PEG Nanoparticles Research Articles

Novel CeF3:Tm3+, Er3+ nanoparticles: NIR up-down conversion luminescence properties based on energy transfer of Tm3+ and Ce3+

A novel CeF3:Tm3+, Er3+ NIR up-down conversion luminescent nanoparticles with highly efficient visible and near-infrared second window (NIR-II) emission were synthesized by direct precipitation and hydrothermal methods. The two different emission modes of visible-NIR II light of Er3+were realized through the energy transfer of Tm3+ and Ce3+at the excitation wavelength of 808 nm. Which successfully combined the narrow emission peaks of visible light and the deep tissue penetration advantage of NIR-II. First, the effects of preparation conditions on the structure, morphology, stability and luminescence properties of CeF3:Tm3+, Er3+ nanoparticles were analyzed by XRD, SEM, TEM and PL. The results showed that the crystallinity, morphology and luminescence intensity of CeF3:Tm3+,Er3+ nanoparticles produced by hydrothermal method (reaction time of 10 h) were optimal compared with that of direct precipitation method. CeF3: Tm3+,Er3+ nanoparticles has better thermal stability, and fluorescence lifetime of 5D0→7F2 (525 nm), 4I15/2→4I11/2 (1066 nm) and 4I15/2→4I13/2 (1386 nm) for Er3+ are 15.51 ns, 48.78 us and 57.06 us, separately. At the same time, the surface of CeF3:Tm3+, Er3+ nanoparticles was modified by PEG and Lys. And then the effects of the surface modification on the hydration size, zeta potential and up-down conversion luminescent properties (visible and NIR-II light emission) were investigated. The results show that the modification of PEG effectively slows down the agglomeration of CeF3:Tm3+, Er3+ nanoparticles and improves their stability and dispersion under the same conditions. More importantly, the modification of PEG effectively increases the up-conversion luminescence intensity of CeF3:Tm3+, Er3+ nanoparticles under 808 nm excitation. Moreover, the CeF3:Tm3+, Er3+-PEG nanoparticles with 20–40 nm showed stronger NIR up-down conversion emission intensity in aqueous solutions (pH = 5,6,7) and better thermal stability. Furthermore, the CeF3:Tm3+, Er3+-PEG nanoparticles has low cytotoxicity and good biocompatibility. This study provides a theoretical basis for the development of high-performance rare-earth NIR up-down conversion luminescence materials.

Cysteine-modified PEGylated nanoparticles for targeted delivery of methylprednisolone to pancreatitis

The timely suppression of inflammatory mediator production and mitigation of their effects on pancreatic acinar cells are crucial for the successful management of acute pancreatitis. To achieve effective treatment, we present a novel approach utilizing cysteine modified PEG nanoparticles for both precise accumulation at the site of pancreatitis and specific targeting of acinar cells. Methylprednisolone, a nonsteroidal anti-inflammatory drug, was tailored to enhance its circulation time in the bloodstream, preferentially accumulate in the pancreas and enhance cell uptake efficiency by acinar cells through specifically targeting L-Type amino acid transporter 1. The nanosystem significantly downregulated pro-inflammatory cytokines in plasma, resulting in the effective suppression of inflammation in acinar cells within an acute pancreatitis rat model. The utilization of the dual targeted therapy strategy holds considerable potential for the clinical management of pancreatitis.

A novel intra-tumoral drug delivery carrier for treatment of oral squamous cell carcinoma

The treatment of oral squamous cell carcinoma (OSCC) includes systemic chemotherapy and is associated with aggressive side effects on patients. This study evaluated a new intra-tumor-targeted drug delivery method for the treatment of OSCC induced on the dorsum of the tongue in white mice. The induced tumors were examined by needle biopsy. A targeted anticancer drug (Cetuximab) and [Cisplatin and 5 Fluorouracil (5-FU)] chemotherapeutic agents were loaded on polyethylene glycol-polylactide-polyethylene glycol (PEG-PLA-PEG) nanoparticles (NPs) designed for intralesional injection while systemic administration was used as control. Fourier transform infrared spectroscopy (FTIR) was performed to study NP chemical structure, a drug release profile was conducted to study release kinetics, and histopathological evaluation was performed before and after treatment to evaluate tissue reactions (n-28, ά = 0.05). The drug release profile was characteristic of the chemotherapeutic agent showing early quick ascend followed by sustained slow release. FTIR peaks identified the polymeric structure of the drug nano-carrier. Histopathologic examination of chemically induced OSCC revealed different grades ranging from non-invasive to invasive stages of OSCC. Intra-tumoral test group revealed significant remission of observed cancer grade compared to the systemically administered group (X2 = 12.63, P < 0.001). Finally, using synthesized PEG–PLA–PEG NPs for intralesional injection is a promising route for the treatment of OSCC.

