Hydrogel Nanoparticles Research Articles

No-core fiber interferometry pH sensor based on a polyvinyl alcohol/polyacrylic acid and silica/polyvinyl alcohol/polyacrylic acid hydrogel coating.

In this paper, we present an investigation on the sensing performance of a pH sensor based on a modal interferometer formed by a simple NO-core fiber interferometer (NCFI) that operates in transmission mode. The fundamental configuration of this sensor encompasses a single-mode-no-core-single-mode fiber (SMF-NCF-SMF "SNCS") segment chain. The chemical etching method has been used with hydrofluoric (HF) acid to prepare diverse NCF diameters. This was proposed to expand the evanescent fields and enhance sensor sensitivity. Then, the two diverse segments of etched NCF were cladded with polymeric composite fabricated by polyvinyl alcohol/polyacrylic acid (PVA/PAA) hydrogel and pure silica nanoparticles embedded in polyvinyl alcohol/polyacrylic acid (SiO2@PVA/PAA) hydrogel, respectively, for more sensing enhancement. Our results reveal that the PAA/PVA coating is a candidate coating material for acidic sensing, while SiO2@PVA/PAA is more appropriate for the base sensing, in which these coating materials show enhancement in the sensitivity above the NCF structure before an uncoated sensor due to greater enhancement of the evanescent field affected by the coating layer. The experimental results demonstrate a high average sensitivity of 3.42 nm/pH unit for the 11 w.t.% PVA/PAA coated sensor in the pH range from 1 to 7 and 3.2 nm/pH unit in the pH range from 8 to 14. The sensor also displays high repeatability and stability and low cross-sensitivity to temperature. The simple fabrication and high sensitivity of this sensor may prompt many potential applications in the fields of biology and chemistry.

Theranostic Design of Angiopep-2 Conjugated Hyaluronic Acid Nanoparticles (Thera-ANG-cHANPs) for Dual Targeting and Boosted Imaging of Glioma Cells.

Simple SummaryGlioblastoma multiforme is the most aggressive malignant brain tumor with poor patient prognosis. The presence of the blood-brain barrier and the complex tumor microenvironment impair the efficient accumulation of drugs and contrast agents, causing late diagnosis, inefficient treatment and monitoring. Functionalized theranostic nanoparticles are a valuable tool to modulate biodistribution of active agents, promoting their active delivery and selective accumulation for an earlier diagnosis and effective treatment, and provide simultaneous therapy and imaging for improved evaluation of treatment efficacy. In this work, we developed angiopep-2 functionalized crosslinked hyaluronic acid nanoparticles encapsulating gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and irinotecan (Thera-ANG-cHANPs) that were shown to boost relaxometric properties of Gd-DTPA by the effect of Hydrodenticity, improve the uptake of nanoparticles by the exploitation of angiopep-2 improved transport properties, and accelerate the therapeutic effect of Irinotecan.Glioblastoma multiforme (GBM) has a mean survival of only 15 months. Tumour heterogeneity and blood-brain barrier (BBB) mainly hinder the transport of active agents, leading to late diagnosis, ineffective therapy and inaccurate follow-up. The use of hydrogel nanoparticles, particularly hyaluronic acid as naturally occurring polymer of the extracellular matrix (ECM), has great potential in improving the transport of drug molecules and, furthermore, in facilitatating the early diagnosis by the effect of hydrodenticity enabling the T1 boosting of Gadolinium chelates for MRI. Here, crosslinked hyaluronic acid nanoparticles encapsulating gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and the chemotherapeutic agent irinotecan (Thera-cHANPs) are proposed as theranostic nanovectors, with improved MRI capacities. Irinotecan was selected since currently repurposed as an alternative compound to the poorly effective temozolomide (TMZ), generally approved as the gold standard in GBM clinical care. Also, active crossing and targeting are achieved by theranostic cHANPs decorated with angiopep-2 (Thera-ANG-cHANPs), a dual-targeting peptide interacting with low density lipoprotein receptor related protein-1(LRP-1) receptors overexpressed by both endothelial cells of the BBB and glioma cells. Results showed preserving the hydrodenticity effect in the advanced formulation and internalization by the active peptide-mediated uptake of Thera-cHANPs in U87 and GS-102 cells. Moreover, Thera-ANG-cHANPs proved to reduce ironotecan time response, showing a significant cytotoxic effect in 24 h instead of 48 h.

