Highly sensitive plasmonic paper substrate fabricated via amphiphilic polymer self-assembly in microdroplet for detection of emerging pharmaceutical pollutants.

We report an innovative and facile approach to fabricating an ultrasensitive plasmonic paper substrate for surface-enhanced Raman spectroscopy (SERS). The approach exploits the self-assembling capability of poly(styrene-b-2-vinyl pyridine) block copolymers to form a thin film at the air-liquid interface within the single microdroplet scale for the first time and the subsequent in situ growth of silver nanoparticles (AgNPs). The concentration of the block copolymer was found to play an essential role in stabilizing the droplets during the mass transfer phase and formation of silver nanoparticles, thus influencing the SERS signals. SEM analysis of the morphology of the plasmonic paper substrates revealed the formation of spherical AgNPs evenly distributed across the surface of the formed copolymer film with a size distribution of 47.5 nm. The resultant enhancement factor was calculated to be 1.2 × 107, and the detection limit of rhodamine 6G was as low as 48.9 pM. The nanohybridized plasmonic paper was successfully applied to detect two emerging pollutants-sildenafil and flibanserin-with LODs as low as 1.48 nM and 3.45 nM, respectively. Thus, this study offers new prospects for designing an affordable and readily available, yet highly sensitive, paper-based SERS substrate with the potential for development as a lab-on-a-chip device.

Cell penetrating peptides: Highlighting points in cancer therapy.

Cell-penetrating peptides (CPPs), first identified in HIV a few decades ago, deserved great attention in the last two decades; especially to support the penetration of anticancer drug means. In the drug delivery discipline, they have been involved in various approaches from mixing with hydrophobic drugs to the use of genetically conjugated proteins. The early classification as cationic and amphipathic CPPs has been extended to a few more classes such as hydrophobic and cyclic CPPs so far. Developing potential sequences utilized almost all methods of modern science: choosing high-efficiency peptides from natural protein sequences, sequence-based comparison, amino acid substitution, obtaining chemical and/or genetic conjugations, in silico approaches, in vitro analysis, animal experiments, etc. The bottleneck effect in this discipline reveals the complications that modern science faces in drug delivery research. Most CPP-based drug delivery systems (DDSs) efficiently inhibited tumor volume and weight in mice, but only in rare cases reduced their levels and continued further processes. The integration of chemical synthesis into the development of CPPs made a significant contribution and even reached the clinical stage as a diagnostic tool. But constrained efforts still face serious problems in overcoming biobarriers to reach further achievements. In this work, we reviewed the roles of CPPs in anticancer drug delivery, focusing on their amino acid composition and sequences. As the most suitable point, we relied on significant changes in tumor volume in mice resulting from CPPs. We provide a review of individual CPPs and/or their derivatives in a separate subsection.

Turn Off-On Fluorescent CO2 Gas Detection Based on Amine-Functionalized Imidazole-Based Poly(ionic liquid).

Poly(ionic liquids) (PILs) have been widely used for CO2 capture because their characteristics resemble those of an ionic liquid, yet they have properties typically associated with polymers. We studied the application of the amine-functionalized poly(vinylimidazole)-based PIL (PVIm-NH2) as a chemosensor. The PVIm-NH2 was successfully prepared by a facile and low-cost method and was characterized by several analytical techniques: proton nuclear magnetic resonance (1H NMR), Fourier transform infrared (FT-IR) spectroscopy, gel permeation chromatography (GPC), and spectrofluorometry. The ability of PVIm-NH2 to detect CO2 gas was evaluated in the presence of triethylamine (TEA). Under optimized conditions, the detection limit was calculated to be 2.86 × 10-3 M with R 2 = 0.9906. Moreover, theoretical and experimental studies suggested a plausible mechanism whereby PVIm-NH2 generates N-heterocyclic carbenes (NHCs) in the presence of TEA, which further reacts with CO2 gas in aqueous media to form a carboxylic acid. Analysis of PVIm-NH2 before and after the addition of TEA using the 1H NMR technique showed the disappearance of the proton peak, thus suggesting a successful generation of NHC. Further analysis via 13C NMR revealed the reaction of CO2 and NHC to form a carboxylic acid group. Finally, we demonstrated that PIL is a promising candidate as a chemosensor through diverse structural modifications.