Construction of PEGylated chlorin e6@CuS-Pt theranostic nanoplatforms for nanozymes-enhanced photodynamic-photothermal therapy

Multifunctional nanoagents with photodynamic therapy (PDT) and photothermal therapy (PTT) functions have shown great promise for cancer treatment, while the design and synthesis of efficient nanoagents remain a challenge. To realize nanozyme-enhanced PDT-PTT combined therapy, herein we have synthesized the Ce6@CuS-Pt/PEG nanoplatforms as a model of efficient nanoagents. Hollow CuS nanospheres with an average diameter of ∼ 200 nm are first synthesized through vulcanization using Cu2O as the precursor. Subsequently, CuS nanospheres are surface-decorated with Pt nanoparticles (NPs) as nanozyme via an in-situ reduction route, followed by modifying the DSPE-PEG5000 and loading the photosensitizer Chlorin e6 (Ce6). The obtained Ce6@CuS-Pt/PEG NPs exhibit high photothermal conversion efficiency (43.08%), good singlet oxygen (1O2) generation ability, and good physiological stability. In addition, Ce6@CuS-Pt/PEG NPs show good catalytic performance due to the presence of Pt nanozyme, which can effectively convert H2O2 to O2 and significantly enhance the production of cytotoxic 1O2. When Ce6@CuS-Pt/PEG NPs dispersion is injected into mice, the tumors can be wholly suppressed owing to nanozyme-enhanced PDT-PTT combined therapy, providing better therapeutic effects compared to single-mode phototherapy. Thus, the present Ce6@CuS-Pt/PEG NPs can act as an efficient multifunctional nanoplatform for tumor therapy.

Abstract 3586: In vivo targeted detection and imaging of ovarian cancer by SPMR and MRI using anti-folate receptor functionalized iron oxide nanoparticles

Abstract Ovarian cancer is the second most common and most deadly gynecological cancer in women. Early and accurate detection is crucial in improving survival rate and quality of life of patients. Folate receptor alpha (FRα) is a folate transporter that has been reported to be overexpressed in approximately 90% of ovarian cancer, which makes it a suitable molecular target to use in developing tumor imaging methods. Iron oxide nanoparticles (NPs) have been used in a variety of cancer detection/imaging applications. Here we show that anti-FRα targeted superparamagnetic iron oxide nanoparticles (SPION) can be used for in vivo detection by two different imaging methods. Superparamagnetic Relaxometry (SPMR) is a highly sensitive in vivo detection technology that is able to differentiate the magnetic signature of nanoparticles bound to tumor cells from unbound nanoparticles. Same targeted SPIONs accumulated in tumor are able to provide molecular magnetic resonance imaging (MRI) contrast as well. Our results have shown that the anti-FRα NPs can distinguish high and low FRα expression cell lines, such as KB and A549, respectively in an in vitro cell based assay by SPMR, demonstrating good sensitivity, specificity and selectivity. In vivo study using xenograph model with KB and A549 cells implanted subcutaneously on the flank region of female athymic nude mice demonstrated higher level tumor accumulation of anti-FRα NPs in KB tumor compared to A549 tumor, measurable by ex vivo tumor detection using SPMR. Using a PEG NPs (without the target ligand) as control for the mice study have shown that minimum nanoparticle tumor accumulated were observed, demonstrating the specificity of the nanoparticles in vivo. Organ distribution study indicated that anti-FRα NPs mostly accumulated in liver and spleen as these nanoparticles were cleared through these two organs. Other organs such as brain, heart, lung, kidney didn’t show appreciable accumulation. The repeat of same type of xenograph mice model used in the SPMR study is currently under the way using MRI as an alternative in vivo detection method with images taken pre- and post- dosing of the nanoparticles. Based on the specificity and sufficient accumulation of nanoparticles demonstrated in the SPMR study, it is expected that MRI will show similar performance with additional anatomical information.Our anti-FRα NPs provided targeted and specific delivery to cancerous tissue and generated measurable signal by SPMR. Furthermore, demonstration of these anti-FRα NPs generating tumor specific contrast in MRI is currently under the way. These studies lay the groundwork for use of bio-safe magnetic particles as a detection and contrast agent for early ovarian cancer detection with improved accuracy to minimize the needs of invasive biopsies/surgery as well as potential utility for monitoring therapy response or recurrence. Citation Format: Marie Zhang, Kathirvel Kandasamy, Yamitha Perera, Dan Inglese, Eric Smith-Nguyen. In vivo targeted detection and imaging of ovarian cancer by SPMR and MRI using anti-folate receptor functionalized iron oxide nanoparticles. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3586.

