Short-Wave Infrared Emitting Nanocomposites for Fluorescence-Guided Surgery.

Fluorescence-guided surgery (FGS) is an emerging technique for tissue visualization during surgical procedures. Structures of interest are labeled with exogenous probes whose fluorescent emissions are acquired and viewed in real-time with optical imaging systems. This study investigated rare-earth-doped albumin-encapsulated nanocomposites (REANCs) as short-wave infrared emitting contrast agents for FGS. Experiments were conducted using an animal model of 4T1 breast cancer. The signal-to-background ratio (SBR) obtained with REANCs was compared to values obtained using indocyanine green (ICG), a near-infrared dye used in clinical practice. Prior to resection, the SBR for tumors following intratumoral administration of REANCs was significantly higher than for tumors injected with ICG. Following FGS, evaluation of fluorescence intensity levels in excised tumors and at the surgical bed demonstrated higher contrast between tissues at these sites with REANC contrast than ICG. REANCs also demonstrated excellent photostability over 2 hours of continuous illumination, as well as the ability to perform FGS under ambient lighting, establishing these nanocomposites as a promising contrast agent for FGS applications.

Synthesis of deep red emitting Cu-In-Zn-Se/ZnSe quantum dots for dual-modal fluorescence and photoacoustic imaging.

CuInSe2 quantum dots (QDs) are one of the most important Cd-free fluorescent probes; they usually exhibited low fluorescence intensity, suggesting that a considerable amount of absorbed photon energy was lost as heat. In this study we aimed to improve the fluorescence intensity of CuInSe2 QDs and investigate their photoacoustic (PA) signal resulting from the heat dissipation, which was previously rarely reported. Cu-In-Zn-Se/ZnSe QDs were synthesized by adopting two strategies of Zn doping and ZnSe shell growth. It was found that there was an upper limit for Zn concentration beyond which the fluorescence intensity began to decrease. In addition, a blue shift of the emission peak of Cu-In-Zn-Se/ZnSe QDs was observed at high concentrations of ZnSe precursor due to the diffusion of excessive Zn. To prepare the dual-modal fluorescence and PA imaging probe, poly(maleic anhydride-alt-1-octadecene) (PMAO) modified with polyethylene glycol (PEG) was coated on the QDs, which led to a slight reduction in fluorescence. Cellular labeling on HeLa cells was performed to demonstrate the utility of these probes for fluorescence imaging. We further studied the in vitro PA imaging capabilities of the Cu-In-Zn-Se/ZnSe/PMAO-g-PEG nanoparticles, which showed a distinct PA signal beyond 1.0 mg ml-1. The current work demonstrated that a moderate amount of Zn doping is necessary for enhancing fluorescence and there is a limit beyond which the fluorescence will be diminished. We also demonstrated the proof of concept that Cu-In-Zn-Se/ZnSe QDs are able to serve as a potential PA imaging contrast agent.

Shortwave infrared emitting multicolored nanoprobes for biomarker-specific cancer imaging in vivo.

BACKGROUND: The ability to detect tumor-specific biomarkers in real-time using optical imaging plays a critical role in preclinical studies aimed at evaluating drug safety and treatment response. In this study, we engineered an imaging platform capable of targeting different tumor biomarkers using a multi-colored library of nanoprobes. These probes contain rare-earth elements that emit light in the short-wave infrared (SWIR) wavelength region (900-1700 nm), which exhibits reduced absorption and scattering compared to visible and NIR, and are rendered biocompatible by encapsulation in human serum albumin. The spectrally distinct emissions of the holmium (Ho), erbium (Er), and thulium (Tm) cations that constitute the cores of these nanoprobes make them attractive candidates for optical molecular imaging of multiple disease biomarkers. METHODS: SWIR-emitting rare-earth-doped albumin nanocomposites (ReANCs) were synthesized using controlled coacervation, with visible light-emitting fluorophores additionally incorporated during the crosslinking phase for validation purposes. Specifically, HoANCs, ErANCs, and TmANCs were co-labeled with rhodamine-B, FITC, and Alexa Fluor 647 dyes respectively. These Rh-HoANCs, FITC-ErANCs, and 647-TmANCs were further conjugated with the targeting ligands daidzein, AMD3100, and folic acid respectively. Binding specificities of each nanoprobe to distinct cellular subsets were established by in vitro uptake studies. Quantitative whole-body SWIR imaging of subcutaneous tumor bearing mice was used to validate the in vivo targeting ability of these nanoprobes. RESULTS: Each of the three ligand-functionalized nanoprobes showed significantly higher uptake in the targeted cell line compared to untargeted probes. Increased accumulation of tumor-specific nanoprobes was also measured relative to untargeted probes in subcutaneous tumor models of breast (4175 and MCF-7) and ovarian cancer (SKOV3). Preferential accumulation of tumor-specific nanoprobes was also observed in tumors overexpressing targeted biomarkers in mice bearing molecularly-distinct bilateral subcutaneous tumors, as evidenced by significantly higher signal intensities on SWIR imaging. CONCLUSIONS: The results from this study show that tumors can be detected in vivo using a set of targeted multispectral SWIR-emitting nanoprobes. Significantly, these nanoprobes enabled imaging of biomarkers in mice bearing bilateral tumors with distinct molecular phenotypes. The findings from this study provide a foundation for optical molecular imaging of heterogeneous tumors and for studying the response of these complex lesions to targeted therapy.