Polymer-Based Hybrid Nanoarchitectures for Cancer Therapy Applications.

Globally, cancer is affecting societies and is becoming an important cause of death. Chemotherapy can be highly effective, but it is associated with certain problems, such as undesired targeting and multidrug resistance. The other advanced therapies, such as gene therapy and peptide therapy, do not prove to be effective without a proper delivery medium. Polymer-based hybrid nanoarchitectures have enormous potential in drug delivery. The polymers used in these nanohybrids (NHs)provide them with their distinct properties and also enable the controlled release of the drugs. This review features the recent use of polymers in the preparation of different nanohybrids for cancer therapy published since 2015 in some reputed journals. The polymeric nanohybrids provide an advantage in drug delivery with the controlled and targeted delivery of a payload and the irradiation of cancer by chemotherapeutical and photodynamic therapy.

Water-stable perovskite-loaded nanogels containing antioxidant property for highly sensitive and selective detection of roxithromycin in animal-derived food products.

Luminescent inorganic lead halide perovskite nanoparticles lack stability in aqueous solutions, limiting their application to optical sensors. Here, hybrid CsPbBr3-loaded MIP nanogels were developed with enhanced stability in aqueous media. Multifunctional MIP nanogels with antioxidant function and hydrophobic cavities were synthesized from HEMA derivatives in the presence of roxithromycin as a template. The CsPbBr3 nanoparticles were loaded into pre-synthesized MIP nanogels via in-situ synthesis with a size distribution of 200 nm. The developed CsPbBr3-nanogel exhibits excellent stability to air/moisture and enhanced stability toward an aqueous solvent. The developed CsPbBr3-loaded MIP nanogels showed a selective and sensitive detection of ROX with a limit of detection calculated to be 1.7 × 10-5 µg/mL (20.6 pM). The developed CsPbBr3-loaded MIP antioxidant-nanogels were evaluated on practical application for the quantitative determination of ROX antibiotic in animal-derived food products with excellent analytical performance. The detection of ROX in animal-derived food products showed good recovery results, making them an ideal candidate for sensing ROX.

Selective optosensing of iron(III) ions in HeLa cells using NaYF4:Yb3+/Tm3+ upconversion nanoparticles coated with polyepinephrine.

Novel polyepinephrine-modified NaYF4:Yb,Tm upconversion luminescent nanoparticles (UCNP@PEP) were prepared via the self-polymerization of epinephrine on the surfaces of the UCNPs for selective sensing of Fe3+ inside a cell and for intracellular imaging. The proposed UCNP@PEP probe is a strong blue light emitter (λmax = 474 nm) upon exposure to an excitation wavelength of 980 nm. The probe was used for detecting Fe3+ owing to the complexation reaction between UCNP@PEP and Fe3+, resulting in reduced upconversion luminescence (UCL) intensity. The proposed probe has a detection limit of 0.2 µM and a good linear range of 1-10 µM for sensing Fe3+ ions. Moreover, the UCNP@PEP probe displays high cell viability (90%) and is feasible for intracellular imaging. The ability of the probe to sense Fe3+ in a human serum sample was tested and shows promising output for diagnostic purposes. The prepared UCNP@PEP probe was characterized by using UV-visible (UV-Vis) absorption spectrometry, fluorescence (FL) spectrometry, field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FT-IR).

Solvent-resistant microfluidic paper-based analytical device/spray mass spectrometry for quantitative analysis of C18 -ceramide biomarker.

