Bioaerosol size as a potential determinant of airborneE. coliviability under ultraviolet germicidal irradiation and ozone disinfection.

Ultraviolet germicidal irradiation (UVGI) and ozone disinfection are crucial methods for mitigating the airborne transmission of pathogenic microorganisms in high-risk settings, particularly with the emergence of respiratory viral pathogens such as SARS-CoV-2 and avian influenza viruses. This study quantitatively investigates the influence of UVGI and ozone on the viability ofE. coliin bioaerosols, with a particular focus on howE. coliviability depends on the size of the bioaerosols, a critical factor that determines deposition patterns within the human respiratory system and the evolution of bioaerosols in indoor environments. This study used a controlled small-scale laboratory chamber whereE. colisuspensions were aerosolized and subjected to varying levels of UVGI and ozone levels throughout the exposure time (2-6 s). The normalized viability ofE. coliwas found to be significantly reduced by UVGI (60-240µW s cm-2) as the exposure time increased from 2 to 6 s, and the most substantial reduction ofE. colinormalized viability was observed when UVGI and ozone (65-131 ppb) were used in combination. We also found that UVGI reduced the normalized viability ofE. coliin bioaerosols more significantly with smaller sizes (0.25-0.5µm) than with larger sizes (0.5-2.5µm). However, when combining UVGI and ozone, the normalized viability was higher for smaller particle sizes than for the larger ones. The findings provide insights into the development of effective UVGI disinfection engineering methods to control the spread of pathogenic microorganisms in high-risk environments. By understanding the influence of the viability of microorganisms in various bioaerosol sizes, we can optimize UVGI and ozone techniques to reduce the potential risk of airborne transmission of pathogens.

Cell-Penetrating Peptides for Use in Development of Transgenic Plants.

Genetically modified plants and crops can contribute to remarkable increase in global food supply, with improved yield and resistance to plant diseases or insect pests. The development of biotechnology introducing exogenous nucleic acids in transgenic plants is important for plant health management. Different genetic engineering methods for DNA delivery, such as biolistic methods, Agrobacterium tumefaciens-mediated transformation, and other physicochemical methods have been developed to improve translocation across the plasma membrane and cell wall in plants. Recently, the peptide-based gene delivery system, mediated by cell-penetrating peptides (CPPs), has been regarded as a promising non-viral tool for efficient and stable gene transfection into both animal and plant cells. CPPs are short peptides with diverse sequences and functionalities, capable of agitating plasma membrane and entering cells. Here, we highlight recent research and ideas on diverse types of CPPs, which have been applied in DNA delivery in plants. Various basic, amphipathic, cyclic, and branched CPPs were designed, and modifications of functional groups were performed to enhance DNA interaction and stabilization in transgenesis. CPPs were able to carry cargoes in either a covalent or noncovalent manner and to internalize CPP/cargo complexes into cells by either direct membrane translocation or endocytosis. Importantly, subcellular targets of CPP-mediated nucleic acid delivery were reviewed. CPPs offer transfection strategies and influence transgene expression at subcellular localizations, such as in plastids, mitochondria, and the nucleus. In summary, the technology of CPP-mediated gene delivery provides a potent and useful tool to genetically modified plants and crops of the future.

3D-printed hydrogels dressings with bioactive borate glass for continuous hydration and treatment of second-degree burns.