Identification of fluorescently-barcoded nanoparticles using machine learning.

Barcoding of nano- and micro-particles allows distinguishing multiple targets at the same time within a complex mixture and is emerging as a powerful tool to increase the throughput of many assays. Fluorescent barcoding is one of the most used strategies, where microparticles are labeled with dyes and classified based on fluorescence color, intensity, or other features. Microparticles are ideal targets due to their relative ease of detection, manufacturing, and higher homogeneity. Barcoding is considerably more challenging in the case of nanoparticles (NPs), where their small size results in a lower signal and greater heterogeneity. This is a significant limitation since many bioassays require the use of nano-sized carriers. In this study, we introduce a machine-learning-assisted workflow to write, read, and classify barcoded PLGA-PEG NPs at a single-particle level. This procedure is based on the encapsulation of fluorescent markers without modifying their physicochemical properties (writing), the optimization of their confocal imaging (reading), and the implementation of a machine learning-based barcode reader (classification). We found nanoparticle heterogeneity as one of the main factors that challenges barcode separation, and that information extracted from the dyes' nanoscale confinement effects (such as Förster Resonance Energy Transfer, FRET) can aid barcode identification. Moreover, we provide a guide to reaching the optimal trade-off between the number of simultaneous barcodes and classification accuracy supporting the use of this workflow for a variety of bioassays.

Synergistic Release of Photothermal Molecules from Nanocarriers Induced by Light and Hyperthermia Benefits Efficient Anticancer Phototherapy.

Recently, nanoformulations have been widely applied in the delivery of organic photothermal agents (OPTAs) for cancer therapy to prolong blood circulation or improve tumor-targeting capacity. However, the systematic evaluations of their effects on the photothermal behavior of OPTAs are limited, especially for different types of nanoparticle systems. Herein, we prepared two kinds of nanoparticles (BSA and PEG nanoparticles (NPs)) to load an OPTA, a cyanine photosensitizer (IR780-O-TPE), and investigated their photothermal response, organelle targeting, and in vivo therapeutic efficacy. Due to different assembly forms, the two NPs showed distinct morphological changes after exposure to laser or hyperthermia. Under laser irradiation at 808 nm, BSA NPs could release IR780-O-TPE more efficiently than PEG NPs. We speculate that this phenomenon is probably caused by dual-responsive release of IR780-O-TPE from BSA NPs against light and hyperthermia. Moreover, IR780-O-TPE/BSA NPs were highly mitochondria-targeting and therefore displayed significant inhibition of cell viability. In contrast, IR780-O-TPE/PEG NPs were "shell-core" nanostructures and more stable under laser stimulation. As a consequence, the mitochondria-targeting and anticancer photothermal therapy by IR780-O-TPE/PEG NPs was less obvious. This study revealed the significance of nanocarrier design for OPTA delivery and demonstrated that BSA NPs could release IR780-O-TPE more effectively for efficient photothermal therapy. We also believe that the dual-responsive release of OPTAs from NPs can provide an effective strategy to promote anticancer photothermal treatment.