Thermal insulating and fire-retarding behavior of treated cotton fabrics with a novel high water-retaining hydrogel used in thermal protective clothing

Hydrogel-born fire resistance materials have attracted great attention due to their flame retardance and environmental friendliness. In this work, a facile strategy is presented to prepare a novel hydrogel–cotton fabric laminate with excellent thermal insulation and fire-retarding performance. The hydrogel–fabric laminates exhibited outstanding flame retardant behavior. The flame-retardant mechanism of this system was mainly due to the absorption of a large amount of energy as the water is heated and evaporated in the hydrogel layer. To increase the water retention capacity of the fire-resistant hydrogel, highly hydratable salt (CaCl2) was incorporated into the fire-resistant composite hydrogel composed of poly(N-isopropylacrylamide) (PNIPAAm)/sodium alginate (SA) to prolong water retention time. Here in this work, we aimed to investigate the effect of CaCl2 concentration on water retention capacity, fire-resistant and thermal insulating properties of hydrogel–cotton fabric laminates. Results indicated that the presence of hydratable salt successfully prolonged the water retention time and provided superior fire retardance property over traditional hydrogel. In additional, infrared imaging and vertical flammability test results confirmed that hydrogel–fabric laminates were capable of sustaining 1200 °C for 30 min without the cotton fabric layer burning, whereas natural cotton fabric was completely burned after 12 s. Finally, the hydrogel–cotton fabric laminates exhibited remarkable antibacterial activity against Staphylococcus aureus and Escherichia coli due to incorporated silver nanoparticles in hydrogels, and the bacteriostatic rates both exceeded 96%. The preparation of this hydrogel-born fire resistance materials is facile and can extended the period of protective time as fire resistant clothing for the firefighters.

Stimuli-Responsive, Plasmonic Nanogel for Dual Delivery of Curcumin and Photothermal Therapy for Cancer Treatment.

Nanogels (Ng) are crosslinked polymer-based hydrogel nanoparticles considered to be next-generation drug delivery systems due to their superior properties, including high drug loading capacity, low toxicity, and stimuli responsiveness. In this study, dually thermo-pH-responsive plasmonic nanogel (AuNP@Ng) was synthesized by grafting poly (N-isopropyl acrylamide) (PNIPAM) to chitosan (CS) in the presence of a chemical crosslinker to serve as a drug carrier system. The nanogel was further incorporated with gold nanoparticles (AuNP) to provide simultaneous drug delivery and photothermal therapy (PTT). Curcumin's (Cur) low water solubility and low bioavailability are the biggest obstacles to effective use of curcumin for anticancer therapy, and these obstacles can be overcome by utilizing an efficient delivery system. Therefore, curcumin was chosen as a model drug to be loaded into the nanogel for enhancing the anticancer efficiency, and further, its therapeutic efficiency was enhanced by PTT of the formulated AuNP@Ng. Thorough characterization of Ng based on CS and PNIPAM was conducted to confirm successful synthesis. Furthermore, photothermal properties and swelling ratio of fabricated nanoparticles were evaluated. Morphology and size measurements of nanogel were determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Nanogel was found to have a hydrodynamic size of ~167 nm and exhibited sustained release of curcumin up to 72 h with dual thermo-pH responsive drug release behavior, as examined under different temperature and pH conditions. Cytocompatibility of plasmonic nanogel was evaluated on MDA-MB-231 human breast cancer and non-tumorigenic MCF 10A cell lines, and the findings indicated the nanogel formulation to be cytocompatible. Nanoparticle uptake studies showed high internalization of nanoparticles in cancer cells when compared with non-tumorigenic cells and confocal microscopy further demonstrated that AuNP@Ng were internalized into the MDA-MB-231 cancer cells via endosomal route. In vitro cytotoxicity studies revealed dose-dependent and time-dependent drug delivery of curcumin loaded AuNP@Ng/Cur. Furthermore, the developed nanoparticles showed an improved chemotherapy efficacy when irradiated with near-infrared (NIR) laser (808 nm) in vitro. This work revealed that synthesized plasmonic nanogel loaded with curcumin (AuNP@Ng/Cur) can act as stimuli-responsive nanocarriers, having potential for dual therapy i.e., delivery of hydrophobic drug and photothermal therapy.