Recent advances in additive manufacturing have led to the development of innovative solutions for tissue regeneration. Hydrogel materials have gained significant attention for burn wound treatment in clinical practice among various advanced dressings due to their soothing and moisturizing activity. However, prolonged healing, pain, and traumatic removal due to the lack of long-term wound hydration are some of the challenges in the treatment of second-degree burn wounds. In this study, 3D-printed dressings were fabricated using gelatin, alginate, and bioactive borate glass (BBG) using an extrusion-based bioprinter. After ionic crosslinking, the 3D-printed dressings were characterized for mechanical properties, degradation rate, hydration activity, and in vitro cell viability using human fibroblasts. The results demonstrated that in 3D-printed dressings with 20 wt% BBG, Young's modulus increased by 105%, and 10-day degradation rate decreased by 62%. Addition of BBG prevented the burst release of water from hydrogel dressings and enabled the continuous water release for up to 10 days, which is crucial in treating second-degree burn wounds. 3D-printed hydrogel dressings with BBG showed long-term cell viability that can be a result of the accumulative release of therapeutic ions from BBG particulate. The in vivo wound healing functionality of the dressings was investigated using a rat model with a second-degree burn wound. Our animal study showed that the 3D-printed dressings with BBG exhibited faster wound closure, non-adhesive contact, non-invasive debridement, and non-traumatic dressing removal. Histological analysis suggested that 3D-printed dressings contributed to more uniform re-epithelialization and tissue remodeling compared to the non-printed hydrogels of the same compositions. Critically, 3D-printed dressings with BBG led to significant regeneration of hair follicles compared to the 3D-printed hydrogel, non-printed hydrogel, and the control groups. The superior outcome of the 3D-printed hydrogel-BBG20 dressings can be attributed to the bioactive formulation, which promotes moist wound healing for longer time periods, and the non-adhesive porous texture of the 3D-printed dressings with increased wound-dressing interactions. Our findings provided proof of concept for the synergistic effect of bioactive formulation and the porous texture of the 3D-printed hydrogel dressings incorporated with BBG on continuous water release and, consequently, on second-degree burn wound healing.

Effect of Size and Concentration of Copper Nanoparticles on the Antimicrobial Activity in Escherichia coli through Multiple Mechanisms.

Metal and metal oxide nanoparticles, including copper nanoparticles (CuNPs), display antimicrobial activities and are regarded as promising microorganism inhibitors. Here, we explored the antimicrobial activity of CuNPs in Escherichia coli (E. coli) using two particle sizes (20 and 60 nm) and five concentrations (1, 5, 10, 50 and 100 µg/mL). The result showed a concentration-dependent trend of bactericidal activities for both size groups, with 20 nm particles more effective than 60 nm particles at low concentrations. The membrane disruption caused by CuNPs was confirmed by electron microscopy, PI staining and protein leaking analysis. However, the results of reactive oxygen species generation and genomic DNA damage revealed that the size and concentration of CuNPs were factors affecting the induction of multiple bactericidal mechanisms simultaneously on different scales. Further results of annexin V-PI staining supported this hypothesis by showing the shifting composition of the early-, late- and non-apoptotic dead cells across the CuNP groups. Many CuNP treatment groups were rescued when four mammalian modulators-wortmannin, necrosulfonamide, Z-VAD-FMK, and SBI-0206965-were applied separately. The results suggest the possible existence of bacterial programmed cell death pathways in E. coli which could be triggered by CuNP treatments.

A filter-based system mimicking the particle deposition and penetration in human respiratory system for secondhand smoke generation and characterization.

INTRODUCTION: Secondhand smoke endangers both the environment and the health of nonsmokers. Due to the scarcity of repeatable data generated by human subjects, a system capable of generating representative secondhand smoke is essential for studying smoke properties. This work presents the design and validation of a filter-based system that could mimic the particle deposition and penetration in human respiratory system for secondhand smoke generation and characterization. METHODS: Guided by our study on characterizing size-dependent filtration efficiency of common materials, we identified three filter media that generate similar particle deposition efficiencies compared to different regions of the human respiratory system over a wide submicron size range. We demonstrated the performance of the proposed filter-based system using various operating conditions. Additionally, we compared the properties of secondhand smoke particles to those of primary smoke particles. RESULTS: The difference in aerosol deposition efficiencies between the filter-based system and the International Commission on Radiological Protection (ICRP) model was less than 10% in the size range of 30 to 500 nm. High concentrations of metals were detected in the secondhand smoke. The contents of Ni and Cr generated from the secondhand electronic cigarettes are at least 20 and 5 times above the regulated daily maximum intake amount. CONCLUSION: Given the agreement in aerosol respiratory deposition between the filter-based system and the ICRP model, such a system can facilitate laboratory studies of secondhand smoke due to its simple structure, high repeatability, and ease of control while remaining free of human subjects.