Engineering Poly(ethylene glycol) Nanoparticles for Accelerated Blood Clearance Inhibition and Targeted Drug Delivery.

Surface modification with poly(ethylene glycol) (PEGylation) is an effective strategy to improve the colloidal stability of nanoparticles (NPs) and is often used to minimize cellular uptake and clearance of NPs by the immune system. However, PEGylation can also trigger the accelerated blood clearance (ABC) phenomenon, which is known to reduce the circulation time of PEGylated NPs. Herein, we report the engineering of stealth PEG NPs that can avoid the ABC phenomenon and, when modified with hyaluronic acid (HA), show specific cancer cell targeting and drug delivery. PEG NPs cross-linked with disulfide bonds are prepared by using zeolitic imidazolate framework-8 NPs as templates. The reported templating strategy enables the simultaneous removal of the template and formation of PEG NPs under mild conditions (pH 5.5 buffer). Compared to PEGylated liposomes, PEG NPs avoid the secretion of anti-PEG antibodies and the presence of anti-PEG IgM and IgG did not significantly accelerate the blood clearance of PEG NPs, indicating the inhibition of the ABC effect for the PEG NPs. Functionalization of the PEG NPs with HA affords PEG NPs that retain their stealth properties against macrophages, target CD44-expressed cancer cells and, when loaded with the anticancer drug doxorubicin, effectively inhibit tumor growth. The innovation of this study lies in the engineering of PEG NPs that can circumvent the ABC phenomenon and that can be functionalized for the improved and targeted delivery of drugs.

Improve the cytotoxic effects of megavoltage radiation treatment by Fe3O4@Cus–PEG nanoparticles as a novel radiosensitizer in colorectal cancer cells

BackgroundTo enhance the performance of radiotherapy, emerging nanoparticles that can professionally enhance X-ray irradiation to destruct cancer cells are extremely necessary. Here, we examined the potential of PEG-coated magnetite copper sulfide hetero-nanoparticles (Fe3O4@Cus–PEG) as a radiosensitizer agent.MethodsFe3O4@Cus–PEG nanoparticles were synthesized and characterized. The toxicity of nanoparticles on HT-29 colorectal cancer cells was assessed by the MTT assay. The radio-sensitizing effects of Fe3O4@Cus–PEG nanoparticles on HT-29 cancer cells were investigated by the MTT and colony formation assays. Moreover, the underlying mechanisms for Fe3O4@Cus–PEG nanoparticles to improve the radiation sensitivity of cells were evaluated.ResultsThe results demonstrated that nanoparticles enhanced the effects of X-ray irradiation in a dose-dependent manner. The effects of combined treatments (nanoparticles and X-ray radiation) were strongly synergistic. The sensitizing enhancement ratio (SER) of nanoparticles was 2.02. Our in vitro assays demonstrated that the nitric oxide production, the intracellular hydrogen peroxide concentration, and the expression level of Bax and Caspase-3 genes significantly increased in the cells treated with the combination of nanoparticles and radiation. Whereas, the Glutathione peroxidase enzyme activity and the expression level of the Bcl-2 gene in the combined treatment significantly decreased compared to the radiation alone.ConclusionsOur study suggests that Fe3O4@Cus–PEG nanoparticles are the promising nano radio-sensitizing agents for the treatment of cancer cells to enhance the efficacy of radiation therapy through increasing the reactive oxygen species generation, nitric oxide production, and inducing apoptosis.Graphical

Biological Evaluation, Phytochemical Screening, and Fabrication of Indigofera Linifolia Leaves Extract-Loaded Nanoparticles.

