Adsorptive Elimination of a Cationic Dye and a Hg (II)-Containing Antiseptic from Simulated Wastewater Using a Metal Organic Framework.

Several types of pollutants have acute adverse effects on living bodies, and the effective removal of these pollutants remains a challenge. Safranin O (a biological dye) and merbromin (a topical mercury-containing antiseptic) are considered organic pollutants, and there are only a few reports on their removal. Synthesized and well-characterized (through PXRD, FTIR, FESEM, and EDS analysis) MOF-5 was used for the first time in the removal of safranin O and merbromin from simulated wastewater and real wastewater. In both cases, MOF-5 effectively removed contaminants. We found that in simulated wastewater, the highest efficiency of removal of safranin O was 53.27% (for 15 mg/L) at pH 10, and for merbromin, it was 41.49% (for 25 mg/L) at pH 6. In the case of real wastewater containing natural ions (Na+, K+, F-, Cl-, SO42-, PO43-, Mg2+, and Ca2+) and other molecules, the removal efficiencies of these two dyes decreased (34.00% and 26.28% for safranin O and merbromin, respectively) because of the presence of other ions and molecules. A plausible mechanism for the removal of these pollutants using MOF-5 was proposed.

Tumor-homing peptide iRGD-conjugate enhances tumor accumulation of camptothecin for colon cancer therapy.

Poor intracellular uptake of therapeutics in the tumor parenchyma is a key issue in cancer therapy. We describe a novel approach to enhance tumor targeting and achieve targeted delivery of camptothecin (CPT) based on a tumor-homing internalizing RGD peptide (iRGD). We synthesized an iRGD-camptothecin conjugate (iRGD-CPT) covalently coupled by a heterobifunctional linker and evaluated its in vitro and in vivo activity in human colon cancer cells. In vitro studies revealed that iRGD-CPT penetrated cells efficiently and reduced colon cancer cell viability to a significantly greater extent at micromolar concentrations than did the parent drug. Furthermore, iRGD-CPT showed high distribution toward tumor tissue, effectively suppressed tumor progression, and showed enhanced antitumor effects relative to the parent drug in a mouse model, demonstrating that iRGD-CPT is effective in vivo cancer treatment. These results suggest that intracellular delivery of CPT via the iRGD peptide is a promising drug delivery strategy that will facilitate the development of CPT derivatives and prodrugs with improved efficacy.

Engineered Polymer-siRNA Polyplexes Provide Effective Treatment of Lung Inflammation.

Uncontrolled inflammation is responsible for acute and chronic diseases in the lung. Regulating expression of pro-inflammatory genes in pulmonary tissue using small interfering RNA (siRNA) is a promising approach to combatting respiratory diseases. However, siRNA therapeutics are generally hindered at the cellular level by endosomal entrapment of delivered cargo and at the organismal level by inefficient localization in pulmonary tissue. Here we report efficient anti-inflammatory activity in vitro and in vivo using polyplexes of siRNA and an engineered cationic polymer (PONI-Guan). PONI-Guan/siRNA polyplexes efficiently deliver siRNA cargo to the cytosol for highly efficient gene knockdown. Significantly, these polyplexes exhibit inherent targeting to inflamed lung tissue following intravenous administration in vivo. This strategy achieved effective (>70%) knockdown of gene expression in vitro and efficient (>80%) silencing of TNF-α expression in lipopolysaccharide (LPS)-challenged mice using a low (0.28 mg/kg) siRNA dosage.

Anticancer, Antibacterial, Antioxidant, and DNA-Binding Study of Metal-Phenalenyl Complexes.

