Salivary Excretion of Renal-Clearable Silver Nanoparticles.

Salivary elimination is an important pathway for the body to excrete small molecules with digestive enzymes. However, very few engineered nanoparticles can be excreted through salivary glands, which often host bacteria or viruses during infection and involve in disease transmission. Herein, we report that renal clearable glutathione coated AgNPs (GS-AgNPs) can selectively accumulate in the submandibular salivary gland, followed by being excreted in its excretory duct. By conducting head-to-head comparison on in vivo transport and interactions of both GS-AgNPs and glutathione coated gold nanoparticles (GS-AuNPs) with the same sizes, we found that low-density GS-AgNPs showed much higher vascular permeability than GS-AuNPs and can rapidly penetrate into submandibular salivary glands, be efficiently taken up by striated and excretory duct cells, and eventually secreted into saliva.

Photoacoustic Imaging of Nanoparticle Transport in the Kidneys at High Temporal Resolution.

Noninvasive monitoring of kidney elimination of engineered nanoparticles at high temporal and spatial resolution will not only significantly advance our fundamental understandings of nephrology on the nanoscale, but also aid in the early detection of kidney disease, which affects more than 10 % of the worldwide population. Taking advantage of strong NIR absorption of the well-defined Au25 (SG)18 nanocluster, photoacoustic (PA) imaging was used to visualize its transport in situ through the aorta to the renal parenchyma and its subsequent filtration into the renal pelvis at a temporal resolution down to 1 s. High temporal and spatial resolution imaging of Au25 (SG)18 kidney elimination allowed the accurate quantification of the glomerular filtration rate (GFR) of individual kidneys in normal and pathological conditions, broadening the biomedical applications of engineered nanoparticles in preclinical kidney research.

Antibacterial Activity of Silver Nanoparticles: Structural Effects.

The increase of antibiotic resistance in bacteria has become a major concern for successful diagnosis and treatment of infectious diseases. Over the past few decades, significant progress has been achieved on the development of nanotechnology-based medicines for combating multidrug resistance in microorganisms. Among this, silver nanoparticles (AgNPs) hold great promise in addressing this challenge due to their broad-spectrum and robust antimicrobial properties. This review illustrates the antibacterial mechanisms of silver nanoparticles and further elucidates how different structural factors including surface chemistry, size, and shape, impact their antibacterial activities, which are expected to promote the future development of more potent silver nanoparticle-based antibacterial agents.

Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles.

A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs. The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern. However, it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability. Glioblastoma multiforme, the most malignant orthotopic brain tumor, presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment. Herein, we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance. Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency (2.3× relative to surrounding non-tumor normal brain tissues) and greater specificity (3.0×) than did the larger AuNPs. Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation. The total accumulation of the 3-nm AuNPs in major organs was significantly less (8.4×) than that of the 18-nm AuNPs. Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium. Taken together, our results suggest that the 3-nm AuNPs, characterized by enhanced permeability and retention, are able to target brain tumors and undergo renal clearance.

Tailoring Renal Clearance and Tumor Targeting of Ultrasmall Metal Nanoparticles with Particle Density.

Identifying key factors that govern the in vivo behavior of nanomaterials is critical to the clinical translation of nanomedicines. Overshadowed by size-, shape-, and surface-chemistry effects, the impact of the particle core density on clearance and tumor targeting of inorganic nanoparticles (NPs) remains largely unknown. By utilizing a class of ultrasmall metal NPs with the same size and surface chemistry but different densities, we found that the renal-clearance efficiency exponentially increased in the early elimination phase while passive tumor targeting linearly decreased with a decrease in particle density. Moreover, lower-density NPs are more easily distributed in the body and have shorter retention times in highly permeable organs than higher-density NPs. The density-dependent in vivo behavior of metal NPs likely results from their distinct margination in laminar blood flow, which opens up a new path for precise control of nanomedicines in vivo.

Toxic effect of palladium on embryonic development of zebrafish.

Since palladium (Pd) is now increasingly used in modern industry, it progressively accumulates in the environment, especially in aquatic ecosystem. The potential toxicity of Pd has therefore caused extensive concern worldwidely. In the present study, we investigated the toxic effect of Pd on zebrafish development. Acute Pd exposure significantly decreased both the survival rate (LC50: 292.6 µg/L, viz. 2.75 µM) and hatching rate (IC50: 181.5 µg/L, viz. 1.71 µM) of zebrafish during embryonic development. The most common developmental defect observed in Pd treated embryos is pericardiac edema, which occurs in a dose-dependent manner. Whole mount immunostaining and histological studies revealed that Pd exposure would produce the elongated, string-like heart. The heartbeat rate of zebrafish embryos was also decreased after Pd exposure. Consistently, mRNA expression levels of several cardiac-related genes were affected by Pd, suggesting a potential molecular mechanism of Pd-induced cardiac malformation of zebrafish embryo. Moreover, similar to other metals, Pd exposure resulted in the elevated expression of general metal-inducible genes. It was also found that the expression of several antioxidant enzymes was significantly down-regulated in the presence of Pd. Taken together, our study investigated the effects of Pd on zebrafish embryonic development and its potential molecular mechanisms, paving the way for the full understanding of Pd toxicity.