Indigofera linifolia is a medicinally important plant, and by virtue of its rich phytochemical composition, this plant is widely used as essential component in traditional medication systems. Due to its wide range of medicinal applications, the extract-loaded chitosan (Ext+Ch), extract-loaded PEG (Ext+PEG), and extract-loaded locust bean gum (Ext+LGB) nanoparticles (NPs) were prepared in the present study. The prepared NPs were then evaluated for their antibacterial, antioxidant, and antidiabetic potentials. Antibacterial activities of the crude extract and the synthesized NPs were performed following standard procedures reported in the literature. The antioxidant capabilities of extract and NPs were evaluated using DPPH free radical scavenging assay. The antidiabetic potential of the samples was evaluated against α-amylase and α-glucosidase. Ext+PEG NPs showed more potent antibacterial activity against the selected strains of bacteria with the highest activity against Escherichia coli. The lowest antibacterial potential was observed for Ext+LGB NPs. The Ext+LGB NPs IC50 value of 39 μg/mL was found to be the most potent inhibitor of DPPH free radicals. Ext+LGB NPs showed a greater extent of inhibition against α-glucosidase and α-amylase with an IC50 of 83 and 78 μg/mL, whereas for the standard acarbose the IC50 values recorded against the mentioned enzymes were 69 and 74 μg/mL, respectively. A high concentration of phenolics and flavonoids in the crude extract was confirmed through TPC and TFC tests, HPLC profiling, and GC–MS analysis. It was considered that the observed antibacterial, antidiabetic, and antioxidant potential might be due the presence of these phenolics and flavonoids detected. The plant could thus be considered as a potential candidate to be used as a remedy of the mentioned health complications. However, further research in this regard is needed to isolate the exact responsible compounds of the observed biological potentials exhibited by the crude extract. Further, toxicity and pharmacological evaluations in animal models are also needed to establish the safety or toxicity profile of the plant.

Amentoflavone-loaded nanoparticles enhanced chemotherapy efficacy by inhibition of AKR1B10

Therapeutic nanoparticles can be combined with different anticancer drugs to achieve a synergistic therapy and avoid the limitations of traditional medicine and thus have clinical prospects for cancer. Herein, an effective nanoplatform was developed for self-assembling AMF@DOX-Fe3+-PEG nanoparticles (ADPF NPs) via the coordination of ferric ions (Fe3+), amentoflavone (AMF), doxorubicin (DOX), and PEG-polyphenol. The ADPF NPs possessed high drug loading efficiency, good stability and dispersion in water, prolonged blood circulation, and pH-dependent release, which leading to targeted drug transport and enhanced drug accumulation in the tumor. The AMF from the ADPF NPs could inhibit the expression of the Aldo-keto reductase family 1B10 (AKR1B10) and nuclear factor-kappa B p65 (NF-κB p65), which reduced the cardiotoxicity induced by DOX and enhanced the chemotherapy efficacy. This study established a new strategy of combining drug therapy with a nanoplatform. This new strategy has a wide application prospect in clinical tumor therapy.

Physisorption of Poly(ethylene glycol) on Inorganic Nanoparticles.

Poly(ethylene glycol) (PEG) is the most widely used polymer to decorate inorganic nanoparticles (NPs) by the "grafting-to" method for antifouling properties. PEG also shows diverse supramolecular interactions with nanoparticle surfaces and polar molecules, suggesting that the physisorption between PEG chains and NPs cannot be ignored in the "grafting-to" process. However, the effect of physisorption of PEG to NPs on the process of chemisorption has been rarely studied. Herein, we report that unfunctionalized PEG is physically adsorbed on various NPs by polyvalent supramolecular interactions, adopting "loop-and-train-tail" conformations. We investigated the effect of molecular weight of PEG and ligands of the NPs on the conformation of PEG chains by experimental methods and simulation. It is demonstrated that the physisorption of PEG on NPs can facilitate the chemisorption in the initial stages but delays it in the later stages during the "grafting-to" process. This work provides a deeper understanding of the conformation of physisorbed PEG on NPs and the relationship between physisorption and chemisorption.