Phenalenyl (PLY)-based metal complexes are a new addition to the metal complex family. Various applications of metal-based phenalenyl complexes (metal-PLY) have been reported, such as catalyst, quantum spin simulators, spin electronic devices, and molecular conductors, but the biological significance of metal-PLY (metal = Co(II), Mn(III), Ni(II), Fe(III), and Al(III)) systems has yet to be explored. In this study, the anticancer properties of such complexes were investigated in ovarian cancer cells (SKOV3 and HEY A8), and the cytotoxicity was comparable to that of other platinum-based drugs. Antibacterial activity of the metal-PLY complexes against both gram-negative (E. coli) and gram-positive (S. aureus) bacteria was studied using a disk diffusion test and minimum inhibitory concentration (MIC) methods. All five metal-PLY complexes showed significant antibacterial activity against both bacterial strains. The antioxidant properties of metal-PLY complexes were evaluated following the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging method and were acceptable. The DNA-binding properties of these metal-PLY complexes were investigated using absorption spectroscopy, fluorescence spectroscopy, viscosity measurements, and thermal denaturation methods. Experimental evidence revealed that the complexes bind to DNA through intercalation, and the molecular docking study supported this conclusion.

Mitochondria targeting molecular transporters: synthesis, lipophilic effect, and ionic complex.

As mitochondria are potential therapeutic targeting sites for the treatment of human diseases, delivering cytotoxic drugs, antioxidants, and imaging molecules to mitochondria can provide new therapeutic opportunities. In an attempt to develop a new mitochondria-targeting vector, we synthesized sorbitol-based molecular transporters with multiple guanidines, measured their partition coefficients, compared their targeting efficiency using fluorescent images and Pearson's correlation coefficients, and studied cellular uptake mechanisms. To increase the targeting ability of these molecular transporters to mitochondria, alanine-naphthalene as a lipophilic group was attached to the molecular transporter, which improved translocation across cellular membranes and led to higher accumulation in mitochondria. The molecular transporter was able to form an ionic complex with antibiotics, resulting in low cell viability. These data demonstrate that the molecular transporter with a lipophilic group could be utilized as a potential drug delivery vector for treating mitochondrial dysfunction.

Nanomaterial-based bioorthogonal nanozymes for biological applications.

Bioorthogonal transformations are chemical reactions that use pathways which biological processes do not access. Bioorthogonal chemistry provides new approaches for imaging and therapeutic strategies, as well as tools for fundamental biology. Bioorthogonal catalysis enables the development of bioorthogonal "factories" for on-demand and in situ generation of drugs and imaging tools. Transition metal catalysts (TMCs) are widely employed as bioorthogonal catalysts due to their high efficiency and versatility. The direct application of TMCs in living systems is challenging, however, due to their limited solubility, instability in biological media and toxicity. Incorporation of TMCs into nanomaterial scaffolds can be used to enhance aqueous solubility, improve long-term stability in biological environment and minimize cytotoxicity. These nanomaterial platforms can be engineered for biomedical applications, increasing cellular uptake, directing biodistribution, and enabling active targeting. This review summarizes strategies for incorporating TMCs into nanomaterial scaffolds, demonstrating the potential and challenges of moving bioorthogonal nanocatalysts and nanozymes toward the clinic.

Intracellular delivery of oxaliplatin conjugate via cell penetrating peptide for the treatment of colorectal carcinoma in vitro and in vivo.

Pt-based drugs are one of the main active agents in colorectal cancer treatment. However, drug resistance and dose-dependent side effects are the main barriers that restrict their clinical applications. As an alternative approach to these issues, we designed and synthesized a cell penetrating peptide (CPP) octaarginine-oxaliplatin conjugate that quickly and successfully delivered oxaliplatin into colon cancer cells. The CPP octaarginine is a well-studied cationic peptide that can play a role as a drug delivery vector. In this work, an octaarginine CPP (RRRRRRRR) was conjugated with oxaliplatin via a specific heterobifunctional linker. The in vitro studies showed the conjugate had affinity toward mitochondria inside cells and the MTT assay confirmed that conjugate is active in low micromolar range against colon cancer cells, requiring much lower concentrations than the oxaliplatin alone to reach IC50. More importantly, in the in vivo mouse study, the conjugate effectively inhibited tumor growth and showed considerably high antitumor activity, demonstrating the conjugate can perform well in vivo. This strategy may offer a new approach for designing oxaliplatin derivatives or prodrugs with remarkable therapeutic capabilities.

