Stimuli-Responsive Adaptive Nanotoxin to Directly Penetrate the Cellular Membrane by Molecular Folding and Unfolding.

Biological nanomachines, including proteins and nucleic acids whose function is activated by conformational changes, are involved in every biological process, in which their dynamic and responsive behaviors are controlled by supramolecular recognition. The development of artificial nanomachines that mimic the biological functions for potential application as therapeutics is emerging; however, it is still limited to the lower hierarchical level of the molecular components. In this work, we report a synthetic machinery nanostructure in which actuatable molecular components are integrated into a hierarchical nanomaterial in response to external stimuli to regulate biological functions. Two nanometers core-sized gold nanoparticles are covered with ligand layers as actuatable components, whose folding/unfolding motional response to the cellular environment enables the direct penetration of the nanoparticles across the cellular membrane to disrupt intracellular organelles. Furthermore, the pH-responsive conformational movements of the molecular components can induce the apoptosis of cancer cells. This strategy based on the mechanical motion of molecular components on a hierarchical nanocluster would be useful to design biomimetic nanotoxins.

Structural equation modeling of work-related conditions on safety perception and safety education in waste and recycling collectors.

Waste and recycling collectors are responsible for cleaning, collecting, transporting and sorting various garbage. The purpose of this study is to investigate relationships between work-related conditions, safety perception and safety education in waste and recycling collectors. A total of 675 workers who collect domestic, street, recyclable or food waste were selected by stratified sampling in the waste and recycling industry. A structural equation model was used to analyze whether work-related conditions and safety perception affect safety education factors and whether there exists a causal relationship between them. According to the results of structural equation modeling, work-related conditions directly affect the level of safety education and indirectly affect the level of safety education by having an impact on safety perception. Waste and recycling collectors are more likely to participate in safety education and to be more concerned about safety education as company size and salaries increase. The results of this study suggest that accident-prevention measures that are appropriate to job characteristics are effective because worker's features and their safety climate are different according to job type in the service industry.

Enhanced Isolation and Release of Circulating Tumor Cells Using Nanoparticle Binding and Ligand Exchange in a Microfluidic Chip.

The detection of rare circulating tumor cells (CTCs) in the blood of cancer patients has the potential to be a powerful and noninvasive method for examining metastasis, evaluating prognosis, assessing tumor sensitivity to drugs, and monitoring therapeutic outcomes. In this study, we have developed an efficient strategy to isolate CTCs from the blood of breast cancer patients using a microfluidic immune-affinity approach. Additionally, to gain further access to these rare cells for downstream characterization, our strategy allows for easy detachment of the captured CTCs from the substrate without compromising cell viability or the ability to employ next generation RNA sequencing for the identification of specific breast cancer genes. To achieve this, a chemical ligand-exchange reaction was engineered to release cells attached to a gold nanoparticle coating bound to the surface of a herringbone microfluidic chip (NP-HBCTC-Chip). Compared to the use of the unmodified HBCTC-Chip, our approach provides several advantages, including enhanced capture efficiency and recovery of isolated CTCs.

Multimonth controlled small molecule release from biodegradable thin films.

Long-term, localized delivery of small molecules from a biodegradable thin film is challenging owing to their low molecular weight and poor charge density. Accomplishing highly extended controlled release can facilitate high therapeutic levels in specific regions of the body while significantly reducing the toxicity to vital organs typically caused by systemic administration and decreasing the need for medical intervention because of its long-lasting release. Also important is the ability to achieve high drug loadings in thin film coatings to allow incorporation of significant drug amounts on implant surfaces. Here we report a sustained release formulation for small molecules based on a soluble charged polymer-drug conjugate that is immobilized into nanoscale, conformal, layer-by-layer assembled films applicable to a variety of substrate surfaces. We measured a highly predictable sustained drug release from a polymer thin film coating of 0.5-2.7 µm that continued for more than 14 mo with physiologically relevant drug concentrations, providing an important drug delivery advance. We demonstrated this effect with a potent small molecule nonsteroidal anti-inflammatory drug, diclofenac, because this drug can be used to address chronic pain, osteoarthritis, and a range of other critical medical issues.

Regulating exocytosis of nanoparticles via host-guest chemistry.

Prolonged retention of internalized nanoparticulate systems inside cells improves their efficacy in imaging, drug delivery, and theranostic applications. Especially, regulating exocytosis of the nanoparticles is a key factor in the fabrication of effective nanocarriers for chemotherapeutic treatments but orthogonal control of exocytosis in the cellular environment is a major challenge. Herein, we present the first example of regulating exocytosis of gold nanoparticles (AuNPs), a model drug carrier, by using a simple host-guest supramolecular system. AuNPs featuring quaternary amine head groups were internalized into the cells through endocytosis. Subsequent in situ treatment of a complementary cucurbit[7]uril (CB[7]) to the amine head groups resulted in the AuNP-CB[7] complexation inside cells, rendering particle assembly. This complexation induced larger particle assemblies that remained sequestered in the endosomes, inhibiting exocytosis of the particles without any observed cytotoxicity.