Development of methods for fabricating nanoparticles composed of magnetite, gold, and silica toward diagnostic imaging

Nontoxic nanoparticle contrast agents with multiple imaging functions are required for medical diagnostic imaging, and coating the nanoparticle contrast agents with less toxic materials meets this requirement. This work proposes a method for fabricating magnetite, gold (Au), and silica nanoparticles toward diagnostic imaging. The proposed method involved four steps: the synthesis of magnetite (Fe3O4) nanoparticles, synthesis of Au nanoparticles, formation of a composite of Fe3O4 and Au (Fe3O4/Au), and silica coating of Fe3O4/Au nanoparticles. The synthesis of 6.3 ± 1.2 nm-sized Fe3O4 nanoparticles was performed via a salt-based reaction in an aqueous solution containing FeCl3, FeCl2, citric acid, HCl, and NaOH. The synthesis of 2.2 ± 0.4 nm-sized Au nanoparticles was performed with a reduction of HAuCl4 in an aqueous solution containing tetrakis (hydroxymethyl) phosphonium chloride, and NaOH. The silica coating of Fe3O4/Au nanoparticles was performed with a sol–gel reaction in ethanol containing Fe3O4 nanoparticles, Au nanoparticles, poly-diallyldimetheylammonium chloride, tetraethylorthosilicate, NaOH, and water under sonication. The Fe3O4/Au/SiO2 nanoparticles were degraded in a fetal bovine serum/phosphate-buffered saline solution, PEGylated Fe3O4/Au/SiO2 (Fe3O4/Au/SiO2–PEG) nanoparticles adsorbed protein after PEGylation, and Fe3O4/Au/SiO2–PEG nanoparticles had a magnetic property and an X-ray imaging ability, revealing that the composite nanoparticles were expected to function as a safe and excretable contrast agent of MRI and X-ray.

Evaluation of photocatalytic performances of PEG and PVP capped zinc sulfide nanoparticles towards organic environmental pollutant in presence of sunlight

Advanced oxidation processes triggered by nanoscale materials are promising owing to the in-situ generation of reactive radicals that can degrade toxic organic pollutants. In the present study, zinc sulfide (ZnS) nanoparticles with polyethylene glycol-4000 (PEG-4000) and polyvinylpyrrolidone (PVP) cappings were prepared using the chemical precipitation method and characterized thoroughly. Optical and structural characteristics of the capped ZnS nanoparticles were investigated and compared with those of uncapped ZnS nanoparticles. Results showed that PVP and PEG capped ZnS nanoparticles exhibited smaller crystallite size of 1.42 and 1.5 nm, respectively, as compared to uncapped ZnS (1.93 nm). Consequently, band gap energies of capped ZnS nanoparticles were higher which enable them to work as solar photocatalyst. The photocatalytic performance of the PEG, PVP-capped, and uncapped ZnS nanoparticles were evaluated against methyl orange (MO) dye and showed 85%, 87%, and 80% dye removal efficiencies, respectively. Degradation rate constant derived using Langmuir-Hinshelwood model revealed faster degradation kinetics bycapped ZnS photocatalysts owing to broader light absorption range. A possible dye degradation mechanism based on the energy levels positions was proposed to explain the route of photocatalytic degradation of MO by ZnS materials. It was inferred that the generation of reactive oxygen species by photogenerated electron-hole pairs facilitate degradation of MO dye molecules under sunlight illumination. It is expected that this work will provide insights into the development of strategies employed to achieve enhanced photocatalysis by nanoscale materials through organic capping.

Poly d,l-(lactic-co-glycolic) Acid PEGylated Isoliquiritigenin Alleviates Traumatic Brain Injury by Reversing Cyclooxygenase 2 Level.

As a severe neurological disease of trauma, traumatic brain injury (TBI) leads to other disorders, such as depression, dementia and epilepsy. This study investigated whether poly d,l-(lactic-co-glycolic) acid (PLGA) PEGylated isoliquiritigenin could alleviate TBI. One hundred and eighty-three patients with clinical brain trauma were divided into two groups with or without intracranial injury in magnetic resonance imaging. The clinical results showed that serum cyclooxygenase 2 (COX-2) levels were obviously increased in the TBI patients compared to the patients with head trauma only or healthy individuals. Intracranial injection of isoliquiritigenin in TBI rats reversed TBI induced increase of COX-2 level, significantly reduced water content and contusion volume. Our findings suggest that PLGA PEG nanoparticles loaded with isoliquiritigenin can achieve the same effects as intracranial administration of isoliquiritigenin in reducing serum COX-2 level.

Counterion-insulated near-infrared dyes in biodegradable polymer nanoparticles for in vivo imaging.