We developed a highly efficient and low-cost organic solvents-resistant microfluidic paper-based analytical device (µPAD) coupled with paper spray mass spectrometry (PS-MS) for quantitative determination of C18 -ceramide as a prognostic biomarker for several diseases. Several models of µPAD patterns have been examined to select the most resistant and efficient microchannel barriers, which can provide continuous spray at ionization zone and prevent "coffee ring" effect. Moreover, the developed µPAD has enabled the analysis of low concentration of C18 -ceramide because of the maximum supply of deposited analyte through microchannel. The MS results confirmed the formation of doubly and singly charged metal ion complexes between ceramide and different metal ions. Notably, the complexation that occurs between lithium ions and C18 -ceramide showed a high relative abundance compared with other formed complexes. Taking into account the relative abundance of complex [Cer + Li]+ at 572.8 m/z, it can be considered as a stable ion and therefore be used for the analysis of C18 -ceramide at low concentrations. Complexation of C18 -ceramide and lithium confirmed with quantum chemical calculations. The proposed method represents good linearity with a regression coefficient of 0.9956 for the analysis of C18 -ceramide and reaches a limit of detection to 0.84 nM. It has been adapted successfully for practical application in human serum samples with high recovery values in range of 92%-105%. The developed µPAD-MS technique provides clear advantages by reducing the experimental steps and simplifying the operation process and enables to identify subnanomolar concentration of C18 -ceramide in human serum samples.

Dual emission nonionic molecular imprinting conjugated polythiophenes-based paper devices and their nanofibers for point-of-care biomarkers detection.

Enzyme-based assays have been extensively used for the early diagnosis of disease-related biomarkers. However, these assays are time-consuming, resource-intensive, and infrastructure-dependent, which renders them unsuitable and impractical for use in resource-constrained areas. Thus, there is a strong demand for a biocompatible and potentially generalizable sensor that can rapidly detect cancer biomarkers at ultralow concentration. Herein, an enzyme-free, cost-efficient, and easy-to-use assay based on a novel approach that entails fluorescent molecularly imprinting conjugated polythiophenes (FMICPs) for cancer biomarkers detection is developed. The promising conjugated polythiophenes structure, with a PLQY as high as 55%, provides a straightforward, and affordable method for free-enzyme signal generation. More importantly, the feasibility of integrating printed-paper technology with a sensitive and cost-effective smartphone and portable prototype testing device that could be utilized for rapid point-of-care (POC) cancer diagnostics is successfully introduced. Significantly, the unique structure of FMICP nanofibers (FMICP NFs) displays superior performance with enhanced sensitivity that is 80 times higher than that of pristine FMICP. This assay could lower the limits of detection to 15 fg mL-1 and 3.5 fg mL-1 for α-fetoprotein (AFP) and carcinoembryonic antigen (CEA), respectively, which are three orders of magnitude exceeding that of the standard enzyme-based assay. Moreover, the developed sensors are successfully applied to the fast diagnosis of AFP in liver cancer patients and the FMICP and FMICP NFs results are in excellent agreement with those of clinical ELISA.

Recent Advances in Nanomicelles Delivery Systems.

The efficient and selective delivery of therapeutic drugs to the target site remains the main obstacle in the development of new drugs and therapeutic interventions. Up until today, nanomicelles have shown their prospective as nanocarriers for drug delivery owing to their small size, good biocompatibility, and capacity to effectively entrap lipophilic drugs in their core. Nanomicelles are formed via self-assembly in aqueous media of amphiphilic molecules into well-organized supramolecular structures. Molecular weights and structure of the core and corona forming blocks are important properties that will determine the size of nanomicelles and their shape. Selective delivery is achieved via novel design of various stimuli-responsive nanomicelles that release drugs based on endogenous or exogenous stimulations such as pH, temperature, ultrasound, light, redox potential, and others. This review summarizes the emerging micellar nanocarriers developed with various designs, their outstanding properties, and underlying principles that grant targeted and continuous drug delivery. Finally, future perspectives, and challenges for nanomicelles are discussed based on the current achievements and remaining issues.

Multiple Emitting Amphiphilic Conjugated Polythiophenes-Coated CdTe QDs for Picogram Detection of Trinitrophenol Explosive and Application Using Chitosan Film and Paper-Based Sensor Coupled with Smartphone.