Examining Metal Contents in Primary and Secondhand Aerosols Released by Electronic Cigarettes.

The usage of electronic cigarettes (ECs) has surged since their invention two decades ago. However, to date, the health effects of EC aerosol exposure are still not well understood because of insufficient data on the chemical composition of EC aerosols and the corresponding evidence of health risks upon exposure. Herein, we quantified the metals in primary and secondhand aerosols generated by three brands of ECs. By combining aerosol filter sampling and inductively coupled plasma mass spectrometry (ICP-MS), we assessed the mass of metals as a function of EC flavoring, nicotine concentration, device power, puff duration, and aging of the devices. The masses of Cr, Cu, Mn, Ni, Cu, and Zn were consistently high across all brands in the primary and secondhand aerosols, some of which were above the regulated maximum daily intake amount, especially for Cr and Ni with mass (nanograms per 10 puffs) emitted at 117 ± 54 and 50 ± 24 (JUUL), 125 ± 77 and 219 ± 203 (VOOPOO), and 33 ± 10 and 27 ± 2 (Vapor4Life). Our analysis indicates that the metals are predominantly released from the EC liquid, potentially through mechanisms such as bubble bursting or the vaporization of metal-organic compounds. High metal contents were also observed in simulated secondhand aerosols, generally 80-90% of those in primary aerosols. Our findings provide a more detailed understanding of the metal emission characteristics of EC for assessing its health effects and policymaking.

Bio-Membrane Internalization Mechanisms of Arginine-Rich Cell-Penetrating Peptides in Various Species.

Recently, membrane-active peptides or proteins that include antimicrobial peptides (AMPs), cytolytic proteins, and cell-penetrating peptides (CPPs) have attracted attention due to their potential applications in the biomedical field. Among them, CPPs have been regarded as a potent drug/molecules delivery system. Various cargoes, such as DNAs, RNAs, bioactive proteins/peptides, nanoparticles and drugs, can be carried by CPPs and delivered into cells in either covalent or noncovalent manners. Here, we focused on four arginine-rich CPPs and reviewed the mechanisms that these CPPs used for intracellular uptake across cellular plasma membranes. The varying transduction efficiencies of them alone or with cargoes were discussed, and the membrane permeability was also expounded for CPP/cargoes delivery in various species. Direct membrane translocation (penetration) and endocytosis are two principal mechanisms for arginine-rich CPPs mediated cargo delivery. Furthermore, the amino acid sequence is the primary key factor that determines the cellular internalization mechanism. Importantly, the non-cytotoxic nature and the wide applicability make CPPs a trending tool for cellular delivery.

MXene-Graphene Field-Effect Transistor Sensing of Influenza Virus and SARS-CoV-2.

An MXene-graphene field-effect transistor (FET) sensor for both influenza virus and 2019-nCoV sensing was developed and characterized. The developed sensor combines the high chemical sensitivity of MXene and the continuity of large-area high-quality graphene to form an ultra-sensitive virus-sensing transduction material (VSTM). Through polymer linking, we are able to utilize antibody-antigen binding to achieve electrochemical signal transduction when viruses are deposited onto the VSTM surface. The MXene-graphene VSTM was integrated into a microfluidic channel that can directly receive viruses in solution. The developed sensor was tested with various concentrations of antigens from two viruses: inactivated influenza A (H1N1) HA virus ranging from 125 to 250,000 copies/mL and a recombinant 2019-nCoV spike protein ranging from 1 fg/mL to 10 pg/mL. The average response time was about ∼50 ms, which is significantly faster than the existing real-time reverse transcription-polymerase chain reaction method (>3 h). The low limit of detection (125 copies/mL for the influenza virus and 1 fg/mL for the recombinant 2019-nCoV spike protein) has demonstrated the sensitivity of the MXene-graphene VSTM on the FET platform to virus sensing. Especially, the high signal-to-viral load ratio (∼10% change in source-drain current and gate voltage) also demonstrates the ultra-sensitivity of the developed MXene-graphene FET sensor. In addition, the specificity of the sensor was also demonstrated by depositing the inactivated influenza A (H1N1) HA virus and the recombinant 2019-nCoV spike protein onto microfluidic channels with opposite antibodies, producing signal differences that are about 10 times lower. Thus, we have successfully fabricated a relatively low-cost, ultrasensitive, fast-responding, and specific inactivated influenza A (H1N1) and 2019-nCoV sensor with the MXene-graphene VSTM.

