Controllable-Swelling Microneedle-Assisted Ultrasensitive Paper Sensing Platforms for Personal Health Monitoring.

Microneedle (MN) patches, which allow the extraction of skin interstitial fluid (ISF) without a pain sensation, are powerful tools for minimally invasive biofluid sampling. Herein, an MN-assisted paper-based sensing platform that enables rapid and painless biofluid analysis with ultrasensitive molecular recognition capacity is developed. First, a controllable-swelling MN patch is constructed through the engineering of a poly(ethylene glycol) diacrylate/methacrylated hyaluronic acid hydrogel; it combines rapid, sufficient extraction of ISF with excellent structural integrity. Notably, the analyte molecules in the needles can be recovered into a moist cellulose paper through spontaneous diffusion. More importantly, the paper can be functionalized with enzymatic colorimetric reagents or a plasmonic array, enabling a desired detection capacity-for example, the use of paper-based surface-enhanced Raman spectroscopy sensors leads to label-free, trace detection (sub-ppb level) of a diverse set of molecules (cefazolin, nicotine, paraquat, methylene blue). Finally, nicotine is selected as a model drug to evaluate the painless monitoring of three human volunteers. The changes in the nicotine levels can be tracked, with the levels varying significantly in response to the metabolism of drug in different volunteers. This as-designed minimally invasive sensing system should open up new opportunities for precision medicine, especially for personal healthcare monitoring.

Direct Thermal Growth of Gold Nanopearls on 3D Interweaved Hydrophobic Fibers as Ultrasensitive Portable SERS Substrates for Clinical Applications.

Surface-enhanced Raman spectroscopy (SERS)-based biosensors have attracted much attention for their label-free detection, ultrahigh sensitivity, and unique molecular fingerprinting. In this study, a wafer-scale, ultrasensitive, highly uniform, paper-based, portable SERS detection platform featuring abundant and dense gold nanopearls with narrow gap distances, are prepared and deposited directly onto ultralow-surface-energy fluorosilane-modified cellulose fibers through simple thermal evaporation by delicately manipulating the atom diffusion behavior. The as-designed paper-based SERS substrate exhibits an extremely high Raman enhancement factor (3.9 × 1011 ), detectability at sub-femtomolar concentrations (single-molecule level) and great signal reproductivity (relative standard deviation: 3.97%), even when operated with a portable 785-nm Raman spectrometer. This system is used for fingerprinting identification of 12 diverse analytes, including clinical medicines (cefazolin, chloramphenicol, levetiracetam, nicotine), pesticides (thiram, paraquat, carbaryl, chlorpyrifos), environmental carcinogens (benzo[a]pyrene, benzo[g,h,i]perylene), and illegal drugs (methamphetamine, mephedrone). The lowest detection concentrations reach the sub-ppb level, highlighted by a low of 16.2 ppq for nicotine. This system appears suitable for clinical applications in, for example, i) therapeutic drug monitoring for individualized medication adjustment and ii) ultra-early diagnosis for pesticide intoxication. Accordingly, such scalable, portable and ultrasensitive fibrous SERS substrates open up new opportunities for practical on-site detection in biofluid analysis, point-of-care diagnostics and precision medicine.

Aluminum Plasmonic Nanoclusters for Paper-Based Surface-Enhanced Raman Spectroscopy.

