macrophages, and they support the potential clinical use of PEG-PSLs as anti-inflammatory agents with a relatively low potential to induce tissue fibrosis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1479-1486, 2017.

Preparation of core/shell nanostructure Fe3O4@PEG400-SO3H as heterogeneous and magnetically recyclable nanocatalyst for one-pot synthesis of substituted pyrroles by Paal-Knorr reaction at room temperature

An efficient procedure has been proposed for the loading of sulfonic acid groups on the surface of polyethylene glycol 400 (PEG400)-encapsulated Fe3O4 nanoparticles to synthesize a core–shell Fe3O4@PEG400-SO3H nano catalyst. Surface functionalization of magnetic particles in such a way is a refined method of bridging the gap amongst heterogeneous and homogeneous catalysis. The procured nano catalyst was classified through Fourier transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), wavelength-dispersive X-ray spectroscopy (WDX), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS), BET, and back titration. The nanoparticles have been utilized as a convenient catalyst for synthesizing a variety of N-substituted pyrroles via Paal-Knorr reactions of γ-diketones with amines, diamines or triamines at room temperature under solvent-free conditions. Notably, the newly produced catalyst was recoverable and recyclable (9 times) without any noticeable decrease in its activity.

Electron/Ion Transport Enhancer in High Capacity Li-Ion Battery Anodes

Magnetite (Fe3O4) was used as a model high capacity metal oxide active material to demonstrate advantages derived from consideration of both electron and ion transport in the design of composite battery electrodes. The conjugated polymer, poly[3-(potassium-4-butanoate) thiophene] (PPBT), was introduced as a binder component, while polyethylene glycol (PEG) was coated onto the surface of Fe3O4 nanoparticles. The introduction of PEG reduced aggregate size, enabled effective dispersion of the active materials and facilitated ionic conduction. As a binder for the composite electrode, PPBT underwent electrochemical doping which enabled the formation of effective electrical bridges between the carbon and Fe3O4 components, allowing for more efficient electron transport. Additionally, the PPBT carboxylic moieties effect a porous structure, and stable electrode performance. The methodical consideration of both enhanced electron and ion transport by introducing a carboxylated PPBT binder and PEG surface treatment l...

Facile Preparation of Multifunctional WS2 /WOx Nanodots for Chelator-Free 89 Zr-Labeling and In Vivo PET Imaging.

While position emission tomography (PET) is an important molecular imaging technique for both preclinical research and clinical disease diagnosis/prognosis, chelator-free radiolabeling has emerged as a promising alternative approach to label biomolecules or nanoprobes in a facile way. Herein, starting from bottom-up synthesized WS2 nanoflakes, this study fabricates a unique type of WS2 /WOx nanodots, which can function as inherent hard oxygen donor for stable radiolabeling with Zirconium-89 isotope (89 Zr). Upon simply mixing, 89 Zr can be anchored on the surface of polyethylene glycol (PEG) modified WS2 /WOx (WS2 /WOx -PEG) nanodots via a chelator-free method with surprisingly high labeling yield and great stability. A higher degree of oxidation in the WS2 /WOx -PEG sample (WS2 /WOx (0.4)) produces more electron pairs, which would be beneficial for chelator-free labeling of 89 Zr with higher yields, suggesting the importance of surface chemistry and particle composition to the efficiency of chelator-free radiolabeling. Such 89 Zr-WS2 /WOx (0.4)-PEG nanodots are found to be an excellent PET contrast agent for in vivo imaging of tumors upon intravenous administration, or mapping of draining lymph nodes after local injection.

Biocorona Bound Gold Nanoparticles Augment Their Hematocompatibility Irrespective of Size or Surface Charge.

Despite colloidal gold nanoparticles (AuNP) being proposed for a multitude of biomedical applications, there is a lack of understanding on how the protein corona (PC) formation over AuNP influences its interaction with blood components. Herein, 40 and 80 nm AuNP with branched polyethylenimine, lipoic acid, and polyethylene glycol surface coatings were exposed to human plasma, and time-dependent evolution of the PC was evaluated using differential centrifugation sedimentation. Further, the impact of PC-AuNP interaction with human blood components was studied by evaluating red blood cell (RBC) aggregation, hemolysis, platelet activation and aggregation, prothrombin time, activated partial thromboplastin time, complement activation and cytokine release. In contrast to bare AuNP, PC-coated AuNP exhibited enhanced compatibility with RBC, platelets, and lymphocytes. More importantly, PC-AuNP did not activate the platelet coagulation cascade or complement system or elicit an immune response up to a relatively higher dose of 100 μg/mL. This study suggests that, irrespective of the physicochemical properties, the adsorption of the PC over AuNP significantly influences its biological impact by alleviating adverse hematotoxicity of bare NP.

Targeted Superparamagnetic Iron Oxide Nanoparticles for In Vivo Magnetic Resonance Imaging of T-Cells in Rheumatoid Arthritis.