Lactoferricin-Derived L5a Cell-Penetrating Peptide for Delivery of DNA into Cells.

Cell-penetrating peptides (CPPs) are small peptides which help intracellular delivery of functional macromolecules, including DNAs, RNAs, and proteins, across the cell membrane and into the cytosol, and even into the nucleus in some cases. Delivery of macromolecules can facilitate transfection, aid in gene therapy and transgenesis, and alter gene expression. L5a (RRWQW), originally derived from bovine lactoferricin, is one kind of CPPs which can promote cellular uptake of plasmid DNA and enters cells via direct membrane translocation. The peptide complexes noncovalently with DNA over a short incubation period. DNA plasmid and L5a complex stability is confirmed by a decrease in mobility in a gel retardation assay, and successful transfection is proven by the detection of a reporter gene in cells using fluorescent microscopy. Here, we describe methods to study noncovalent interactions between L5a and plasmid DNA, and the delivery of L5a/DNA complexes into cells. L5a is the one of the smallest CPPs discovered to date, providing a small delivery vehicle for macromolecules in mammalian cells. A small vehicle which can enter the nucleus is ideal for efficient gene uptake, transfer, and therapy. It is simple to complex with DNA plasmids, and its nature allows mammalian cells to be easily transfected.

Quantifying the effect of nano-TiO2 on the toxicity of lead on C. dubia using a two-compartment modeling approach.

Nanoparticles (NPs) can significantly influence toxicity imposed by toxic metals. However, this impact has not been quantified. In this research, we investigated the effect of nano-TiO2 on lead (Pb) accumulation and the resultant toxicity using water flea Ceriodaphnia dubia (C. dubia) as the testing organism. We used a two-compartment modeling approach, which included a two-compartment accumulation model and a toxicodynamic model, on the basis of Pb body tissue accumulation, to quantify the impact of nano-TiO2 on Pb toxicity. The effect of algae on the combined toxicity of Pb and nano-TiO2 was also quantified. The two-compartment accumulation model could well quantify Pb accumulation kinetics in two-compartments of C. dubia, the gut and the rest of the body tissue in the presence of nano-TiO2. Modeling results suggested that the gut quickly accumulates Pb through active uptake from the mouth, but the rest of the body tissue slowly accumulates Pb from the gut. The predicted Pb distribution within C. dubia was verified by depuration modeling results from an independent depuration test. The survivorship of C. dubia as a function of Pb accumulated in the body tissue and exposure time can be well described using a toxicodynamic model. The effects of algae on Pb accumulation in different compartments of C. dubia and the toxicity in the presence of nano-TiO2 were also well described using the two-compartment modeling approach. Therefore, the novel two-compartment modeling approach provides a useful tool for assessing the effect of NPs on aquatic ecosystems where toxic metals are present.

Evolutionary Timeline of Genetic Delivery and Gene Therapy.

There are more than 3,500 genes that are being linked to hereditary diseases or correlated with an elevated risk of certain illnesses. As an alternative to conventional treatments with small molecule drugs, gene therapy has arisen as an effective treatment with the potential to not just alleviate disease conditions but also cure them completely. In order for these treatment regimens to work, genes or editing tools intended to correct diseased genetic material must be efficiently delivered to target sites. There have been many techniques developed to achieve such a goal. In this article, we systematically review a variety of gene delivery and therapy methods that include physical methods, chemical and biochemical methods, viral methods, and genome editing. We discuss their historical discovery, mechanisms, advantages, limitations, safety, and perspectives.