Although surface-enhanced Raman spectroscopy (SERS) can rapidly identify molecular fingerprints and has great potential for analysis, the need for delicate plasmonic substrates and complex laboratory instruments seriously limits its applicability for on-site detection. This paper describes the development of an inexpensive aluminum nanoparticle (AlNP)-decorated paper that functions as a facile SERS-based detection platform (Al-PSERS). Polydopamine-protected AlNPs were chemically synthesized and then simply drop-cast onto a hydrophobic cellulose paper, forming a monolayer AlNP cluster array. Because of the abundance of hot spots arising from the plasmonic clusters, the inherent quasi-three-dimensional structure of the cellulose fibers, and the concentration effect of the hydrophobic surface, the Al-PSERS provided significant enhancements to the signal of various analytes, measured using a portable 785 nm Raman spectrometer. Near-field optical simulations and experimental spectroscopic results revealed that the local electric fields and corresponding SERS signal intensities of the AlNP array exhibited clear particle-length and cluster-size dependencies. Therefore, the Al-PSERS could be optimized to provide high sensitivity (enhancement factor: 2 × 103) and excellent reproducibility (variation: 8.72%). Moreover, the optimal Al-PSERS was capable of detecting colorants and environmental pollutants; for example, the detection limits of allura red and benzo[a]pyrene reached as low as 3.5 and 0.15 ppm, respectively. Furthermore, the Al-PSERS could rapidly identify illegal (rhodamine B) and edible (allura red, erythrosine) colorants from a mixture of multiple colorants or from adulterated candies. Because it facilitates rapid detection, is of low cost, and has minimal technical requirements, Al-PSERS should be applicable to on-site detection in, for example, food inspection and environmental monitoring.

Wafer-scale nanocracks enable single-molecule detection and on-site analysis.

Large-area surface-enhanced Raman spectroscopy (SERS) sensing platforms displaying ultrahigh sensitivity and signal uniformity have potentially enormous sensing applicability, but they are still challenging to prepare in a scalable manner. In this study, silver nanopaste (AgNPA) was employed to prepare a wafer-scale, ultrasensitive SERS substrate. The self-generated, high-density Ag nanocracks (NCKs) with small gaps could be created on Si wafers via a spin-coating process, and provided extremely abundant hotspots for SERS analyses with ultrahigh sensitivity-down to the level of single molecules (enhancement factor: ca. 1010; detection limit: ca. 10-18 M)-and great signal reproducibility (variation: ca. 3.6%). Moreover, the Ag NCK arrays demonstrated broad applicability and practicability for on-site detection when combined with a portable 785 Raman spectrometer. This method allowed the highly sensitive detection of a diverse range of analytes (benzo[a]pyrene, di-2-ethylhexyl phthalate, aflatoxins B1, zearalenone, ractopamine, salbutamol, sildenafil, thiram, dimethoate, and methamidophos). In particular, pesticides are used extensively in agricultural production. Unfortunately, they can affect the environment and human health as a result of acute toxicity. Therefore, the simultaneous label-free detection of three different pesticides was demonstrated. Finally, the SERS substrates are fabricated through a simple, efficient, and scalable process that offers new opportunities for mass production.

Substrate-independent adsorption of nanoparticles as anti-biofilm coatings.

Healthcare-associated infections are common causes of morbidity and mortality. Advanced nanotechnology provides a means of overcoming this problem, but it remains challenging to develop universal coating strategies for decorating antimicrobial nanomaterials onto various clinical devices. In this paper, we propose a general silane-based method for immobilizing monolayer metal nanoparticle (NP) arrays onto any type of substrate surface-especially for a diverse range of clinical implantable devices. The surface silanization was achieved simply through the adsorption of N1-(3-trimethoxysilylpropyl)diethylenetriamine (TMS), regardless of the material (polymer, metal, oxide) or morphology (flat, curved, textured) of the substrate, with no need for pretreatment or expensive instrumentation. Monolayers of various nanostructures (Ag, Au, and hollow Au NPs) were then decorated rapidly onto the TMS-treated substrates, thereby further functionalizing their surfaces. In particular, immobilization of the Ag NPs resulted in excellent anti-biofilm efficacy against three clinically life-threatening pathogens: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Sustained release of Ag+ ions led to durable inhibition of bacterial attachment for up to 28 days. Studies with NIH3T3 fibroblasts revealed that the Ag NP arrays displayed no cytotoxicity toward mammalian cells. Overall, this universal coating process appears to be an innovative method for the surface-functionalization of diverse materials and devices employed in the fields of energy, sensing, and medicine-especially to prevent healthcare-associated infections arising from the use of clinical implantable devices in hospitals.