Biocompatible polypeptide nanogel: Effect of surfactants on nanogelation in inverse miniemulsion, in vivo biodistribution and blood clearance evaluation

Horseradish peroxidase (HRP)/H2O2-mediated crosslinking of polypeptides in inverse miniemulsion is a promising approach for the development of next-generation biocompatible and biodegradable nanogels. Herein, we present a fundamental investigation of the effects of three surfactants and their different concentrations on the (HRP)/H2O2-mediated nanogelation of poly[N5-(2-hydroxyethyl)-l-glutamine-ran-N5-propargyl-l-glutamine-ran-N5-(6-aminohexyl)-l-glutamine]-ran-N5-[2-(4-hydroxyphenyl)ethyl)-l-glutamine] (PHEG-Tyr) in inverse miniemulsion. The surfactants sorbitan monooleate (SPAN 80), polyoxyethylenesorbitan trioleate (TWEEN 85), and dioctyl sulfosuccinate sodium salt (AOT) were selected and their influence on the nanogel size, size distribution, and morphology was evaluated. The most effective nanogelation stabilization was achieved with 20 wt% nonionic surfactant SPAN 80. The diameter of the hydrogel nanoparticles was 230 nm (dynamic light scattering, DLS) and was confirmed also by nanoparticle tracking analysis (NTA) which showed the diameters ranging from 200 to 300 nm. Microscopy and image analyses showed that the nanogel in the dry state was spherical in shape and had number-average diameter Dn = 26 nm and dispersity Ð = 1.91. In the frozen-hydrated state, the nanogel appeared porous and was larger in size with Dn = 182 nm and Ð = 1.52. Our results indicated that the nanogelation of the polymer precursor required a higher concentration of surfactant than classical inverse miniemulsion polymerization to ensure effective stabilization. The developed polypeptide nanogel was radiolabeled with 125I, and in vivo biodistribution and blood clearance evaluations were performed. We found that the 125I-labeled nanogel was well-biodistributed in the bloodstream, cleared from mouse blood during 48 h by renal and hepatic pathways and did not provoke any sign of toxic effects.

Prolonged Codelivery of Hemagglutinin and a TLR7/8 Agonist in a Supramolecular Polymer-Nanoparticle Hydrogel Enhances Potency and Breadth of Influenza Vaccination.

The sustained release of vaccine cargo has been shown to improve humoral immune responses to challenging pathogens such as influenza. Extended codelivery of antigen and adjuvant prolongs germinal center reactions, thus improving antibody affinity maturation and the ability to neutralize the target pathogen. Here, we develop an injectable, physically cross-linked polymer–nanoparticle (PNP) hydrogel system to prolong the local codelivery of hemagglutinin and a toll-like receptor 7/8 agonist (TLR7/8a) adjuvant. By tethering the TLR7/8a to a NP motif within the hydrogels (TLR7/8a-NP), the dynamic mesh of the PNP hydrogels enables codiffusion of the adjuvant and protein antigen (hemagglutinin), therefore enabling sustained codelivery of these two physicochemically distinct molecules. We show that subcutaneous delivery of PNP hydrogels carrying hemagglutinin and TLR7/8a-NP in mice improves the magnitude and duration of antibody titers in response to a single injection vaccination compared to clinically used adjuvants. Furthermore, the PNP gel-based slow delivery of influenza vaccines led to increased breadth of antibody responses against future influenza variants, including a future pandemic variant, compared to clinical adjuvants. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of influenza subunit vaccines.

Nitric Oxide Releasing Hydrogel Nanoparticles Decreases Epithelial Cell Injuries Associated With Airway Reopening.

Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung condition. It is characterized by disruption of gas exchange inside the alveoli, accumulation of protein edema, and an increase in lung stiffness. One major cause of ARDS is a lung infection, such as SARS-COV-2 infection. Lungs of ARDS patients need to be mechanically ventilated for airway reopening. Consequently, ventilation might damage delicate lung tissue leading to excess edema, known as ventilator-induced lung injury (VILI). Mortality of COVID-19 patients under VILI seems to be higher than non-COVID patients, necessitating effective preventative therapies. VILI occurs when small air bubbles form in the alveoli, injuring epithelial cells (EPC) due to shear stress. Nitric oxide (NO) inhalation was suggested as a therapy for ARDS, however, it was shown that it is not effective because of the extremely short half-life of NO. In this study, NO-releasing nanoparticles were produced and tested in an in vitro model, representing airways in the deep lung. Cellular injuries were quantified via fluorescent live/dead assay. Atomic force microscopy (AFM) was used to assess cell morphology. qRT-PCR was performed to assess the expression of inflammatory markers, specifically IL6 and CCL2. ELISA was performed to assess IL6 and confirm qRT-PCR results at the protein level. Finally, ROS levels were assessed in all groups. Here, we show that NO delivery via nanoparticles enhanced EPC survival and recovery, AFM measurements revealed that NO exposure affect cell morphology, while qRT-PCR demonstrated a significant downregulation in IL6 and CCL2 expression when treating the cells to NO both before and after shear exposure. ELISA results for IL6 confirmed qRT-PCR data. ROS experiment results support our findings from previous experiments. These findings demonstrate that NO-releasing nanoparticles can be used as an effective delivery approach of NO to deep lung to prevent/reduce ARDS associated inflammation and cell injuries. This information is particularly useful to treat severe ARDS due to COVID-19 infection. These nanoparticles will be useful when clinically administrated to COVID-19 patients to reduce the symptoms originating from lung distress.