Cell-Penetrating Peptides as a Potential Drug Delivery System for Effective Treatment of Diabetes.

BACKGROUND/PURPOSE: Type 2 diabetes (T2D) is characterized by hyperglycemia resulting from the body's inability to produce and/or use insulin. Patients with T2D often have hyperinsulinemia, dyslipidemia, inflammation, and oxidative stress, which then lead to hypertension, chronic kidney disease, cardiovascular disease, and increased risk of morbidity and mortality (9th leading cause globally). Insulin and related pharmacological therapies are widely used to manage T2D, despite their limitations. Efficient drug delivery systems (DDS) that control drug kinetics may decrease side effects, allow for efficient targeting, and increase the bioavailability of drugs to achieve maximum therapeutic benefits. Thus, the development of effective DDS is crucial to beat diabetes. METHODS: Here, we introduced a highly bioavailable vector, cell-penetrating peptides (CPPs), as a powerful DDS to overcome limitations of free drug administration. RESULTS: CPPs are short peptides that serve as a potent tool for delivering therapeutic agents across cell membranes. Various cargoes, including proteins, DNA, RNA, liposomes, therapeutic molecules, and nanomaterials, generally retain their bioactivity upon entering cells. The mechanisms of CPPs/cargoes intracellular entry are classified into two parts: endocytic pathways and direct membrane translocation. In this article, we focus on the applications of CPPs/therapeutic agents in the treatment of diabetes. Hypoglycemic drugs with CPPs intervention can enhance therapeutic effectiveness, and CPP-mediated drug delivery can facilitate the actions of insulin. Numerous studies indicate that CPPs can effectively deliver insulin, produce synergistic effects with immunosuppressants for successful pancreatic islet xenotransplantation, prolong pharmacokinetics, and retard diabetic nephropathy. CONCLUSION: We suggest that CPPs can be a new generation of drug delivery systems for effective treatment and management of diabetes and diabetes-associated complications.

Modeling the load of SARS-CoV-2 virus in human expelled particles during coughing and speaking.

Particle size is an essential factor when considering the fate and transport of virus-containing droplets expelled by human, because it determines the deposition pattern in the human respiratory system and the evolution of droplets by evaporation and gravitational settling. However, the evolution of virus-containing droplets and the size-dependent viral load have not been studied in detail. The lack of this information leads to uncertainties in understanding the airborne transmission of respiratory diseases, such as the COVID-19. In this study, through a set of differential equations describing the evolution of respiratory droplets and by using the SARS-CoV-2 virus as an example, we investigated the distribution of airborne virus in human expelled particles from coughing and speaking. More specifically, by calculating the vertical distances traveled by the respiratory droplets, we examined the number of viruses that can remain airborne and the size of particles carrying these airborne viruses after different elapsed times. From a single cough, a person with a high viral load in respiratory fluid (2.35 × 109 copies per ml) may generate as many as 1.23 × 105 copies of viruses that can remain airborne after 10 seconds, compared to 386 copies of a normal patient (7.00 × 106 copies per ml). Masking, however, can effectively block around 94% of the viruses that may otherwise remain airborne after 10 seconds. Our study found that no clear size boundary exists between particles that can settle and can remain airborne. The results from this study challenge the conventional understanding of disease transmission routes through airborne and droplet mechanisms. We suggest that a complete understanding of the respiratory droplet evolution is essential and needed to identify the transmission mechanisms of respiratory diseases.

3D-printed Biomimetic Bioactive Glass Scaffolds for Bone Regeneration in Rat Calvarial Defects.