Reversal of pancreatic desmoplasia by a tumour stroma-targeted nitric oxide nanogel overcomes TRAIL resistance in pancreatic tumours.

OBJECTIVE: Stromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC. DESIGN: Nitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC. We applied an in vitro-in vivo combinatorial phage display technique to identify novel peptide ligands to target the desmoplastic stroma in both murine and human orthotopic PDAC. We then constructed a stroma-targeted nanogel modified with phage display-identified tumour stroma-targeting peptides to co-deliver NO and TRAIL to PDAC and examined the anticancer effect in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo. RESULTS: The delivery of NO to the PDAC tumour stroma resulted in reprogramming of activated pancreatic stellate cells, alleviation of tumour desmoplasia and downregulation of antiapoptotic BCL-2 protein expression, thereby facilitating tumour penetration by TRAIL and substantially enhancing the antitumour efficacy of TRAIL therapy. CONCLUSION: The co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumour microenvironment and suppresses tumour growth has the potential to be translated into a safe and promising treatment for PDAC.

Robust O2 Supplementation from a Trimetallic Nanozyme-Based Self-Sufficient Complementary System Synergistically Enhances the Starvation/Photothermal Therapy against Hypoxic Tumors.

Much effort has been focused on novel nanomedicine for cancer therapy. However, tumor hypoxia limits the efficacy of various cancer therapeutics. Herein, we constructed a self-sufficient hybrid enzyme-based silk fibroin hydrogel system, consisting of Pt-decorated hollow Ag-Au trimetallic nanocages (HGN@Pt) and glucose oxidase (GOx), to supply O2 continuously and consume glucose concurrently and, thereby, synergistically enhance the anti-cancer efficacy of a combined starvation and photothermal therapy operating in a hypoxic tumor microenvironment. Thanks to the cooperative effects of the active surface atoms (resulting from the island-like features of the Pt coating), the intrinsically hollow structure, and the strain effect induced by the trimetallic composition, HGN@Pt displayed efficient catalase-like activity. The enhancement in the generation of O2 through the decomposition of H2O2 mediated by the as-designed nanozyme was greater than 400% when compared with that of hollow Ag-Pt bimetallic nanospheres or tiny Pt nanoparticles. Moreover, in the presence of HGN@Pt, significant amounts of O2 could be generated within a few minutes, even in an acidic buffer solution (pH 5.8-6.5) containing a low concentration of H2O2 (100-500 µM). Because HGN@Pt exhibited a strong surface plasmon resonance peak in the near-infrared wavelength range, it could be used as a photothermal agent for hyperthermia therapy. Furthermore, GOx was released gradually from the SF hydrogel into the tumor microenvironment to mediate the depletion of glucose, leading to glucose starvation-induced cancer cell death. Finally, the O2 supplied by HGN@Pt overcame the hypoxia of the microenvironment and, thereby, promoted the starvation therapeutic effect of the GOx-mediated glucose consumption. Meanwhile, the GOx-produced H2O2 from the oxidation of glucose could be used to regenerate O2 and, thereby, construct a complementary circulatory system. Accordingly, this study presents a self-sufficient hybrid enzyme-based system that synergistically alleviates tumor hypoxia and induces an anti-cancer effect when combined with irradiation of light from a near-infrared laser.

Dual-functional antibiofilm polymer composite for biodegradable medical devices.