Core-shell Pd@Au nanoplates as theranostic agents for in-vivo photoacoustic imaging, CT imaging, and photothermal therapy.

Uniform plasmonic Pd@Au core-shell bimetallic nanoplates are synthesized by seeded growth strategy. Surface modified with SH-PEG makes it good biocompatibility, prolonged blood circulation, and relatively high tumor accumulation. Enhanced tumor contrast effects can be obtained for in vivo photoacoustic/CT imaging after intravenous injection of Pd@Au-PEG. Moreover, efficient photothermal tumor ablation is achieved, guided by the imaging techniques. This work promises further exploration of the superiority of 2D nanostructures for in vivo biomedical applications.

Simultaneous photodynamic and photothermal therapy using photosensitizer-functionalized Pd nanosheets by single continuous wave laser.

In this work, we prepared chlorin e6 (Ce6)-functionalized Pd nanosheets (Pd-PEI-Ce6) for the photodynamic and photothermal combined therapy that use a single laser. To fabricate the Pd-PEI-Ce6 nanocomposite, photosensitizer Ce6 were chemically conjugated to polyethylenimine (PEI) and the formed Ce6-PEI conjugates were then anchored onto Pd nanosheets by electrostatic and coordination interaction. The prepared Pd-PEI-Ce6 nanocomposite were about 4.5 nm in size, exhibited broad, and strong absorption from 450 to 800 nm, good singlet oxygen generation capacity and photothermal conversion efficiency, and excellent biocompability. Significantly greater cell killing was observed when HeLa cells incubated with Pd-PEI-Ce6 were irradiated with the 660 nm laser, attributable to both Pd nanosheets-mediated photothermal ablation and the photodynamic destruction effect of photosensitizer Ce6. The double phototherapy effect was also confirmed in vivo. It was found that the Pd-PEI-Ce6 treated tumor-bearing mice displayed the enhanced therapeutic efficiency compared to that of Pd-PEI, or Ce6-treated mice. Our work highlights the promise of using Pd nanosheets for potential multimode cancer therapies.

Sub-10-nm Pd nanosheets with renal clearance for efficient near-infrared photothermal cancer therapy.

Efficient renal clearance is of fundamentally important property of nanoparticles for their in vivo biomedical applications. In this work, we report the successful synthesis of ultra-small Pd nanosheets (SPNS) with an average diameter of 4.4 nm and their application in photothermal cancer therapy using a near infrared laser. The ultra-small Pd nanosheets have strong optical absorption in the NIR region and high photothermal conversion efficiency (52.0%) at 808 nm. After being surface-functionalized with reduced glutathione (GSH), the SPNS-GSH was administered to mice to investigate the biodistribution, photothermal efficacy and tumor ablation in vivo. The in vivo photothermal therapy studies clearly demonstrate that surface modification with GSH allows the nanosheets to exhibit prolonged blood circulation and thus high accumulation in tumors. Upon 808 nm NIR irradiation, the tumors can be completely ablated. More importantly, with the size below the renal filtration limit (<10 nm), the GSHylated Pd nanosheets can be nicely cleared from body through the renal excretion route and into urine. Together with the high efficacy of NIR photothermal therapy, the unique renal clearance properties make the ultra-small Pd nanosheets promising for practical use in photothermal cancer therapy.

Amphiphilic modification and asymmetric silica encapsulation of hydrophobic Au-Fe3O4 dumbbell nanoparticles.

A facile method is developed for amphiphilic surface modification and asymmetric silica encapsulation of hydrophobic Au-Fe3O4 dumbbell nanoparticles. The obtained asymmetric Janus nanocomposites display tunable wettability, enhanced catalysis and better cell internalization as compared to those with complete silica encapsulation.

Polypyrrole nanoparticles for high-performance in vivo near-infrared photothermal cancer therapy.

Polypyrrole nanoparticles (PPy NPs) exhibit strong absorption in the near infrared (NIR) region. With an excellent photothermal efficiency of ~45% at 808 nm, sub-100 nm PPy NPs are demonstrated to be a promising photothermal agent for in vivo cancer therapy using NIR irradiation.

Pd nanosheet-covered hollow mesoporous silica nanoparticles as a platform for the chemo-photothermal treatment of cancer cells.