Facile Synthesis of Monodisperse Nanostructured Silver Micro-Colloids via Controlled Agglomeration and Coalescence.

Silver nanostructures have expansive applications in catalysis, photonic and electronic devices. In this work, nanostructured silver micro-colloids (MCs) with uniform in size and shape (size distribution <5%) were synthesized via rapid reduction of silver nitrate by ascorbic acid with controlled agglomeration and coalescence. We further propose that the formation of silver MCs was controlled by the chemical reaction kinetics which is governed by the concentration of reduced silver, Agº formed in solution. Preliminary electrical measurements of the highly conductive silver MCs demonstrated their potential application as inks for printed electronics.

Large Area Directed Self-Assembly of Sub-10 nm Particles with Single Particle Positioning Resolution.

Directed self-assembly of nanoparticles (DSA-n) holds great potential for device miniaturization in providing patterning resolution and throughput that exceed existing lithographic capabilities. Although nanoparticles excel at assembling into regular close-packed arrays, actual devices on the other hand are often laid out in sparse and complex configurations. Hence, the deterministic positioning of single or few particles at specific positions with low defect density is imperative. Here, we report an approach of DSA-n that satisfies these requirements with less than 1% defect density over micrometer-scale areas and at technologically relevant sub-10 nm dimensions. This technique involves a simple and robust process where a solvent film containing sub-10 nm gold nanoparticles climbs against gravity to coat a prepatterned template. Particles are placed individually into nanoscale cavities, or between nanoposts arranged in varying degrees of geometric complexity. Brownian dynamics simulations suggest a mechanism in which the particles are pushed into the template by a nanomeniscus at the drying front. This process enables particle-based self-assembly to access the sub-10 nm dimension, and for device fabrication to benefit from the wealth of chemically synthesized nanoparticles with unique material properties.

CXCR-4 Targeted, Short Wave Infrared (SWIR) Emitting Nanoprobes for Enhanced Deep Tissue Imaging and Micrometastatic Cancer Lesion Detection.

Realizing the promise of precision medicine in cancer therapy depends on identifying and tracking cancerous growths to maximize treatment options and improve patient outcomes. This goal of early detection remains unfulfilled by current clinical imaging techniques that fail to detect lesions due to their small size and suborgan localization. With proper probes, optical imaging techniques can overcome this by identifying the molecular phenotype of tumors at both macroscopic and microscopic scales. In this study, the first use of nanophotonic short wave infrared technology is proposed to molecularly phenotype small lesions for more sensitive detection. Here, human serum albumin encapsulated rare-earth nanoparticles (ReANCs) with ligands for targeted lesion imaging are designed. AMD3100, an antagonist to CXCR4 (a classic marker of cancer metastasis) is adsorbed onto ReANCs to form functionalized ReANCs (fReANCs). fReANCs are able to preferentially accumulate in receptor positive lesions when injected intraperitoneally in a subcutaneous tumor model. fReANCs can also target subtissue microlesions at a maximum depth of 10.5 mm in a lung metastatic model of breast cancer. Internal lesions identified with fReANCs are 2.25 times smaller than those detected with ReANCs. Thus, an integrated nanoprobe detection platform is presented, which allows target-specific identification of subtissue cancerous lesions.

Directed Self-Assembly of sub-10 nm Particles: Role of Driving Forces and Template Geometry in Packing and Ordering.