Silver-Based Nanomaterials as Therapeutic Agents Against Coronaviruses: A Review.

Since the identification of the first human coronavirus in the 1960s, a total of six coronaviruses that are known to affect humans have been identified: 229E, OC43, severe acute respiratory syndrome coronavirus (SARS-CoV), NL63, HKU1, and Middle East respiratory syndrome coronavirus (MERS-CoV). Presently, the human world is affected by a novel version of the coronavirus family known as SARS-CoV-2, which has an extremely high contagion rate. Although the infection fatality rate (IFR) of this rapidly spreading virus is not high (ranging from 0.00% to 1.54% across 51 different locations), the increasing number of infections and deaths has created a worldwide pandemic situation. To provide therapy to severely infected patients, instant therapeutic support is urgently needed and the repurposing of already approved drugs is presently in progress. In this regard, the development of nanoparticles as effective transporters for therapeutic drugs or as alternative medicines is highly encouraged and currently needed. The size range of the viruses is within 60-140 nm, which is slightly larger than the diameters of nanoparticles, making nanomaterials efficacious tools with antiviral properties. Silver-based nanomaterials (AgNMs) demonstrate antimicrobial and disinfectant effects mostly by generating reactive oxygen species (ROS) and are presently considered as a versatile tool for the treatment of COVID-19 patients. Other metal-based nanoparticles have been primarily reported as delivery agents or surface modifying agents, vaccine adjuvant against coronavirus. The present review summarizes and discusses the possible effectiveness of various surface-modified AgNMs against animal coronaviruses and presents a concept for AgNM-based therapeutic treatment of SARS-CoV-2 in the near future.

Green Synthesis, Characterization and Application of Natural Product Coated Magnetite Nanoparticles for Wastewater Treatment.

Adsorption of organic pollutants, toxic metal ions, and removal of harmful bacteria can give us clean and pure drinkable water from wastewater resources. Respective magnetite nanoparticles (MNPs) were synthesized using a cheaper and greener way in an open-air environment with the use of crude latex of Jatropha curcas (JC) and leaf extract of Cinnamomum tamala (CT). Characterization of MNPs had been performed by dynamic light scattering (DLS), Ultraviolet-visible (UV-vis) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, powdered X-ray diffraction (XRD), and field emission scanning electron microscope (FE-SEM). The size ranges of the synthesized MNPs were observed in between 20-42 nm for JC-Fe3O4 and within 26-35 nm for CT-Fe3O4 by FE-SEM images. The effect of synthesized magnetic nanoparticles in wastewater treatment (bacterial portion), dye adsorption, toxic metal removal as well as antibacterial, antioxidant, and cytotoxic activities were studied. This purification will lead to an increase in the resources of pure drinking water in the future.

Highly stretchable superhydrophobic surface by silica nanoparticle embedded electrospun fibrous mat.

HYPOTHESIS: Obtaining simultaneous stretchability and superhydrophobicity remains a great challenge in stretchable electronics, and wearable devices. Inspired by natural surfaces, such as lotus leaf, surface roughness and coating materials are the fundamental requirements to achieve superhydrophobicity. EXPERIMENTS: We prepared an elastic fibrous mat by electrospinning of a composite solution made of thermoplastic elastomer as an organic polymer matrix, and silica nanoparticles as inorganic additives to support surface roughness. To enhance hydrophobicity, the pristine mat was immersed into a solution of fluorinated material, which can decrease the surface energy. FINDINGS: The pristine fibrous mat showed high stretchability (with more than 1000% strain), and superhydrophobicity (with a contact angle of 156°, and a sliding angle of 7.8°). Superhydrophobicity did not disappear when the fibrous mat was stretched up to 1000%. Sliding angles were less than 10° under different strain levels only in longitudinal direction, suggesting the stretchable superhydrophobic surface is effective in rolling off the water droplet in one direction. The fibrous mat was repeatedly stretched 1000 times to 1000% strain; the material showed stable stretchability and superhydrophobicity. Based on these observations, the resulting fibrous mat appears to be in the Cassie-Baxter wetting state.