A Novel Urine Method for the Diagnosis of Active Tuberculosis by Immunoassay for the Detection of ESAT-6 Using Hydrogel Nanoparticles in HIV Patients

Background: In patients with HIV, conventional tests are of low sensitivity; therefore, a new diagnostic test with hydrogel nanoparticles with reactive blue dye is proposed, which allows the capture, conservation and concentration of ESAT-6 in urine. NIPAs are copolymers that capture low molecular weight proteins and protect against enzymatic degradation. Using an immunoassay, it is possible to detect and quantify ESAT-6 present in urine as a possible marker of active TB. Design/Methods: Study in Lima, Peru, HIV+ participants, ≥18 years with and without tuberculosis (TB). Smear microscopy, culture in solid medium and urine immunoassay were performed. The reference was the diagnosis of TB by radiological or clinical microbiological criteria (indication for TB treatment). There were 2 preanalytical processes: untreated and treated urine (centrifuged, heated), then incubation with NIPAm. After washing, elution, sonication, heat and centrifugation, the final eluate was obtained. This was placed on nitrocellulose membranes, which by means of fixation and incubation processes with anti-ESAT-6 and anti-IgG antibodies, revelation with C-DiGit&reg Blot Scanner and FluorChem R FR0001. Calibration curves were included in the membranes, density was measured using Image J software. ROC curves, sensitivity and specificity were obtained. Results: The result by groups was HIV+ patient: ROC: 0.75, cut-off point ≥24.06 ng/ml, sensitivity 76.32%, specificity 68.89%, patients ≤200 cells CD4 mm3/ml, ROC: 0.78, cutoff point ≥26.20 ng/ml, sensitivity 75.86%, specificity 71.88%, patients >200 CD4 mm3 cells/ml, ROC: 0.73, cutoff point ≥24.6 CD4 mm3/ml, sensitivity 73.68%, specificity 73.68%. Conclusions: The ESAT-6 detection assay using NIPAm was effective, with higher rates in patients with ≤200 CD4 cells/mm3, the test being more sensitive than smear and culture, but less specific.

Fabrication of hydrogels with nanoparticles as surface-enhanced Raman scattered (SERS) substrates and their application in Raman imaging

A polyvinyl alcohol–silver nanoparticle (PVA–Ag NP) hydrogel was fabricated using a simple and facile method; it was used as a substrate for surface-enhanced Raman scattering (SERS). The Ag+ ions dispersed uniformly in the PVA network were reduced by NaBH4; this process was termed dipping method. Compared with conventional SERS substrates (e.g., colloidal suspensions), the prepared PVA–Ag NP hydrogel has prominent Raman enhancement effects for crystal violet (CV), and the detection limit was 10−12 M. It could also help detect rhodamine B, methylene blue, and 4-mercaptobenzoic acid. In addition to SERS, the reliable 3D porous structure was utilized in the Raman imaging of CV at 1621 cm−1 in a nude mouse.

Controlled delivery of gold nanoparticle-coupled miRNA therapeutics via an injectable self-healing hydrogel.