The pore geometry of scaffold intended for the use in the bone repair or replacement is one of the most important parameters in bone tissue engineering. It affects not only the mechanical properties of the scaffold but also the amount of bone regeneration after implantation. Scaffolds with five different architectures (cubic, spherical, x, gyroid, and diamond) at different porosities were fabricated with bioactive borate glass using the selective laser sintering (SLS) process. The compressive strength of scaffolds with porosities ranging from 60% to 30% varied from 1.7 to 15.5 MPa. The scaffold's compressive strength decreased significantly (up to 90%) after 1-week immersion in simulated body fluids. Degradation of scaffolds is dependent on porosity, in which the scaffold with the largest surface area has the largest reduction in strength. Scaffolds with traditional cubic architecture and biomimetic diamond architecture were implanted in 4.6 mm diameter full-thickness rat calvarial defects for 6 weeks to evaluate the bone regeneration with or without bone morphogenetic protein 2 (BMP-2). Histological analysis indicated no significant difference in bone formation in the defects treated with the two different architectures. However, the defects treated with the diamond architecture scaffolds had more fibrous tissue formation and thus have the potential for faster bone formation. Overall, the results indicated that borate glass scaffolds fabricated using the SLS process have the potential for bone repair and the addition of BMP-2 significantly improves bone regeneration.

Cytotoxicity of NiO and Ni(OH)2 Nanoparticles Is Mediated by Oxidative Stress-Induced Cell Death and Suppression of Cell Proliferation.

The use of nanomaterial-based products continues to grow with advancing technology. Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that products containing them do not impose harmful effects to human or environmental health. In this study, we evaluated the comparative cytotoxicity between nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) in human bronchoalveolar carcinoma (A549) and human hepatocellular carcinoma (HepG2) cell lines. Cellular viability studies revealed cell line-specific cytotoxicity in which nickel NPs were toxic to A549 cells but relatively nontoxic to HepG2 cells. Time-, concentration-, and particle-specific cytotoxicity was observed in A549 cells. NP-induced oxidative stress triggered dissipation of mitochondrial membrane potential and induction of caspase-3 enzyme activity. The subsequent apoptotic events led to reduction in cell number. In addition to cell death, suppression of cell proliferation played an essential role in regulating cell number. Collectively, the observed cell viability is a function of cell death and suppression of proliferation. Physical and chemical properties of NPs such as total surface area and metal dissolution are in agreement with the observed differential cytotoxicity. Understanding the properties of NPs is essential in informing the design of safer materials.

Differential Cytotoxicity Induced by Transition Metal Oxide Nanoparticles is a Function of Cell Killing and Suppression of Cell Proliferation.

The application of nanoparticles (NPs) in industry is on the rise, along with the potential for human exposure. While the toxicity of microscale equivalents has been studied, nanoscale materials exhibit different properties and bodily uptake, which limits the prediction ability of microscale models. Here, we examine the cytotoxicity of seven transition metal oxide NPs in the fourth period of the periodic table of the chemical elements. We hypothesized that NP-mediated cytotoxicity is a function of cell killing and suppression of cell proliferation. To test our hypothesis, transition metal oxide NPs were tested in a human lung cancer cell model (A549). Cells were exposed to a series of concentrations of TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, or ZnO for either 24 or 48 h. All NPs aside from Cr2O3 and Fe2O3 showed a time- and dose-dependent decrease in viability. All NPs significantly inhibited cellular proliferation. The trend of cytotoxicity was in parallel with that of proliferative inhibition. Toxicity was ranked according to severity of cellular responses, revealing a strong correlation between viability, proliferation, and apoptosis. Cell cycle alteration was observed in the most toxic NPs, which may have contributed to promoting apoptosis and suppressing cell division rate. Collectively, our data support the hypothesis that cell killing and cell proliferative inhibition are essential independent variables in NP-mediated cytotoxicity.

Relaxin enhances bone regeneration with BMP-2-loaded hydroxyapatite microspheres.