Versatility of cell-penetrating peptides for intracellular delivery of siRNA.

The plasma membrane is a large barrier to systemic drug delivery into cells, and it limits the efficacy of drug cargo. This issue has been overcome using cell-penetrating peptides (CPPs). CPPs are short peptides (6-30 amino acid residues) that are potentially capable of intracellular penetration to deliver drug molecules. CPPs broadened biomedical applications and provide a means to deliver a range of biologically active molecules, such as small molecules, proteins, imaging agents, and pharmaceutical nanocarriers, across the plasma membrane with high efficacy and low toxicity. This review is focused on the versatility of CPPs and advanced approaches for siRNA delivery.

Doxorubicin-loaded oligonucleotide conjugated gold nanoparticles: A promising in vivo drug delivery system for colorectal cancer therapy.

In this study, we propose doxorubicin (DOX) loaded oligonucleotides (ONTs) attached to gold nanoparticles (AuNPs) as a drug delivery system for cancer chemotherapy. DOX is one of the representative cancer chemotherapy agents and is widely used by many researchers as a chemotherapy agent in the drug delivery system. Due to the advantages of AuNPs such as simple steps in synthesis, high surface-area-to-volume ratio, and biocompatibility, we utilized AuNPs as drug delivery vehicle. AuNPs were synthesized by chemical reduction to be 13 nm diameter. The G-C rich oligonucleotides were used both for drug loading sites and AuNPs capping agents. 80% of DOX in solution could be bound to ONTs on AuNPs to became DOX-loaded AuNPs coated with ONTs (Doxorubicin-Oligomer-AuNP, DOA), and about 28% of loaded DOX was released from the as-prepared DOA. Confocal microscopy observation showed that DOA was well transported into cells, and finally the DOX was released into the cell nucleus. The drug's efficacies such as in vitro cytotoxicity and in vivo tumor growth inhibition were demonstrated with SW480 colon cancer cell line and a xenograft mouse model. MTT assay was performed to see the cytotoxicity effect on SW480 cells treated with DOA for 24 h, and the cell viability was determined to be 41.77% (p < 0.001). When DOA was administered regularly to a tumor bearing mouse, the tumor growth inhibition degree was examined by measuring the tumor size. The treatment-control (T/C) ratio was found to be 0.69. Thus, our results suggest the use of DOAs as promising drug delivery systems for colorectal cancer therapy.

Karyopherin α-2 is a reliable marker for identification of patients with high-risk stage II colorectal cancer.

PURPOSE: Adjuvant chemotherapy (AC) is frequently considered in patients with high-risk stage II colorectal cancer (CRC). Among patients with stage II CRC who do not receive AC because they are not considered to be at high risk, 20-25% will develop recurrence and die from the disease. Elevated levels of KPNA2 have been observed in various cancers, and overexpression of KPNA2 is related to CRC progression. METHODS: We examined the expression of KPNA2 using 293 CRC tissues, including 118 with stage II CRC, and investigated the applicability of KPNA2 as a biomarker to predict high-risk stage II CRC. Moreover, we further investigated the role of KPNA2 as an oncogene in CRC carcinogenesis using in vitro functional studies. RESULTS: High KPNA2 expression was associated with vascular (p = 0.027) and lymphatic invasion (p = 0.009) in patients with stage II CRC. On multivariate analysis, high KPNA2 expression (HR 3.174, 95% CI 2.060-4.889; p < 0.001) was independently associated with survival in patients with CRC. The overall survival rate in patients with high KPNA2 expression was higher than that in patients with low KPNA2 expression in CRC (p < 0.001), even in patients with stage II CRC (p = 0.001). Additionally, KPNA2 was associated with tumorigenesis and cancer progression in CRC cells; high KPNA2 expression was associated with increased cell proliferation (p < 0.05), migration (p = 0.03), invasion (p = 0.001), and semisolid agar colony formation (p < 0.001). CONCLUSION: KPNA2 expression is useful for identification of patients with high-risk stage II CRC who could benefit from AC and that KPNA2 may also be a promising therapeutic target.