Urinary tract infections (UTI) represent one of the most common problem within the urological disorders, and it is mainly caused by biofilm formation which leads to bacterial infection. Anti-adhesion and antibacterial agents are two primary mechanisms to prevent biofilm formation; however, current strategies are insufficiently effective. In this study, we developed an effective antibiofilm biodegradable polymer with high biocompatibility. Here we embedded silver nanoparticles (AgNPs) in poly(glycerol sebacate) acrylate (PGSA) followed by superhydrophilic modification on the polymer surfaces. The modified surfaces were characterized using SEM, AFM and contact angle measurements. This anti-adhesive surface prevented the adhesion of E. coli and limited the biofilm coverage percentage to less than 3% in 24 h. In the in vitro degradation, the long-term antibiofilm performance was evaluated in Nowatzki-Stoodley artificial urine (NSAU). The surface modified AgNPs embedded PGSA (sPGSA-AgNPs) was able to effectively inhibit the formation of biofilm by reducing the biofilm coverage to less than 0.01%, and it also showed low cytotoxicity with human bladder carcinoma cell. With the effective antibiofilm, biocompatibility and biodegradability, it is possible to be applied in urological devices to ameliorate the situation of UTIs.

Diverse Substrate-Mediated Local Electric Field Enhancement of Metal Nanoparticles for Nanogap-Enhanced Raman Scattering.

The localized surface plasmon resonance of plasmonic nanoparticles (NPs) can be coupled with a noble metal substrate (S) to induce a localized augmented electric field (E-field) concentrated at the NP-S gap. Herein, we analyzed the fundamental near-field properties of metal NPs on diverse substrates numerically (using the 3D finite-difference time-domain method) and experimentally [using surface-enhanced Raman scattering (SERS)]. We systematically examined the effects of plasmonic NPs on noble metals (Ag and Au), non-noble metals (Al, Ti, Cu, Fe, and Ni), semiconductors (Si and Ge), and dielectrics (TiO2, ZnO, and SiO2) as substrates. For the AgNPs, the Al (11,664 times) and Si (3969 times) substrates produced considerable E-field enhancements, with Al in particular generating a tremendous E-field enhancement comparable in intensity to that induced by a Ag (28,224 times) substrate. Notably, we found that a superior metallic character of the substrate gave rise to easier induction of image charges within the metal substrate, resulting in a greater E-field at the NP-S gap; on the other hand, the larger the permittivity of the nonmetal substrate, the greater the ability of the substrate to store an image charge distribution, resulting in stronger coupling to the charges of localized surface plasmon resonance oscillation on the metal NP. Furthermore, we measured the SERS spectra of rhodamine 6G (a commonly used Raman spectral probe), histamine (a biogenic amine used as a food freshness indicator), creatinine (a kidney health indicator), and tert-butylbenzene [an extreme ultraviolet (EUV) lithography contaminant] on AgNP-immobilized Al and Si substrates to demonstrate the wide range of potential applications. Finally, the NP-S gap hotspots appear to be widely applicable as an ultrasensitive SERS platform (∼single-molecule level), especially when used as a powerful analytical tool for the detection of residual contaminants on versatile substrates.

Biodegradable aniline-derived electroconductive film for the regulation of neural stem cell fate.

Neural stem cells (NSCs) represent significant potential and promise in the treatment of neurodegenerative diseases and nerve injuries. An efficient methodology or platform that can help in specifically directing the stem cell fate is important and highly desirable for future clinical therapy. In this study, a biodegradable electrical conductive film composed of an oxidative polymerized carboxyl-capped aniline pentamer (CCAP) and ring-opening polymerized tetra poly(d,l-lactide) (4a-PLA) was designed with the addition of the dopant, namely chondroitin sulfate. This conductive film acts as a biological substrate for the exogenous/endogenous electric field transmission in tissue, resulting in the control of NSC fate, as well as improvement in neural tissue regeneration. The results show that CCAP is successfully synthesized and then conjugated onto 4a-PLA to form a network structure with electrical conductivity, cell adhesion capacity, and biodegradability. The neuronal differentiation of NSCs can be induced on 4a-PLAAP, and the neuronal maturation process can be facilitated by the manipulation of the electrical field. This biocompatible and electroactive material can serve as a platform to determine the cell fate of NSCs and be employed in neural regeneration. For future perspectives, its promising performance shows potential in applications, such as electrode-tissue integration interfaces, coatings on neuroprosthetics devices and neural probes, and smart drug delivery system in neurological systems.