By comparing the magnitude of forces, a directed self-assembly mechanism has been suggested previously in which immersion capillary is the only driving force responsible for packing and ordering of nanoparticles, which occur only after the meniscus recedes. However, this mechanism is insufficient to explain vacancies formed by directed self-assembly at low particle concentrations. Utilizing experiments, and Monte Carlo and Brownian dynamics simulations, we developed a theoretical model based on a new proposed mechanism. In our proposed mechanism, the competing driving forces controlling the packing and ordering of sub-10 nm particles are (1) the repulsive component of the pair potential and (2) the attractive capillary forces, both of which apply at the contact line. The repulsive force arises from the high particle concentration, and the attractive force is caused by the surface tension at the contact line. Our theoretical model also indicates that the major part of packing and ordering of nanoparticles occurs before the meniscus recedes. Furthermore, utilizing our model, we are able to predict the various self-assembly configurations of particles as their size increases. These results lay out the interplay between driving forces during directed self-assembly, motivating a better template design now that we know the importance and the dominating driving forces in each regime of particle size.

Template-induced structure transition in sub-10 nm self-assembling nanoparticles.

We report on the directed self-assembly of sub-10 nm gold nanoparticles confined within a template comprising channels of gradually varying widths. When the colloidal lattice parameter is mismatched with the channel width, the nanoparticles rearrange and break their natural close-packed ordering, transiting through a range of structural configurations according to the constraints imposed by the channel. While much work has been done in assembling ordered configurations, studies of the transition regime between ordered states have been limited to microparticles under applied compression. Here, with coordinated experiments and Monte Carlo simulations we show that particles transit through a more diverse set of self-assembled configurations than observed for compressed systems. The new insight from this work could lead to the control and design of complex self-assembled patterns other than periodic arrays of ordered particles.

Early Detection of Myeloid-Derived Suppressor Cells in the Lung Pre-Metastatic Niche by Shortwave Infrared Nanoprobes.

Metastatic breast cancer remains a significant source of mortality amongst breast cancer patients and is generally considered incurable in part due to the difficulty in detection of early micro-metastases. The pre-metastatic niche (PMN) is a tissue microenvironment that has undergone changes to support the colonization and growth of circulating tumor cells, a key component of which is the myeloid-derived suppressor cell (MDSC). Therefore, the MDSC has been identified as a potential biomarker for PMN formation, the detection of which would enable clinicians to proactively treat metastases. However, there is currently no technology capable of the in situ detection of MDSCs available in the clinic. Here, we propose the use of shortwave infrared-emitting nanoprobes for the tracking of MDSCs and identification of the PMN. Our rare-earth albumin nanocomposites (ReANCs) are engineered to bind the Gr-1 surface marker of murine MDSCs. When delivered intravenously in murine models of breast cancer with high rates of metastasis, the targeted ReANCs demonstrated an increase in localization to the lungs in comparison to control ReANCs. However, no difference was seen in the model with slower rates of metastasis. This highlights the potential utility of MDSC-targeted nanoprobes to assess PMN development and prognosticate disease progression.

Defect Engineering of Low-Coordinated Metal-Organic Frameworks (MOFs) for Improved CO2 Access and Capture.

While metal-organic frameworks (MOFs) are promising gas adsorbents, their tortuous microporous structures cause additional resistance for gas diffusion, thus hindering the accessibility of interior active sites. Here, we present a practical strategy to incorporate missing cluster defects into a representative low-coordinated MOFs structure, Mg-MOF-74, while maintaining the stability of a defect-rich structure. In this proposed method, graphene oxide (GO) is employed as modulator, and crystallization time is varied to promote defect formation by altering the nucleation and crystal growth processes. The best performing GO-modified Mg-MOF-74 sample (MOF@GO 40 h) achieved 18% and 15% improvement in surface area and total pore volume, respectively, over pristine Mg-MOF-74. The reduced diffusion resistance to gas flow translates to increased accessibility for gas molecules to active Mg adsorption sites inside the MOFs, leading to enhanced CO2 capture performance; the CO2 uptake quantity of MOF@GO 40 h arrives at 6.06 mmol/g at 0.1 bar and at 9.17 mmol/g at 1 bar and 25 °C, 19.29% and 16.37% higher, respectively, than that of the pristine Mg-MOF-74, with a CO2/N2 selectivity around 17.36% greater than that of pristine Mg-MOF-74. Our study demonstrates a facile approach for incorporating defects into MOFs systems with low coordination environments, thus expanding the library of defect-rich MOFs beyond the current highly coordinated MOF systems.