A versatile system combining chemotherapy with photothermal therapy for cancer cells using Pd nanosheet-covered hollow mesoporous silica nanoparticles is reported. While the hollow mesoporous silica core can be used to load anticancer drugs (i.e., doxorubicin) for chemotherapy, the Pd nanosheets on the surface of particles can convert NIR light into heat for photothermal therapy. More importantly, the loading of Pd nanosheets on hollow mesoporous silica nanospheres can dramatically increase the amount of cellular internalization of the Pd nanosheets: almost 11 times higher than the unloaded Pd nanosheets. The as-prepared nanocomposites efficiently deliver both drugs and heat to cancer cells to improve the therapeutic efficiency with minimal side effects. Compared with chemotherapy or photothermal therapy alone, the combination of chemotherapy and phototherapy can significantly improve the therapeutic efficacy, exhibiting a synergistic effect.

Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery.

PURPOSE: The goal of the present study was to synthesize mucoadhesive polymer - thiolated chitosan (TCS) from chitosan (CS), then prepared CS/TCS-sodium alginate nanoparticles (CS/TCS-SA NPs), determined which was more potential for ocular drug delivery. METHODS: A new method for preparing TCS was developed, and the characteristics were determined using Fourier transform infrared spectroscopy and the degree of thiol immobilized was measured by Ellman's reagent. Human corneal epithelium (HCE) cells were incubated with different concentrations of TCS for 48 h to determine the cell viabilities. CS/TCS-SA NPs were prepared and optimized by a modified ionic gelation method. The particle sizes, zeta potentials, Scanning electron microscopy images, mucoadhesion, in vitro cell uptake and in vivo studies of the two types of NP were compared. RESULTS: The new method enabled a high degree of thiol substitution of TCS, up to 1,411.01±4.02 µmol/g. In vitro cytocompatibility results suggest that TCS is nontoxic. Compared to CS-SA NPs, TCS-SA NPs were more stable, with higher mucoadhesive properties and could deliver greater amounts of drugs into HCE cells in vitro and cornea in vivo. CONCLUSIONS: TCS-SA NPs have better delivery capability, suggesting they have good potential for ocular drug delivery applications.

Etching growth under surface confinement: an effective strategy to prepare mesocrystalline Pd nanocorolla.

An etching growth strategy was developed to prepare corolla-like Pd mesocrystals consisting of unidirectionally aligned, well-spaced, and connected ultrathin (1.8-nm-thick) Pd nanosheets. The combined use of CO and Fe(3+) is critical to the successful synthesis of the branched corolla-like Pd mesocrystals. While CO functions as the surface-confining agent to allow anisotropic growth of the 1.8-nm-thick Pd nanosheets as branches, Fe(3+) etches the Pd seeds at the early stage of the reaction to induce formation of the branched structure. Inheriting the unique properties of 1.8-nm-thick Pd nanosheets, the as-prepared Pd mesocrystals display well-defined surface plasmon resonance absorption in the near-infrared region, a high electrochemically active surface area, and a significant photothermal effect when irradiated with a near-infrared laser. Owing to the presence of internal voids and increased apparent thickness, the Pd mesocrystals also exhibit several features superior to those of single-domain Pd nanosheets, making them promising for electrocatalysis and cancer photothermal therapy applications.

Silica coating improves the efficacy of Pd nanosheets for photothermal therapy of cancer cells using near infrared laser.

Thickness does matter! The ultrathin nature of 1.8 nm-thick Pd nanosheets prevents them entering cells effectively. A 13-times enhancement in the cells' uptake of the Pd nanosheets has now been achieved by silica coating together with surface functionalization, therefore significantly improving their NIR photothermal cell-killing efficacy.

Freestanding palladium nanosheets with plasmonic and catalytic properties.

Ultrathin metal films can exhibit quantum size and surface effects that give rise to unique physical and chemical properties. Metal films containing just a few layers of atoms can be fabricated on substrates using deposition techniques, but the production of freestanding ultrathin structures remains a significant challenge. Here we report the facile synthesis of freestanding hexagonal palladium nanosheets that are less than 10 atomic layers thick, using carbon monoxide as a surface confining agent. The as-prepared nanosheets are blue in colour and exhibit a well-defined but tunable surface plasmon resonance peak in the near-infrared region. The combination of photothermal stability and biocompatibility makes palladium nanosheets promising candidates for photothermal therapy. The nanosheets also exhibit electrocatalytic activity for the oxidation of formic acid that is 2.5 times greater than that of commercial palladium black catalyst.

Controlled formation of concave tetrahedral/trigonal bipyramidal palladium nanocrystals.

Novel concave Pd nanocrystals with uniform diameter were successfully prepared in the presence of formaldehyde. While the outer surfaces of the as-prepared concave Pd nanocrystals are {111}, the faces concave toward the polyhedral center are high-surface-energy {110} faces. The degree of concavity and therefore the percentage of {110} of the nanocrystals are tunable by varying the amount of formaldehyde and the reaction temperature. Owing to the existence of active {110} facets, the electrocatalytic activity of the concave Pd nanocrystals displays dependency on their degree of concavity.