Polymeric nanoparticles (NPs) are highly attractive for biomedical applications due to their potential biodegradability and capacity to encapsulate different loads, notably drugs and contrast agents. For in vivo optical bioimaging, NPs should operate in the near-infrared region (NIR) and exhibit stealth properties. In the present work, we applied the approach of ionic dye insulation with bulky hydrophobic counterions for encapsulation of near-infrared cyanine dyes (Cy5.5 and Cy7 bearing two octadecyl chains) into biodegradable polymer (PLGA) NPs. We found that at high dye loading (20–50 mM with respect to the polymer), the bulkiest fluorinated tetraphenylborate counterion minimized best the aggregation-caused quenching and improved fluorescence quantum yields of both NIR dyes, especially of Cy5.5. In addition, bulky counterions also enabled formation of small 40 nm polymeric NPs in contrast to smaller counterions. To provide them stealth properties, we prepared 40 nm dye-loaded PEGylated NPs through nanoprecipitation of synthetic PLGA–PEG block copolymer with the dye/counterion salt. The obtained NIR NPs loaded with Cy5.5 dye salt allowed in vivo imaging of wild-type mice with a good contrast after IV injection. Compared to the bare PLGA NPs, PLGA–PEG NPs exhibited significantly slower accumulation in the liver. Biodistribution studies confirmed the preferential accumulation in the liver, although PLGA and PLGA–PEG NPs could also be distributed in other organs, with the following tendency: liver > spleen > lungs > kidney > heart > testis > brain. Overall, the present work validated the counterion approach for encapsulation of NIR cyanine dyes into biodegradable polymer NPs bearing covalently attached PEG shell. Thus, we propose a simple and robust methodology for preparation of NIR fluorescent biodegradable polymer NPs, which could further improve the existing optical imaging for biomedical applications.

Electrospinning of ternary composite of PMMA-PEG-SiO2 nanoparticles: Comprehensive process optimization and electrospun properties

Electrospinning has been realized to be a promising method for creating nano-composite fibers due to its significant growth for producing innovative composites with advanced applications. In this method a polymeric solution subjected to an electrohydrodynamic process and slim charged liquid jet is formed inside a high potential electric field. The high voltage enables the production of continuously long fibers on a collector surface. Addition of different polymers and NPs to the one-component solution to modify the physicochemical characteristic and decorating the surface of electrospun fibers has proven to be challenging and imperative for many fields especially novel bioengineering and filtration applications. In this study, the effects of major parameters on the fabrication of electrospun fibers were extensively investigated. At the first step, formation of nanofibers on the surface of collector and optimization of process parameters were determined based on the mean diameter of resulting fibers, through SEM (Scanning Electron Microscopy) images. The optimum values for concentration, applied voltage, the distance between the tip of needle and collector, and flow rate determined to be 10 wt%, 12 kV, 20 cm, and 0.6 mL h−1, respectively. Afterwards, the hydrophilicity of fibers was modified by adding different poly (ethylene glycol) (PEG) concentrations (20, 30, and 40 wt%) to the polymeric solution. The contact angle analysis revealed that the poly (methyl methacrylate) (PMMA) and 30 wt% PEG fabricated fibrous mat exhibited a better wettability and 71.61% lower hydrophobicity compared to pure PMMA electrospun mats. In the next step, silica NPs (nanoparticles) were introduced to the polymeric solution of electrospinning in the form of an IPA (isopropanol)-based collide solution. The dispersed solution-based addition of silica NPs prevented the aggregation state of NPs in the nanofibers. The addition of silica nanoparticles also changed the thermal and mechanical properties of the ternary composite, which were analyzed in TGA (thermogravimetric analysis) and tensile tests. Noteworthy, the addition of 30% PEG and silica NPs increase 3 times the tensile strength and around 2 times elongation in comparison with pure PMMA electrospun mats. These results highlight that the hybrid composite leads to a promising new electrospun mat for filtration and bioengineering applications.