Lanthanide clusters with chalcogen encapsulated Ln: NIR emission from nanoscale NdSe(x).

Ln(SePh)(3) (Ln = Ce, Pr, Nd) reacts with elemental Se in the presence of Na ions to give (py)(16)Ln(17)NaSe(18)(SePh)(16), a spherical cluster with a 1 nm diameter. All three rare-earth metals form isostructural products. The molecular structure contains a central Ln ion surrounded by eight five-coordinate Se(2-) that are then surrounded by a group of 16 Ln that define the cluster surface, with additional µ(3) and µ(5) Se(2-), µ(3) and µ(4) SePh(-), and pyridine donors saturating the vacant coordination sites of the surface Ln, and a Na ion coordinating to selenolates, a selenido, and pyridine ligands. NIR emission studies of the Nd compound reveal that this material has a 35% quantum efficiency, with four transitions from the excited state (4)F(3/2) ion to (4)I(9/2), (4)I(11/2), (4)I(13/2), and (4)I(15/2) states clearly evident. The presence of Na(+) is key to the formation of these larger clusters, where reactions using identical concentrations of Nd(SePh)(3) and Se with either Li or K led only to the isolation of (py)(8)Nd(8)Se(6)(SePh)(12).

Highly NIR-emissive lanthanide polyselenides.

Ln(SePh)(3) (Ln = Ce, Pr, Nd), prepared by reduction of PhSeSePh with elemental Ln and Hg catalyst, reacts with excess elemental Se to give (py)(11)Ln(7)Se(21)HgSePh, an ellipsoidal polyselenide cluster. The molecular structure contains two square arrays of eight- or nine-coordinate Ln fused at one edge to form a V shape that is also capped on the concave side by a centrally located nine-coordinate (Se(3))pyLn(Se(3)) and on the convex side by a 2-fold disordered SeHgSePh. The central Ln coordinates to selenido, triselenido, and pyridine ligands, while all other Ln coordinate to selenido, diselenido, triselenido, and pyridine ligands. Thermal treatment of the Pr compound at 650 °C gave Pr(2)Se(3) and Pr(3)Se(4). NIR emission studies of the Nd compound show four transitions from the excited-state (4)F(3/2) ion to (4)I(9/2), (4)I(11/2), (4)I(13/2), and (4)I(15/2) states. The (4)F(3/2) ion to (4)I(11/2) transition (1075 nm emission) exhibited 43% quantum efficiency. This is the highest quantum efficiency reported for a 'molecular' Nd compound and leads a group of selenide-based clusters that has shown extraordinary quantum efficiency. In terms of efficiency and concentration, these compounds compare favorably with solid-state materials.

A solvothermal route to size- and phase-controlled highly luminescent NaYF4:Yb,Er up-conversion nanocrystals.

Size-controlled hexagonal- and cubic-phase NaYF4:Yb,Er nanocrystals with bright fluorescent emission were successfully synthesized via a solvothermal approach at a relatively low temperature (< 300 degrees C). A mixture of ethanol and ethylene glycol or pure ethylene glycol was used as a solvent, whereby changing the ethanol concentration. It is found that, besides reaction temperature and time, the reactant concentration is an important factor to control crystal phase. High reactant concentration, high reaction temperature, high concentration of ethanol and long reaction durations are favorable to the formation of brightly emitting hexagonal-phase nanocrystals. The effects of these reaction conditions on the size and the luminescent properties of the as-prepared nanocrystals are discussed. It is found that 30-120 nm hexagonal NaYF4:Yb,Er nanoparticles can be prepared using 0.04 M reactant concentration in 0-60% ethanol solution at 220 degrees C for 24 h.

Biodegradable rare earth fluorochloride nanocrystals for phototheranostics.