The purpose of the study is to develop a targeted nanoparticle platform for T cell labeling and tracking in vivo. Through carboxylation of the polyethylene glycol (PEG) surface of SPION, carboxylated-PEG-SPION (IOPC) was generated as a precursor for further conjugation with the targeting probe. The IOPC could readily cross-link with a variety of amide-containing molecules by exploiting the reaction between 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide and N-hydroxysuccinimide. The subsequent conjugation of monoclonal anti-CD3 antibody with IOPC made it possible to construct a magnetic resonance imaging (MRI) contrast agente (CA) that targets T cells, named IOPC-CD3. IOPC-CD3 was found to have high transverse relaxivity, good targeting selectivity, and good safety profile in vitro. The utility of this newly synthesized CA was explored in an in vivo rodent collagen-induced arthritis (CIA) model of rheumatoid arthritis. Serial MRI experiments revealed a selective decrease in the signal-to-noise ratio of the femoral growth plates of CIA rats infused with IOPC-CD3, with this finding being consistent with immunohistochemical results showing the accumulation of T cells and iron oxide nanoparticles in the corresponding region. Together with the abovementioned desirable features, these results indicate that IOPC-CD3 offers a promising prospect for a wide range of cellular and molecular MRI applications.

Label-free electrochemical impedance peptide-based biosensor for the detection of cardiac troponin I incorporating gold nanoparticles modified carbon electrode

A label-free electrochemical impedance spectroscopy (EIS) biosensor for highly sensitive detection of cardiac troponin I (TnI) as a model target was developed by employing gold nanoparticle (GNPs) modified glassy carbon electrode (GCE) as a base electrode. A special peptide (CFYSHSFHENWPS) was used as molecular recognition probe. GNPs were firstly electrochemically deposited onto the surface of GCE and polyethylene glycol was then used to block any remaining sites of the surface of GCE. The biosensor was fabricated by thiol self-assembling the peptide probe onto the surface of gold nanoparticles and finally blocking any remaining sites of the surface of GNPs using 6-mercapto-1-hexanol. A suitable equivalent electrical circuit consisting of parallel double Randles circuit with phase angle elements greatly fits the experiment electrochemical cell. Upon the binding of TnI, the charge transfer resistance (Rct) of the biosensor was logarithmically direct proportional to the concentration of TnI in the range from 15.5pg/mL to 1.55ng/mL with a detection limit of 3.4pg/mL. It was found that GNPs modified GCE as a platform for the immobilization of the peptide can greatly reduce the background EIS signal and enhance the EIS response to the target. This biosensor has been used for assay of real serum sample with satisfactory results. This work demonstrates that GNPs modified GCE for the immobilization of molecular recognition element is promising platform for the development of label-free electrochemical biosensors for the determination of special proteins.

Enhancing tumor penetration and targeting using size-minimized and zwitterionic nanomedicines

We report a strategy to significantly improve tumor penetration of nanomedicines by using size-minimized and zwitterionic nanocarriers. We synthesized a series of 21-arm star block copolymers with the hydrodynamic diameter of 10–40nm and conjugated doxorubicin to the copolymers through pH-sensitive acylhydrazone linkages. The zwitterionic poly(carboxybetaine) (PCB), nonionic polyethylene glycol (PEG) and phenylboronic acid-incorporated PCB were selected as the peripherial hydrophilic blocks of the copolymers, respectively. We demonstrated that the size-minimized multiarm copolymer with PCB surface showed stronger tumor permeability when compared to the copolymers with PEG surface or larger size. The drug-conjugated multiarm copolymer that has the longest blood circulation time did not achieve the highest tumor accumulation. The incorporation of phenylboronic acid group into the peripherial block of the drug-conjugated multiarm copolymer significantly enhanced their cytotoxicity, cellular uptake, tumor accumulation, tumor permeability and antitumor activity.

Narrow Absorption NIR Wavelength Organic Nanoparticles Enable Multiplexed Photoacoustic Imaging.

Photoacoustic (PA) imaging is an emerging hybrid optical-ultrasound based imaging technique that can be used to visualize optical absorbers in deep tissue. Free organic dyes can be used as PA contrast agents to concurrently provide additional physiological and molecular information during imaging, but their use in vivo is generally limited by rapid renal clearance for soluble dyes and by the difficulty of delivery for hydrophobic dyes. We here report the use of the block copolymer directed self-assembly process, Flash NanoPrecipitation (FNP), to form series of highly hydrophobic optical dyes into stable, biocompatible, and water-dispersible nanoparticles (NPs) with sizes from 38 to 88 nm and with polyethylene glycol (PEG) surface coatings suitable for in vivo use. The incorporation of dyes with absorption profiles within the infrared range, that is optimal for PA imaging, produces the PA activity of the particles. The hydrophobicity of the dyes allows their sequestration in the NP cores, so that they do not interfere with targeting, and high loadings of >75 wt % dye are achieved. The optical extinction coefficients (ε (mL mg(-1) cm(-1))) were essentially invariant to the loading of the dye in NP core. Co-encapsulation of dye with vitamin E or polystyrene demonstrates the ability to simultaneously image and deliver a second agent. The PEG chains on the NP surface were functionalized with folate to demonstrate folate-dependent targeting. The spectral separation of different dyes among different sets of particles enables multiplexed imaging, such as the simultaneous imaging of two sets of particles within the same animal. We provide the first demonstration of this capability with PA imaging, by simultaneously imaging nontargeted and folate-targeted nanoparticles within the same animal. These results highlight Flash NanoPrecipitation as a platform to develop photoacoustic tools with new diagnostic capabilities.