Nanoparticle Delivery of MnO2 and Antiangiogenic Therapy to Overcome Hypoxia-Driven Tumor Escape and Suppress Hepatocellular Carcinoma.

Antiangiogenic therapy is widely administered in many cancers, and the antiangiogenic drug sorafenib offers moderate benefits in advanced hepatocellular carcinoma (HCC). However, antiangiogenic therapy can also lead to hypoxia-driven angiogenesis and immunosuppression in the tumor microenvironment (TME) and metastasis. Here, we report the synthesis and evaluation of NanoMnSor, a tumor-targeted, nanoparticle drug carrier that efficiently codelivers oxygen-generating MnO2 and sorafenib into HCC. We found that MnO2 not only alleviates hypoxia by catalyzing the decomposition of H2O2 to oxygen but also enhances pH/redox-responsive T1-weighted magnetic resonance imaging and drug-release properties upon decomposition into Mn2+ ions in the TME. Moreover, macrophages exposed to MnO2 displayed increased mRNA associated with the immunostimulatory M1 phenotype. We further show that NanoMnSor treatment leads to sorafenib-induced decrease in tumor vascularization and significantly suppresses primary tumor growth and distal metastasis, resulting in improved overall survival in a mouse orthotopic HCC model. Furthermore, NanoMnSor reprograms the immunosuppressive TME by reducing the hypoxia-induced tumor infiltration of tumor-associated macrophages, promoting macrophage polarization toward the immunostimulatory M1 phenotype, and increasing the number of CD8+ cytotoxic T cells in tumors, thereby augmenting the efficacy of anti-PD-1 antibody and whole-cell cancer vaccine immunotherapies. Our study demonstrates the potential of oxygen-generating nanoparticles to deliver antiangiogenic agents, efficiently modulate the hypoxic TME, and overcome hypoxia-driven drug resistance, thereby providing therapeutic benefit in cancer.

Photosynthesis-inspired H2 generation using a chlorophyll-loaded liposomal nanoplatform to detect and scavenge excess ROS.

A disturbance of reactive oxygen species (ROS) homeostasis may cause the pathogenesis of many diseases. Inspired by natural photosynthesis, this work proposes a photo-driven H2-evolving liposomal nanoplatform (Lip NP) that comprises an upconversion nanoparticle (UCNP) that is conjugated with gold nanoparticles (AuNPs) via a ROS-responsive linker, which is encapsulated inside the liposomal system in which the lipid bilayer embeds chlorophyll a (Chla). The UCNP functions as a transducer, converting NIR light into upconversion luminescence for simultaneous imaging and therapy in situ. Functioning as light-harvesting antennas, AuNPs are used to detect the local concentration of ROS for FRET biosensing, while the Chla activates the photosynthesis of H2 gas to scavenge local excess ROS. The results thus obtained indicate the potential of using the Lip NPs in the analysis of biological tissues, restoring their ROS homeostasis, possibly preventing the initiation and progression of diseases.

Food Quality Monitor: Paper-Based Plasmonic Sensors Prepared Through Reversal Nanoimprinting for Rapid Detection of Biogenic Amine Odorants.