Differential expression of microRNAs (miRNAs) plays a role in many diseases, including cancer and cardiovascular diseases. Potentially, miRNAs could be targeted with miRNA-therapeutics. Sustained delivery of these therapeutics remains challenging. This study couples miR-mimics to PEG-peptide gold nanoparticles (AuNP) and loads these AuNP-miRNAs in an injectable, shear thinning, self-assembling polymer nanoparticle (PNP) hydrogel drug delivery platform to improve delivery. Spherical AuNPs coated with fluorescently labelled miR-214 are loaded into an HPMC-PEG-b-PLA PNP hydrogel. Release of AuNP/miRNAs is quantified, AuNP-miR-214 functionality is shown in vitro in HEK293 cells, and AuNP-miRNAs are tracked in a 3D bioprinted human model of calcific aortic valve disease (CAVD). Lastly, biodistribution of PNP-AuNP-miR-67 is assessed after subcutaneous injection in C57BL/6 mice. AuNP-miRNA release from the PNP hydrogel in vitro demonstrates a linear pattern over 5 days up to 20%. AuNP-miR-214 transfection in HEK293 results in 33% decrease of Luciferase reporter activity. In the CAVD model, AuNP-miR-214 are tracked into the cytoplasm of human aortic valve interstitial cells. Lastly, 11 days after subcutaneous injection, AuNP-miR-67 predominantly clears via the liver and kidneys, and fluorescence levels are again comparable to control animals. Thus, the PNP-AuNP-miRNA drug delivery platform provides linear release of functional miRNAs in vitro and has potential for in vivo applications.

Hydrogel nanoparticle degradation influences the activation and survival of primary macrophages.

The effect of nanoparticle (NP) internalization on cell fate has emerged as an important consideration for nanomedicine design, as macrophages and other phagocytes are the primary clearance mechanisms of administered NP formulations. Pro-survival signaling is thought to be concurrent with phagocytosis and recent work has shown increased macrophage survival following lysosomal processing of internalized NPs. These observations have opened the door to explorations of NP physiochemical properties aimed at tuning the NP-driven macrophage survival at the lysosomal synapse. Here, we report that NP-induced macrophage survival and activation is strongly dependent on NP degradation rate using a series of thiol-containing poly(ethylene glycol) diacrylate-based NPs of equivalent size and zeta potential. Rapidly degrading, high thiol-containing NPs allowed for dramatic enhancement of cell longevity that was concurrent with macrophage stimulation after 2 weeks in ex vivo culture. While equivalent NP internalization resulted in suppressed caspase activity across the NP series, macrophage activation was correlated with increasing thiol content, leading to increased lysosomal activity and a robust pro-survival phenotype. Our results provide insight on tuning NP physiochemical properties as design handles for maximizing ex vivo macrophage longevity, which has implications for improving macrophage-based immune assays, biomanufacturing, and cell therapies.

Deoxyribonucleic acid polymer nanoparticle hydrogels.

Polymer nanoparticle hydrogels made of deoxyribonucleic acid and silica have been prepared and shown to display shear thinning and self-healing properties, sustained release of cargo and enzymatic degradation.

Injectable Self-Healing Hydrogels Containing CuS Nanoparticles with Abilities of Hemostasis, Antibacterial activity, and Promoting Wound Healing.

Injectable self-healing hydrogels containing functional nanoparticles (NPs) have attracted much attention in many fields of biomedicine. A series of injectable self-healing hydrogels containing PEGylation CuS NPs based on N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OA) were developed by taking advantages of the unique functions of CuS NPs and chitosan, referred to as CuS NP hydrogels or CEC-OAm-CuSn, where "m" stands for the concentration percentage of the added OA solution (w/v) and "n" represents the molar concentration of CuS NPs in the hydrogels. The physical properties of CuS NP hydrogels, syringeability, rapid self-repair ability, and photothermal performance were systematically investigated. The multiple functions for CuS NP hydrogels requested in the skin healing process were explored. The results showed that CuS NP hydrogels had not only adjustable physical properties and good injectable self-healing characteristics but also excellent functionalities, concurrently including hemostatic ability, bacteria killing capability, and cell migration and proliferation promotion. In vivo wound healing and histomorphological examinations of immunofluorescence staining in a mouse full-thickness wound model demonstrated good acceleration effects of these hydrogels for infected wound healing. Therefore, these injectable self-healing CuS NP hydrogels which possess the abilities of hemostasis, antibacterial activity, and infected-wound healing promotion exhibit great potential as in situ wound dressings.