Multistage Delivery Technologies: Multifunctional, Interdisciplinary Approaches to Nanomedicine

Nanomedicine frequently employs single particles ranging from very simple1 to highly multifunctional.2 However, the diversity of barriers to effective transport can limit the global optimization of delivery for such systems. Multistage particles present an effective means to overcome such issues, allowing scientists to better segment the delivery mechanism into discrete steps by combining multiple formulations for sequential utility in vivo. A recent article in Nature Biotechnology highlights such a system,3 delivering nanoformulated doxorubicin (Dox) within larger disc-shaped, mesoporous silica particles (MSPs).

Silica–Polymer Hybrid with Self‐Assembled PEG Corona Excreted Rapidly via a Hepatobiliary Route

Nanotechnology‐based diagnostics and therapeutics usually suffer from long‐term retention of nanosized devices in the major organs, which may cause unwanted side effects. Herein, we describe the development of ultra‐small silica‐polymer hybrid dots (Sdots) through the self‐assembly between a polyethylene oxide‐poly(propylene oxide)‐polyethylene oxide (PEO‐PPO‐PEO) triblock copolymer and a silica precursor. Sdots feature a silica particle size of 4.2 nm and a hydrated size of 14 nm. The larger hydrated size is related to their polyethylene glycol (PEG) surface ligands, which evolve from the PEO blocks in the copolymer. The densely packed PEG corona can effectively shield the hybrid from reticuloendothelial uptake, which gives rise to rapid and thorough hepatobiliary clearance. In vivo experiments demonstrated that, upon intravenous injection, almost complete clearance of Sdots from mouse bodies could be realized through hepatobiliary excretion within only 5 days. Compared to renal clearable nanoparticles with short blood‐circulation times, the proposed Sdots have a prolonged blood‐circulation half‐life of 19 h, so that the Sdots could effectively accumulate at a subcutaneous transplanted tumor through enhanced penetration and retention. As the PPO core of the Sdots can be utilized to accommodate hydrophobic guest molecules, such as anticancer drugs, these Sdots can prospectively serve as fast‐clearable drug carriers for targeted cancer treatment.

Simple and Sensitive Molecularly Imprinted Polymer – Mn-Doped ZnS Quantum Dots Based Fluorescence Probe for Cocaine and Metabolites Determination in Urine

A new molecularly imprinted polymer (MIP)-based fluorescent artificial receptor has been prepared by anchoring a selective MIP for cocaine (COC) on the surface of polyethylene glycol (PEG) modified Mn-doped ZnS quantum dots (QDs). The prepared material combines the high selectivity attributed to MIPs and the sensitive fluorescent property of the Mn-doped ZnS QDs. Simple and low cost methods have therefore been optimized for assessing cocaine abuse in urine by monitoring the fluorescence quenching when the template (COC) and also metabolites from COC [benzoylecgonine (BZE) and ecgonine methyl ester (EME)] are present. Fluorescence quenching was not observed when performing experiments with other drugs of abuse (and their metabolites) or when using nonimprinted polymer (NIP)-coated QDs. Under optimized operating conditions (1.5 mL of 200 mg L(-1) MIP-coated QDs solution, pH 5.5, and 15 min before fluorescence scanning) two analytical methods were developed/validated. One of the procedures (direct method) consisted of urine sample 1:20 dilution before fluorescence measurements. The method has been found to be fast, precise, and accurate, but the standard addition technique for performing the analysis was required because of the existence of matrix effect. The second procedure performed a solid phase extraction (SPE) first, avoiding matrix effect and allowing external calibration. The limits of detection of the methods were 0.076 mg L(-1) (direct method) and 0.0042 mg L(-1) (SPE based method), which are lower than the cutoff values for confirmative conclusions regarding cocaine abuse.

Long circulating reduced graphene oxide-iron oxide nanoparticles for efficient tumor targeting and multimodality imaging.

Polyethylene glycol (PEG) surface modification is one of the most widely used approaches to improve the solubility of inorganic nanoparticles, prevent their aggregation and prolong their in vivo blood circulation half-life. Herein, we developed double-PEGylated biocompatible reduced graphene oxide nanosheets anchored with iron oxide nanoparticles (RGO-IONP-(1st)PEG-(2nd)PEG). The nanoconjugates exhibited a prolonged blood circulation half-life (∼27.7 h) and remarkable tumor accumulation (>11 %ID g(-1)) via an enhanced permeability and retention (EPR) effect. Due to the strong near-infrared absorbance and superparamagnetism of RGO-IONP-(1st)PEG-(2nd)PEG, multimodality imaging combining positron emission tomography (PET) imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging was successfully achieved. The promising results suggest the great potential of these nanoconjugates for multi-dimensional and more accurate tumor diagnosis and therapy in the future.