SYNTHESIS AND CHARACTERIZATION OF PEG-CINNAMON ESSENTIAL OIL NANOPARTICLES AND THEIR APPLICATION AS AN INSECTICIDAL AGENT

The study deals with the EO-NPs encapsulated cinnamon essential oil for insecticidal activity. The prepared nanoparticles were subjected to characterization studies using Dynamic Light Scattering (DLS) analysis, Fourier Transform Infra-Red spectroscopy (FTIR) and Transmission Electron Microscopy (TEM) analysis. The DLS analysis revealed that the size of the nanoparticles had a slight increase in diameter after three months of storage. Similarly, the characterization with TEM showed that the prepared nanoparticles were of round or spherical shape with clear morphology without any crack in the external surface. Considerable mortality was observed from the insecticidal bioassay carried out by contact with cinnamon essential oil nanoparticles encapsulated with PEG (EO-NPs) against adult Oryzaephilus surinamensis (Linnaeus) (Coleoptra : Silvanidae). Further, the cinnamon EO-NPs also produced significant repellency effect on the adult insects. About 85% mortality (Contact Toxicity) was observed with 0.025 mg x cm2 concentration of EO-NPs. The results indicate that the cinnamon essential oil encapsulated with PEG nanoparticles could be an effective alternative to chemical pesticides for the control of stored product grain pests. Further this is the first report on the insecticidal efficacy of PEG encapsulated cinnamon essential oil against Oryzaephilus surinamensis.

MPEG-PLGA Nanoparticles Labelled with Loaded or Conjugated Rhodamine-B for Potential Nose-to-Brain Delivery.

Nowdays, neurodegenerative diseases represent a great challenge from both the therapeutic and diagnostic points of view. Indeed, several physiological barriers of the body, including the blood brain barrier (BBB), nasal, dermal, and intestinal barriers, interpose between the development of new drugs and their effective administration to reach the target organ or target cells at therapeutic concentrations. Currently, the nose-to-brain delivery with nanoformulations specifically designed for intranasal administration is a strategy widely investigated with the goal to reach the brain while bypassing the BBB. To produce nanosystems suitable to study both in vitro and/or in vivo cells trafficking for potential nose-to-brain delivery route, we prepared and characterized two types of fluorescent poly(ethylene glycol)-methyl-ether-block-poly(lactide-co-glycolide) (PLGA–PEG) nanoparticles (PNPs), i.e., Rhodamine B (RhB) dye loaded- and grafted- PNPs, respectively. The latter were produced by blending into the PLGA–PEG matrix a RhB-labeled polyaspartamide/polylactide graft copolymer to ensure a stable fluorescence during the time of analysis. Photon correlation spectroscopy (PCS), UV-visible (UV-vis) spectroscopies, differential scanning calorimetry (DSC), atomic force microscopy (AFM) were used to characterize the RhB-loaded and RhB-grafted PNPs. To assess their potential use for brain targeting, cytotoxicity tests were carried out on olfactory ensheathing cells (OECs) and neuron-like differentiated PC12 cells. Both PNP types showed mean sizes suitable for nose-to-brain delivery (<200 nm, PDI < 0.3) and were not cytotoxic toward OECs in the concentration range tested, while a reduction in the viability on PC12 cells was found when higher concentrations of nanomedicines were used. Both the RhB-labelled NPs are suitable drug carrier models for exploring cellular trafficking in nose-to-brain delivery for short-time or long-term studies.

Correlating Super-Resolution Microscopy and Transmission Electron Microscopy Reveals Multiparametric Heterogeneity in Nanoparticles.

The functionalization of nanoparticles with functional moieties is a key strategy to achieve cell targeting in nanomedicine. The interplay between size and ligand number is crucial for the formulation performance and needs to be properly characterized to understand nanoparticle structure–activity relations. However, there is a lack of methods able to measure both size and ligand number at the same time and at the single particle level. Here, we address this issue by introducing a correlative light and electron microscopy (CLEM) method combining super-resolution microscopy (SRM) and transmission electron microscopy (TEM) imaging. We apply our super-resCLEM method to characterize the relationship between size and ligand number and density in PLGA–PEG nanoparticles. We highlight how heterogeneity found in size can impact ligand distribution and how a significant part of the nanoparticle population goes completely undetected in the single-technique analysis. Super-resCLEM holds great promise for the multiparametric analysis of other parameters and nanomaterials.