Nanoparticle-based amelioration of drought stress and cadmium toxicity in rice via triggering the stress responsive genetic mechanisms and nutrient acquisition

Cadmium and drought are the most destructive of the abiotic stresses with negative consequences in terms of impaired metabolism, restricted nutrient use efficiency and disruptive photosynthesis of plants. The present study investigated the mitigation strategy of both aforementioned stresses by the application of iron oxide (IONPs) and hydrogel nanoparticles (HGNPs) simultaneously probably for the first time. IONPs were biofabricated by using a locally identified Bacillus strain RNT1, while HGNPs were produced chemically followed by the confirmation and characterization of both NPs through nanomaterials characterization techniques. Results of FTIR and XRD showed the capping of NPs by different functional groups together with their crystalline structure, respectively. SEM and TEM analysis showed the spherical shape along with the particle size ranging from 18 to 94 nm of both NPs, while EDS analysis confirmed the elemental purity of NPs. The results revealed that IONPs-treated rice plants increased biomass, antioxidant enzyme contents, photosynthesis efficiency, nutrient acquisition together with the decrease in reactive oxygen species and acropetal Cd translocation under normal and drought stress conditions as compared with control plants. Furthermore, the expression of the Cd transporter genes, OsHMA2, OsHMA3 and OsLCT1 were curtailed in NPs-treated rice plants under normal and drought stress conditions. The overall significance of the study lies in devising the NPs-based solutions of increasing heavy metal pollution and water availability challenges being faced the farmers around the world.

Hydrogel–Nanoparticle Hybrids for Biomedical Applications: Principles and Advantages

Hydrogel–Nanoparticle Hybrids for Biomedical Applications: Principles and Advantages

Fabrication of Hollow Channels Surrounded by Gold Nanoparticles in Hydrogel by Femtosecond Laser Irradiation.

The fabrication of hollow channels surrounded by gold nanoparticles in poly(ethylene glycol) diacrylate (PEGDA) is demonstrated. The absorption spectra show that gold nanoparticles were formed at the periphery of the focus by reduction of gold ions. The microscope observation and Raman spectroscopy analyses indicate that the center of the channels were void of PEGDA, which can be attributed to the femtosecond laser-induced degradation of the hydrogel. Since both the hydrogel and gold nanoparticles are biocompatible, this technique of fabricating hollow channels surrounded by gold nanoparticles is promising for tissue engineering, drug screening, and lab-on-a-chip devices.

1H NMR Relaxometric Study of Chitosan-Based Nanogels Containing Mono- and Bis-Hydrated Gd(III) Chelates: Clues for MRI Probes of Improved Sensitivity

Hydrogel nanoparticles composed of chitosan and hyaluronate and incorporating Gd-based MRI contrast agents with different hydration number (e.g., [Gd(DOTA)(H2O)]- and [Gd(AAZTA)(H2O)2]-) were prepared and fully characterized. In particular, 1H NMR relaxometric data, acquired as a function of temperature and applied magnetic field strength, were for the first time thoroughly analyzed using a theoretical model that includes the effects of a static zero-field splitting and an anisotropic molecular tumbling. The paramagnetic nanoparticles show excellent stability in aqueous solution for over 150 h and do not release the load of Gd(III) chelates. These nanoparticles exhibit enhanced efficacy (relaxivity) as relaxation agents, over 6 times that of the free complexes, thanks to the combination of a restricted molecular dynamics in the presence of a fast exchange of metal-bound water molecule(s) and between the water inside the nanogel and the bulk water. The knowledge of the molecular parameters that control the effectiveness of these MRI nanoprobes and those that limit their further increase will be crucial for the development of optimized systems with high sensitivity and stability.

Shotgun proteomics coupled to nanoparticle-based biomarker enrichment reveals a novel panel of extracellular matrix proteins as candidate serum protein biomarkers for early-stage breast cancer detection