Oncogenic function of angiopoietin-2 in vitro and its modulation of tumor progression in colorectal carcinoma.

Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its angiogenic function, and its role as an oncogene has yet to be elucidated. The current study hypothesized that Ang-2 may be an oncogene and have a function in tumor progression. An investigation of the function of Ang-2 in the LoVo colorectal cancer (CRC) cell line in vitro, which expresses a high level of Ang-2, was performed by knocking down endogenous expression with a targeted short hairpin RNA. The aggressive phenotypic effects of Ang-2 on experimental and control group cells were assessed using cell proliferation, migration and invasion assays. The association between Ang-2 expression levels and clinicopathological factors was evaluated in 415 CRC tissues using immunohistochemistry. Suppressing Ang-2 expression decreased cellular proliferation, invasion and migration in an in vitro study. Ang-2 overexpression was observed in 46% of patients with CRC and was significantly associated with pT (P=0.048), pN (P<0.001), venous invasion (P=0.023), lymphatic invasion (P<0.001) and tumor-node-metastasis stage (P=0.022). Furthermore, Ang-2 overexpression was an independent prognostic factor in pN stages 1 and 2. These results reveal that Ang-2 may be an oncogene in colorectal carcinogenesis and its expression may exert aggressive phenotypic effects during tumor progression. In addition, Ang-2 expression may serve as a prognostic marker and a potential drug target.

Intracellular and transdermal protein delivery mediated by non-covalent interactions with a synthetic guanidine-rich molecular carrier.

The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins. These ionic complexes were shown to have efficient cellular uptake properties. The optimum conditions including the molar ratio between cargo protein and carrier, and the treatment time have been defined. Several protein cargoes were successfully examined with differing sizes and molecular weights: green fluorescent protein (MW 27kDa), albumin (66kDa), concanavalin A (102kDa), and immunoglobulin G (150kDa). These non-covalent complexes were also found to have excellent transdermal penetration ability into the mouse skin. The skin penetration depth was studied histologically by light microscopy as well as two-photon microscopy thus generating a depth profile. These complexes were largely found in the epidermis and dermis layers, i.e. down to ca. 100µm depth of the mouse skin. Our synthetic Sor-G8 carrier was found to be substantially more efficient that Arg8 in both the intracellular transduction and the transdermal delivery of proteins. The mechanism of the cellular uptake of the complex was briefly studied, and the results suggested macropinocytosis.

RhoA is associated with invasion and poor prognosis in colorectal cancer.

Colorectal cancer is one of the most common cancers and is the fourth leading cause of cancer death in Korea. Mortality of colorectal cancer is strongly associated with the metastatic spread of the disease. As such, it is important to find and characterize signaling pathways involved in colon cancer metastasis. We investigated the functional importance of RhoA using human cell lines as well as 150 colorectal cancer patient-derived samples as it remains unclear whether RhoA functions as either an oncogene or a tumor suppressor in colon cancer. RhoA was highly expressed in metastatic cancer cell lines. Although cancer cell proliferation was only moderately impaired after depletion of RhoA, RhoA-depleted cancer cells exhibited markedly reduced migration and invasion ability in vitro. Furthermore, we found that RhoA is associated with the invasion of lymph nodes and blood vessels in the patient colorectal cancer samples. Most notably, patients with higher RhoA expression had a significantly poorer 5-year survival rate after surgery. These results suggest that RhoA is a marker of poor prognosis in colorectal cancer and may be a promising target for cancer treatment.

Novel multi-layered 1-D nanostructure exhibiting the theoretical capacity of silicon for a super-enhanced lithium-ion battery.