This paper describes the fabrication of paper-based plasmonic refractometric sensors through the embedding of metal nanoparticles (NPs) onto flexible papers using reversal nanoimprint lithography. The NP-embedded papers can serve as gas sensors for the detection of volatile biogenic amines (BAs) released from spoiled food. Commercial inkjet papers were employed as sensor substrates-their high reflectance (>80%) and smooth surfaces (roughness: ca. 4.9 nm) providing significant optical signals for reflection-mode plasmonic refractometric sensing and high particle transfer efficiency, respectively; in addition, because inkjet papers have lightweight and are burnable and flexible, they are especially suitable for developing portable, disposable, cost-effective, eco-friendly sensing platforms. Solid silver NPs (SNPs), solid gold NPs (GNPs), and hollow Au-Ag alloyed NPs (HGNs) were immobilized on a solid mold and then transferred directly onto the softened paper surfaces. The particle number density and exposure height of the embedded NPs were dependent on two imprinting parameters: applied pressure and temperature. The optimal samples exhibited high particle transfer efficiency (ca. 85%), a sufficient exposure surface area (ca. 50% of particle surface area) presented to the target molecules, and a strong resonance reflectance dip for detection. Moreover, the HGN-embedded paper displayed a significant wavelength dip shift upon the spontaneous adsorption of BA vapors (e.g., Δλ = 33 nm for putrescine; Δλ = 24 nm for spermidine), indicating high refractometric sensitivity; in contrast, no visible spectroscopic responses were observed with respect to other possibly coexisting gases (e.g., air, N2, CO2, water vapor) during the food storage process, indicating high selectivity. Finally, the plasmonic sensing papers were used to monitor the freshness of a food product (salmon).

Near-IR-Absorbing Gold Nanoframes with Enhanced Physiological Stability and Improved Biocompatibility for In Vivo Biomedical Applications.

This paper describes the synthesis of near-infrared (NIR)-absorbing gold nanoframes (GNFs) and a systematic study comparing their physiological stability and biocompatibility with those of hollow Au-Ag nanoshells (GNSs), which have been used widely as photothermal agents in biomedical applications because of their localized surface plasmon resonance (LSPR) in the NIR region. The GNFs were synthesized in three steps: galvanic replacement, Au deposition, and Ag dealloying, using silver nanospheres (SNP) as the starting material. The morphology and optical properties of the GNFs were dependent on the thickness of the Au coating layer and the degree of Ag dealloying. The optimal GNF exhibited a robust spherical skeleton composed of a few thick rims, but preserved the distinctive LSPR absorbance in the NIR region-even when the Ag content within the skeleton was only 10 wt %, 4-fold lower than that of the GNSs. These GNFs displayed an attractive photothermal conversion ability and great photothermal stability, and could efficiently kill 4T1 cancer cells through light-induced heating. Moreover, the GNFs preserved their morphology and optical properties after incubation in biological media (e.g., saline, serum), whereas the GNSs were unstable under the same conditions because of rapid dissolution of the considerable silver content with the shell. Furthermore, the GNFs had good biocompatibility with normal cells (e.g., NIH-3T3 and hepatocytes; cell viability for both cells: >90%), whereas the GNSs exhibited significant dose-dependent cytotoxicity (e.g., cell viability for hepatocytes at 1.14 nM: ca. 11%), accompanied by the induction of reactive oxygen species. Finally, the GNFs displayed good biocompatibility and biosafety in an in vivo mouse model; in contrast, the accumulation of GNSs caused liver injury and inflammation. Our results suggest that GNFs have great potential to serve as stable, biocompatible NIR-light absorbers for in vivo applications, including cancer detection and combination therapy.

A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release.

The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer.

Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.

Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs)--PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis.

White-Light-Induced Collective Heating of Gold Nanocomposite/Bombyx mori Silk Thin Films with Ultrahigh Broadband Absorbance.