Novel multiple emitting amphiphilic conjugated polythiophene-coated CdTe quantum dots for picogram level determination of the 2,4,6-trinitrophenol (TNP) explosive are developed. Four biocompatible sensors, cationic polythiophene nanohybrids (CPTQDs), nonionic polythiophene nanohybrids (NPTQDs), anionic polythiophene nanohybrids (APTQDs), and thiophene copolymer nanohybrids (TCPQDs), are designed using an in situ polymerization method, which shows highly enhanced fluorescence intensity and quantum yield (up to 78%). All sensors are investigated for nitroexplosive detection to provide a remarkable fluorescence quenching for TNP and the quenching efficiency reached 96% in the case of TCPQDs. The fluorescence of the sensors are quenched by TNP through inner filter effect, electrostatic, π-π, and hydrogen bonding interactions. Under optimal conditions, the detection limits of CPTQDs, NPTQDs, APTQDs, and TCPQDs are 2.56, 7.23, 4.12, and 0.56 × 10-9 m, respectively, within 60 s. More importantly, portable, cost effective, and simple to use paper strips and chitosan film are successfully applied to visually detect as little as 2.29 pg of TNP. The possibility of utilizing a smartphone with a color-scanning APP in the determination of TNP is also established. Moreover, the practical application of the developed sensors for TNP detection in tap and river water samples is described with satisfactory recoveries of 98.02-107.50%.

One-step synthesis of NaLu80-xGdxF4:Yb183+/Er23+(Tm3+) upconversion nanoparticles for in vitro cell imaging.

Upconversion nanoparticles (UCNPs) possess a unique type of photoluminescence (PL) in which lower-energy excitation is converted into higher-energy emission via multi-photon absorption processes. In this work, we have used a facile one-step hydrothermal method promoted water solubility to synthesis NaLuGdF4:Yb3+/Er3+(Tm3+) UCNPs coated with malonic acid (MA). Scanning electron microscopy images and X-ray diffraction patterns reveal sphere-shaped UCNPs with an average size of ~80nm crystallized in the cubic NaLuF4 structure. The characteristic vibrations of cubic UCNPs have been taken into account by using Fourier-transform infrared spectroscopy. Based on PL studies, we have determined an optimal concentration of Gd3+ doping. The dependence of upconversion PL intensity on Gd3+ concentration is discussed via the results of magnetization measurements, which is related to the coupling/uncoupling of Gd3+ ions. Particularly, our study reveals that carboxyl-functionalized NaLuGdF4:Yb3+/Er3+(Tm3+) UCNPs have a relatively high cell viability with HeLa cells.

Phospholipase A2-Responsive Phosphate Micelle-Loaded UCNPs for Bioimaging of Prostate Cancer Cells.

We report the effective synthesis of biocompatible upconversion nanoparticles (UCNP)-loaded phosphate micelles and successful delivery of UCNPs to prostate cancer cells via secreted phospholipase A2 (sPLA-2) enzyme cleavage of the loaded micelles for the first time. The activity of the (sPLA-2) enzyme toward the synthesized micelles was investigated and confirmed by LC-MS. TEM results showed that the micelles have a size distribution of 80 to 150 nm, whereas UCNP-loaded micelles range from 200 to 350 nm, indicating the successful loading of UCNPs. The selective release of UCNPs to prostate cancer cells rather than other cells, specifically cervical cancer cells, was observed and confirmed by a range of bioimaging studies. Moreover, cytotoxicity assays confirmed the biocompatibility of the UCNP-loaded micelles.

Yb3+,Er3+,Eu3+-codoped YVO4 material for bioimaging with dual mode excitation.

We propose an efficient bioimaging strategy using Yb3+,Er3+,Eu3+-triplet doped YVO4 nanoparticles which were synthesized with polymer as a template. The obtained particles possess nanoscale, uniform, and flexible excitation. The effect of Eu3+ ions on the luminescence properties of YVO4:Yb3+,Er3+,Eu3+ was investigated. The upconversion mechanism of the prepared material was also discussed. The structure and optical properties of the prepared material were characterized by using X-ray diffraction (XRD), Fourier-transform IR spectroscopy (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM) upconversion and photoluminescence spectra. The Commission International de I'Eclairage (CIE) chromaticity coordinates was investigated to confirm the performance of color luminescent emission. The prepared YVO4:Yb3+,Er3+,Eu3+ nanoparticles could be easily dispersed in water by surface modification with cysteine (Cys) and glutathione (GSH). The aqueous dispersion of the modified YVO4:Yb3+,Er3+,Eu3+ exhibits bright upconversion and downconversion luminescence and has been applied for bioimaging of HeLa cells. Our developed material with dual excitation offers a promising advance in bioimaging.