Silicon/carbon (Si/C) nanocomposites have recently received much attention as Li-ion battery negative electrodes due to their mutual synergetic effects in capacity and mechanical integrity. The contribution of Si to the total capacity of the Si/C nanocomposites determines their structural efficiency. Herein, we report on a multi-layered, one-dimensional nanostructure that exhibits the theoretical specific capacity of Si in the nanocomposite. Concentrically tri-layered, compartmentalized, C-core/Si-medium/C-shell nanofibers were fabricated by triple coaxial electrospinning. The pulverization of Si was accommodated inside the C-shell, whereas the conductive pathway of the Li-ions and electrons was provided by the C-core, which was proven by ex situ Raman spectroscopy. The compartmentalized Si in between the C-core and C-shell led to excellent specific capacity at a high current rate (>820 mA h g(-1) at 12000 mA g(-1)) and the realization of the theoretical specific capacity of the Li15Si4 phase of Si nanoparticles (3627 mA h g(-1)). The electrochemical characterization and inductively coupled plasma-atomic emission spectrometry provided direct evidence of full participation of Si in the electrochemical reactions.

Highly stretchable resistive pressure sensors using a conductive elastomeric composite on a micropyramid array.

A stretchable resistive pressure sensor is achieved by coating a compressible substrate with a highly stretchable electrode. The substrate contains an array of microscale pyramidal features, and the electrode comprises a polymer composite. When the pressure-induced geometrical change experienced by the electrode is maximized at 40% elongation, a sensitivity of 10.3 kPa(-1) is achieved.

Micropatterned stretchable circuit and strain sensor fabricated by lithography on an electrospun nanofiber mat.

This paper describes a novel approach for composite nanofiber mats and its application to fabricate a strain sensor. Electrospun poly(4-vinylpyridine) (P4VP) nanofiber mats are micropatterned by a lithographic approach that includes selective oxidation of the nanofibers and removal of unreacted fibers. The P4VP/HAuCl4 complex is converted to P4VP/Au composites by chemical reduction. We investigate the electrical resistivity of the composite mats according to the number of complexation-and-reduction cycles, the thickness of the fiber mats, and the annealing temperatures which control the percolation of the Au nanoparticles in the fiber mats. Nozzle printing of a polymeric solution on the patterned nanofiber mats simply produces an array of strain-sensitive and strain-invariant units. The patterns demonstrate high strain-sensing performance without any mechanical and electrical failure over 200 bending cycles in the strain range of ε<0.17.

Highly stretchable electric circuits from a composite material of silver nanoparticles and elastomeric fibres.

Conductive electrodes and electric circuits that can remain active and electrically stable under large mechanical deformations are highly desirable for applications such as flexible displays, field-effect transistors, energy-related devices, smart clothing and actuators. However, high conductivity and stretchability seem to be mutually exclusive parameters. The most promising solution to this problem has been to use one-dimensional nanostructures such as carbon nanotubes and metal nanowires coated on a stretchable fabric, metal stripes with a wavy geometry, composite elastomers embedding conductive fillers and interpenetrating networks of a liquid metal and rubber. At present, the conductivity values at large strains remain too low to satisfy requirements for practical applications. Moreover, the ability to make arbitrary patterns over large areas is also desirable. Here, we introduce a conductive composite mat of silver nanoparticles and rubber fibres that allows the formation of highly stretchable circuits through a fabrication process that is compatible with any substrate and scalable for large-area applications. A silver nanoparticle precursor is absorbed in electrospun poly (styrene-block-butadiene-block-styrene) (SBS) rubber fibres and then converted into silver nanoparticles directly in the fibre mat. Percolation of the silver nanoparticles inside the fibres leads to a high bulk conductivity, which is preserved at large deformations (σ ≈ 2,200 S cm(-1) at 100% strain for a 150-µm-thick mat). We design electric circuits directly on the electrospun fibre mat by nozzle printing, inkjet printing and spray printing of the precursor solution and fabricate a highly stretchable antenna, a strain sensor and a highly stretchable light-emitting diode as examples of applications.