BackgroundThe lack of specificity and high degree of false positive and false negative rates when using mammographic screening for detecting early-stage breast cancer is a critical issue. Blood-based molecular assays that could be used in adjunct with mammography for increased specificity and sensitivity could have profound clinical impact. Our objective was to discover and independently verify a panel of candidate blood-based biomarkers that could identify the earliest stages of breast cancer and complement current mammographic screening approaches.MethodsWe used affinity hydrogel nanoparticles coupled with LC-MS/MS analysis to enrich and analyze low-abundance proteins in serum samples from 20 patients with invasive ductal carcinoma (IDC) breast cancer and 20 female control individuals with positive mammograms and benign pathology at biopsy. We compared these results to those obtained from five cohorts of individuals diagnosed with cancer in organs other than breast (ovarian, lung, prostate, and colon cancer, as well as melanoma) to establish IDC-specific protein signatures. Twenty-four IDC candidate biomarkers were then verified by multiple reaction monitoring (LC-MRM) in an independent validation cohort of 60 serum samples specifically including earliest-stage breast cancer and benign controls (19 early-stage (T1a) IDC and 41 controls).ResultsIn our discovery set, 56 proteins were increased in the serum samples from IDC patients, and 32 of these proteins were specific to IDC. Verification of a subset of these proteins in an independent cohort of early-stage T1a breast cancer yielded a panel of 4 proteins, ITGA2B (integrin subunit alpha IIb), FLNA (Filamin A), RAP1A (Ras-associated protein-1A), and TLN-1 (Talin-1), which classified breast cancer patients with 100% sensitivity and 85% specificity (AUC of 0.93).ConclusionsUsing a nanoparticle-based protein enrichment technology, we identified and verified a highly specific and sensitive protein signature indicative of early-stage breast cancer with no false positives when assessing benign and inflammatory controls. These markers have been previously reported in cell-ECM interaction and tumor microenvironment biology. Further studies with larger cohorts are needed to evaluate whether this biomarker panel improves the positive predictive value of mammography for breast cancer detection.

A Novel Temperature‐Dependent Hydrogel Emulsion with Sol/Gel Reversible Phase Transition Behavior Based on Polystyrene‐co‐poly(N‐isopropylacrylamide)/Poly(N‐isopropylacrylamide) Core–Shell Nanoparticle

As a kind of temperature-responsive hydrogel, polystyrene-co-poly(N-isopropylacrylamide)/poly(N-isopropylacrylamide) (PS-co-PNIPAM/PNIPAM) core-shell nanoparticles prepared by two-step copolymerization are widely studied and used because of their specific structures and properties. Unlike most reports about the steady stability of PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion, in this work, the PS-co-PNIPAM/PNIPAM core-shell nanoparticle hydrogel emulsion (symbolized as PS/PNIPAM hydrogel emulsion), which is prepared after the second step of synthesis and without washing out a large number of PNIPAM polymer segments, shows a reversible temperature-dependent sol-gel transition characteristic during the temperature range of 34-80 °C. The PS/PNIPAM hydrogel emulsion is a normal solution at room temperature, and it changes from a sol to a gel statue when the temperature approaches up to low critical solution temperature (LCST). As the temperature continues to increase, the gel (core-shell nanoparticles as the crosslinkers and the linear PNIPAM chain as the 3D gel network) of the PS/PNIPAM hydrogel emulsion gradually shrinks and drains linearly. Compared with most crosslinked hydrogels, the hydrogel here can be arbitrarily changed in shape according to use needs, which is convenient for use, transportation, and storage. Here a new route is provided for the preparation of a PS/PNIPAM core-shell hydrogel nanoparticle system, as well as a new supramolecular crosslinking sol-gel system for application in biomedical materials, sensors, biological separation, drug release, macromolecular adsorption, and purification.

Scaling Laws in the Diffusive Release of Neutral Cargo from Hollow Hydrogel Nanoparticles: Paclitaxel-Loaded Poly(4-vinylpyridine).

We study the nonequilibrium diffusive release of electroneutral molecular cargo encapsulated inside hollow hydrogel nanoparticles. We propose a theoretical model that includes osmotic, steric, and short-range polymer-cargo attractions to determine the effective cargo-hydrogel interaction, ueff*, and the effective diffusion coefficient of the cargo inside the polymer network, Deff*. Using dynamical density functional theory (DDFT), we investigate the scaling of the characteristic release time, τ1/2, with the key parameters involved in the process, namely, ueff*, Deff*, and the swelling ratio. This effort represents a full study of the problem, covering a broad range of cargo sizes and providing predictions for repulsive and attractive polymer shells. Our calculations show that the release time through repulsive polymer networks scales with q2eβueff*/Deff* for βueff* ≫ 1. In this case, the cargo molecules are excluded from the shell of the hydrogel. For attractive shells, the polymer retains the cargo molecules on its internal surface and its interior, and the release time grows exponentially with the attraction strength. The DDFT calculations are compared to an analytical model for the mean first passage time, which provides an excellent quantitative description of the kinetics for both repulsive and attractive shells without fitting parameters. Finally, we apply the method to reproduce experimental results on the release of paclitaxel from hollow poly(4-vinylpyridine) nanoparticles and find that the slow release of the drug can be explained in terms of the strong binding attraction between the drug and the polymer.