Rare earth (RE) doped inorganic nanocrystals have been demonstrated as efficient contrast agents for deep tissue shortwave-infrared (SWIR) imaging with high sensitivities leading to potential early detection of tumors. However, a potential concern is the unknown long-term toxicity and incompatibility of inorganic nanocrystals. In this work, biodegradable rare earth nanocrystals of Nd doped SrFCl coated with polydopamine (SrFCl:Nd@PDA) were designed. Instead of traditional fluoride hosts, the chlorinated SrF2 (i.e. SrFCl) with low phonon energy which significantly improved the brightness of SrFCl:Nd in the SWIR region was used as the host. After coating with a NIR-absorptive PDA layer, the SrFCl:Nd nanoparticles serve as not only a contrast agent for photoacoustic imaging, but also a potential photothermal agent for cancer therapy. Moreover, these SrFCl:Nd@PDA nanoparticles can be rapidly and completely degraded in phosphate buffer solution within 1 h, which effectively addresses the concerns of the deleterious effects arising from potential long term accumulation. The increased accumulation and retention at tumor sites, and complete in vivo clearance ∼6 h after injection make these SrFCl:Nd@PDA nanoparticles a promising degradable phototheranostic agent.

Shortwave Infrared-Emitting Theranostics for Breast Cancer Therapy Response Monitoring.

Therapeutic drug monitoring (TDM) in cancer, while imperative, has been challenging due to inter-patient variability in drug pharmacokinetics. Additionally, most pharmacokinetic monitoring is done by assessments of the drugs in plasma, which is not an accurate gauge for drug concentrations in target tumor tissue. There exists a critical need for therapy monitoring tools that can provide real-time feedback on drug efficacy at target site to enable alteration in treatment regimens early during cancer therapy. Here, we report on theranostic optical imaging probes based on shortwave infrared (SWIR)-emitting rare earth-doped nanoparticles encapsulated with human serum albumin (abbreviated as ReANCs) that have demonstrated superior surveillance capability for detecting micro-lesions at depths of 1 cm in a mouse model of breast cancer metastasis. Most notably, ReANCs previously deployed for detection of multi-organ metastases resolved bone lesions earlier than contrast-enhanced magnetic resonance imaging (MRI). We engineered tumor-targeted ReANCs carrying a therapeutic payload as a potential theranostic for evaluating drug efficacy at the tumor site. In vitro results demonstrated efficacy of ReANCs carrying doxorubicin (Dox), providing sustained release of Dox while maintaining cytotoxic effects comparable to free Dox. Significantly, in a murine model of breast cancer lung metastasis, we demonstrated the ability for therapy monitoring based on measurements of SWIR fluorescence from tumor-targeted ReANCs. These findings correlated with a reduction in lung metastatic burden as quantified via MRI-based volumetric analysis over the course of four weeks. Future studies will address the potential of this novel class of theranostics as a preclinical pharmacological screening tool.

Near infrared-emitting Er- and Yb-Er- doped CeF3 nanoparticles with no visible upconversion.

In this work, a host which interacts and enhanced energy transfer to the luminescent center such that it facilitates the infrared emission while avoiding undesired emissions was found. An intense emission at approximately 1530 nm with no other visible emissions was observed in Er- and Yb-Er- doped CeF3 nanoparticles upon excitation at approximately 975 nm. The average measured luminescence lifetimes of the approximately 1530 nm emission for heat-treated CeF3:Er and CeF3:Yb,Er nanoparticles was approximately 4.5-6.5 ms, with internal quantum efficiencies up to approximately 52-75%. These nanoparticles offer a vast range of potential applications, which include optical amplifiers, waveguides, laser materials and infrared imaging probes.

Interfacial properties and in vitro cytotoxic effects of surface-modified near infrared absorbing Au-Au(2)S nanoparticles.

Near infrared (NIR) absorbing Au-Au(2)S nanoparticles were modified with surfactants of different hydrocarbon chain lengths to allow loading of anticancer drug, cisplatin. The interfacial interactions and surfactant chain length effects on drug loading, optical properties and cytotoxicity were discussed in this work. Short-chain surfactants were oriented closer to the surface normal and were adsorbed at higher densities. Surface modification also changed the optical properties of the particles. Notably, particles modified with short-chain surfactants exhibited a red shift, whereas particles modified with long-chain surfactants showed a blue shift. The in vitro cytotoxicity of drug-loaded surface-modified particles was dependent on the surfactants' chain length. Significant cytotoxicity was observed for 1 mg/ml of drug-loaded particles using surfactants with the shortest chain length. After NIR triggered drug release, the released Pt compounds were observed to be cytotoxic, while remaining nanoparticles did not exhibit any cytotoxicity. Also, the released Pt compounds upon NIR irradiation of drug-loaded particles were observed to be more toxic and had a different molecular structure from cisplatin.