This paper describes a systematic investigation of the phenomenon of white-light-induced heating in silk fibroin films embedded with gold nanoparticles (Au NPs). The Au NPs functioned to develop an ultrahigh broadband absorber, allowing white light to be used as a source for photothermal generation. With an increase of the Au content in the composite films, the absorbance was enhanced significantly around the localized surface plasmon resonance (LSPR) wavelength, while non-LSPR wavelengths were also increased dramatically. The greater amount of absorbed light increased the rate of photoheating. The optimized composite film exhibited ultrahigh absorbances of approximately 95% over the spectral range from 350 to 750 nm, with moderate absorbances (>60%) at longer wavelengths (750-1000 nm). As a result, the composite film absorbed almost all of the incident light and, accordingly, converted this optical energy to local heat. Therefore, significant temperature increases (ca. 100 °C) were readily obtained when we irradiated the composite film under a light-emitting diode or halogen lamp. Moreover, such composite films displayed linear light-to-heat responses with respect to the light intensity, as well as great photothermal stability. A broadband absorptive film coated on a simple Al/Si Schottky diode displayed a linear, significant, stable photo-thermo-electronic effect in response to varying the light intensity.

Photothermal tumor ablation in mice with repeated therapy sessions using NIR-absorbing micellar hydrogels formed in situ.

Repeated cancer treatments are common, owing to the aggressive and resistant nature of tumors. This work presents a chitosan (CS) derivative that contains self-doped polyaniline (PANI) side chains, capable of self-assembling to form micelles and then transforming into hydrogels driven by a local change in pH. Analysis results of small-angle X-ray scattering indicate that the sol-gel transition of this CS derivative may provide the mechanical integrity to maintain its spatial stability in the microenvironment of solid tumors. The micelles formed in the CS hydrogel function as nanoscaled heating sources upon exposure to near-infrared light, thereby enabling the selective killing of cancer cells in a light-treated area. Additionally, photothermal efficacy of the micellar hydrogel is evaluated using a tumor-bearing mouse model; hollow gold nanospheres (HGNs) are used for comparison. Given the ability of the micellar hydrogel to provide spatial stability within a solid tumor, which prevents its leakage from the injection site, the therapeutic efficacy of this hydrogel, as a photothermal therapeutic agent for repeated treatments, exceeds that of nanosized HGNs. Results of this study demonstrate that this in situ-formed micellar hydrogel is a highly promising modality for repeated cancer treatments, providing a clinically viable, minimally invasive phototherapeutic option for therapeutic treatment.

Seed-mediated growth of gold nanocrystals: changes to the crystallinity or morphology as induced by the treatment of seeds with a sulfur species.

We report our observation of changes to the crystallinity or morphology during seed-mediated growth of Au nanocrystals. When single-crystal Au seeds with a spherical or rod-like shape were treated with a chemical species such as S2O3(2-) ions, twin defects were developed during the growth process to generate multiply twinned nanostructures. X-ray photoelectron spectroscopy analysis indicated that the S2O3(2-) ions were chemisorbed on the surfaces of the seeds during the treatment. The chemisorbed S2O3(2-) ions somehow influenced the crystallization of Au atoms added onto the surface during a growth process, leading to the formation of twin defects. In contrast to the spherical and rod-like Au seeds, the single-crystal structure was retained to generate a concave morphology when single-crystal Au seeds with a cubic or octahedral shape were used for a similar treatment and then seed-mediated growth. The different outcomes are likely related to the difference in spatial distribution of S2O3(2-) ions chemisorbed on the surface of a seed. This approach based on surface modification is potentially extendable to other noble metals for engineering the crystallinity and morphology of nanocrystals formed via seed-mediated growth.

2-[Anilino(diphenylphosphoryl)methyl]phenol from a three-component Kabachnik-Fields reaction.

The title compound, C25H22NO2P, was synthesized in high yield by a three-component Kabachnik-Fields reaction of diphenylphosphine oxide, salicylaldehyde and aniline in dry toluene at room temperature. It precipitates as racemic crystals, in which strong hydrogen bonds between the hydroxy group and the P=O group of a neighbouring molecule form one-dimensional heterochiral chains along the crystallographic a axis, with an O···O separation of 2.568 (2) Å. The pseudo-tetrahedral environment of the P atom is distorted, with O-P-C bond angles significantly larger than the C-P-C angles.