Our aims were to 1) evaluate the capacity of hollow hydroxyapatite (HA) microspheres (212-250 µm) to serve as a delivery system for controlled release of BMP-2 in vitro and 2) examine relaxin as an enhancer of BMP-2 for bone regeneration. Hollow HA microspheres were converted from borate glass microspheres and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, and the Brunauer-Emmett-Teller method. The microspheres loaded with BMP-2 and relaxin were implanted for 6 weeks in Sprague Dawley rats with calvarial defects. BMP-2 alone in the range up to 1 µg per defect exhibited dose-dependent bone regeneration while relaxin alone in the range up to 0.25 µg per defect did not promote bone regeneration. When compared with BMP-2 alone (1 µg per defect), a 50% reduction in the BMP-2 dose was achieved with the addition of 0.05, 0.1, or 0.25 µg of relaxin per defect. These results show that loading HA microspheres with a combination of relaxin and BMP-2 can significantly reduce the BMP-2 dose required to regenerate an equivalent amount of bone.

Polyhistidine facilitates direct membrane translocation of cell-penetrating peptides into cells.

The bovine lactoferricin L6 (RRWQWR) has been previously identified as a novel cell-penetrating peptide (CPP) that is able to efficiently internalize into human cells. L6 interacts with quantum dots (QDs) noncovalently to generate stable L6/QD complexes that enter cells by endocytosis. In this study, we demonstrate a modified L6 (HL6; CHHHHHRRWQWRHHHHHC), in which short polyhistidine peptides are introduced into both flanks of L6, has enhanced cell-penetrating ability in human bronchoalveolar carcinoma A549 cells. The mechanism of cellular uptake of HL6/QD complexes is primarily direct membrane translocation rather than endocytosis. Dimethyl sulfoxide (DMSO), but not pyrenebutyrate (PB), ethanol, oleic acid, or 1,2-benzisothiazol-3(2 H)-one (BIT), slightly enhances HL6-mediated protein transduction efficiency. Neither HL6 nor HL6/QD complexes are cytotoxic to A549 or HeLa cells. These results indicate that HL6 could be a more efficient drug carrier than L6 for biomedical as well as biotechnological applications, and that the function of polyhistidine peptides is critical to CPP-mediated protein transduction.

Algae (Raphidocelis) reduce combined toxicity of nano-TiO2 and lead on C. dubia.

Nanoparticles (NPs) often serve as carriers of background toxins and enhance their toxicity on aquatic organisms such as Ceriodaphnia dubia (C. dubia). However, foods, especially algae, are also present in natural water and impacts this type of toxicity. This study investigated the effect of algae on the combined toxicity of nano-TiO2 and lead (Pb). A mixture of yeast-trout chow-cereal leaves (YTC) was also used as another model food. Results indicated that, both algae and YTC significantly reduce the combined toxicity of nano-TiO2 and Pb. Further investigation indicated that the ingestion of algae had minimal impacts on Pb uptake by, Pb depuration from, and Pb distribution within the C. dubia. Therefore, the toxicity reduction from algae ingestion should come from mechanisms other than the change in Pb mass and speciation in C. dubia, which will need future investigation. Nevertheless, the effect of food on the mitigation of combined toxicity of NPs and heavy metals must be considered when assessing the toxicity of nanoparticles in the natural environment because food always exists in natural waterbodies where aquatic organisms grow.

Intracellular Delivery of Nanoparticles Mediated by Lactoferricin Cell-Penetrating Peptides in an Endocytic Pathway.

Cell-penetrating peptides (CPPs) containing a preponderance of basic amino acids are able to deliver biologically active macromolecules and nanomaterials into live cells. Quantum dots (QDs) are nanoparticles with unique fluorescence properties that have found wide application in biomedical imaging. In this study, we demonstrate transduction of an L6 CPP (RRWQWR) derived from bovine lactoferricin (LFcin) into human lung cancer cells. L6 noncovalently interacts with QDs to form stable complexes. L6/QD complexes enter cells most efficiently when prepared at a nitrogen/phosphate ratio of 60. Mechanistic studies indicate that L6/QD complexes enter cells by endocytosis. Treatment with 1,2-benzisothiazol-3(2H)-one (BIT), an industrial preservative that enhances uptake of certain CPPs, does not affect L6 CPP-mediated protein transduction efficiency. L6 and L6/QD complexes are not cytotoxic. These results indicate that L6 LFcin might be an efficient and safe nanoshuttle for nanoparticles or nanomedicines in biomedical applications.