High-Performance and Flexible Shortwave Infrared Photodetectors Using Composites of Rare Earth-Doped Nanoparticles.

The growing demand of infrared sensors for emerging applications such as autonomous vehicles and remote control and sensing systems has driven the development of flexible, low-power, and sensitive infrared detectors for seamless product integration. Although semiconducting polymer (SCP)-based photodetectors are promising solutions, challenges in synthesis chemistry and high thermal dark currents associated with narrowing of band gaps have limited their progress. To address these challenges, we have designed a new class of composites comprising SCPs with moderate band gap and rare earth doped-nanoparticles (RENPs) that enable photon-to-electron conversion beyond the SCP's response range. Using this RENP-SCP (RE-SCP) composite, we demonstrated detection at multiple wavelengths (808, 975, and 1532 nm) for planar-type photodetectors. Notably, the RE-SCP composite-based device detected an eye-safe, shortwave infrared (SWIR) source at 1532 nm with high SWIR responsivity of 0.02 A/W and an SWIR external quantum efficiency of 2%. The key attribute governing the excellent SWIR responsivity and sensitivity was the distinctive SWIR upconversion characteristic of RENPs that extended and improved the SCP's detection range and performance, respectively. Additionally, the absence of significant performance degradation of the SWIR photodetector for bending curvatures from 0-0.67 cm-1 highlights the promise of our RE-SCP composite-based flexible SWIR photodetectors.

Engineering the Infrared Luminescence and Photothermal Properties of Double-Shelled Rare-Earth-Doped Nanoparticles for Biomedical Applications.

The nascent field of theranostics, which couples targeted therapy with diagnostics, has catalyzed efforts toward improved nanoprobe designs that facilitate both localized treatment and diagnostic imaging. Rare-earth-doped nanoparticles (RENPs) have emerged as a leading candidate for theranostics because of their versatile synthesis and modification chemistries, photostability, and relative safety. Furthermore, their bright, tunable fluorescence using near-infrared (NIR) excitation enables multispectral imaging with high signal-to-background ratios. In this work, we have synthesized double-shelled RENPs with tunable properties for optimal fluorescent imaging, photoacoustic imaging, and photothermal therapy. The properties of the double-shelled RENPs were tailored by controlling the density of rare-earth ions (i.e., activator or sensitizer) by using either a functional amorphous organic or a crystalline outermost shell. This study systematically analyzes the effects of the functional organic or inorganic outermost shell on the imaging and photothermal conversion properties of our RENPs. Despite the weaker infrared absorption enhancement, the functional organic outermost shell impregnated with a low density of rare-earth ions led to minimal reduction of fluorescence emissions. In contrast, the higher density of rare-earth ions in the inorganic shell led to higher infrared absorption and consequently significant reduction in emissions arising from the undesired optical attenuation. Inorganic shell thickness was therefore modified to reduce the deleterious attenuation, leading to brighter emissions that also enabled the in vitro SWIR detection of ∼2500 cells/cluster. Using the enhanced infrared properties that arise from this functional inorganic layer, which could be engineered to respond to either NIR or SWIR, we demonstrated that (1) bright SWIR emissions allowed detection of small cell clusters; (2) strong PA signals allowed clear visualization of particle distribution within tumors; and (3) strong photothermal effects resulted in localized elevated temperatures. Collectively, these results highlight the utility of these double-shelled RENPs as theranostic agents that are compatible with both photoacoustic or fluorescent imaging platforms.

In vivo toxic studies and biodistribution of near infrared sensitive Au-Au(2)S nanoparticles as potential drug delivery carriers.

Near infrared (NIR) sensitive Au-Au(2)S nanoparticles are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of Au-Au(2)S nanoparticles with the biological milieu, their in vivo capabilities and limitations have not yet been explored. Au-Au(2)S nanoparticles and cisplatin-loaded Au-Au(2)S nanoparticles were successfully synthesized by the reduction of tetrachloroauric acid (HAuCl(4)) using sodium sulfide (Na(2)S), and cisplatin was loaded onto NIR sensitive Au-Au(2)S nanoparticles via an MUA (11-mercaptoundecanoic acid) layer. In this work, acute systemic toxicity in vivo, blood biochemistry assay, and tissue distribution in mice were carried out to further investigate the biocompatibility and biodistribution of these nanoparticles. The results from these studies demonstrated that both of nanoparticles (<200 microg/mL) might have a great advantage in biocompatibility and good biological safety.