Advancing Cancer Treatment: Enhanced Combination Therapy through Functionalized Porous Nanoparticles.

Cancer remains a major global health challenge, necessitating the development of innovative treatment strategies. This review focuses on the functionalization of porous nanoparticles for combination therapy, a promising approach to enhance cancer treatment efficacy while mitigating the limitations associated with conventional methods. Combination therapy, integrating multiple treatment modalities such as chemotherapy, phototherapy, immunotherapy, and others, has emerged as an effective strategy to address the shortcomings of individual treatments. The unique properties of mesoporous silica nanoparticles (MSN) and other porous materials, like nanoparticles coated with mesoporous silica (NP@MS), metal-organic frameworks (MOF), mesoporous platinum nanoparticles (mesoPt), and carbon dots (CDs), are being explored for drug solubility, bioavailability, targeted delivery, and controlled drug release. Recent advancements in the functionalization of mesoporous nanoparticles with ligands, biomaterials, and polymers are reviewed here, highlighting their role in enhancing the efficacy of combination therapy. Various research has demonstrated the effectiveness of these nanoparticles in co-delivering drugs and photosensitizers, achieving targeted delivery, and responding to multiple stimuli for controlled drug release. This review introduces the synthesis and functionalization methods of these porous nanoparticles, along with their applications in combination therapy.

Role of Functionalized Peptides in Nanomedicine for Effective Cancer Therapy.

Peptide-functionalized nanomedicine, which addresses the challenges of specificity and efficacy in drug delivery, is emerging as a pivotal approach for cancer therapy. Globally, cancer remains a leading cause of mortality, and conventional treatments, such as chemotherapy, often lack precision and cause adverse effects. The integration of peptides into nanomedicine offers a promising solution for enhancing the targeting and delivery of therapeutic agents. This review focuses on the three primary applications of peptides: cancer cell-targeting ligands, building blocks for self-assembling nanostructures, and elements of stimuli-responsive systems. Nanoparticles modified with peptides improved targeting of cancer cells, minimized damage to healthy tissues, and optimized drug delivery. The versatility of self-assembled peptide structures makes them an innovative vehicle for drug delivery by leveraging their biocompatibility and diverse nanoarchitectures. In particular, the mechanism of cell death induced by self-assembled structures offers a novel approach to cancer therapy. In addition, peptides in stimuli-responsive systems enable precise drug release in response to specific conditions in the tumor microenvironment. The use of peptides in nanomedicine not only augments the efficacy and safety of cancer treatments but also suggests new research directions. In this review, we introduce systems and functionalization methods using peptides or peptide-modified nanoparticles to overcome challenges in the treatment of specific cancers, including breast cancer, lung cancer, colon cancer, prostate cancer, pancreatic cancer, liver cancer, skin cancer, glioma, osteosarcoma, and cervical cancer.

Microbubble Delivery Platform for Ultrasound-Mediated Therapy in Brain Cancers.

The blood-brain barrier (BBB) is one of the most selective endothelial barriers that protect the brain and maintains homeostasis in neural microenvironments. This barrier restricts the passage of molecules into the brain, except for gaseous or extremely small hydrophobic molecules. Thus, the BBB hinders the delivery of drugs with large molecular weights for the treatment of brain cancers. Various methods have been used to deliver drugs to the brain by circumventing the BBB; however, they have limitations such as drug diversity and low delivery efficiency. To overcome this challenge, microbubbles (MBs)-based drug delivery systems have garnered a lot of interest in recent years. MBs are widely used as contrast agents and are recently being researched as a vehicle for delivering drugs, proteins, and gene complexes. The MBs are 1-10 µm in size and consist of a gas core and an organic shell, which cause physical changes, such as bubble expansion, contraction, vibration, and collapse, in response to ultrasound. The physical changes in the MBs and the resulting energy lead to biological changes in the BBB and cause the drug to penetrate it, thus enhancing the therapeutic effect. Particularly, this review describes a state-of-the-art strategy for fabricating MB-based delivery platforms and their use with ultrasound in brain cancer therapy.

Light-Responsive Layer-By-Layer Film Containing Gold Nanorods for Sequential Drug Release.

Chemically and physically stable multidrug-loaded layer-by-layer (LbL) films are promising candidates for sequential and on-demand drug release at concentrations suitable for various applications. The synergistic effect of the sequential release of drugs may enhance their therapeutic efficacy in treating skin cancer and other complex medical conditions. In this study, we prepared LbL films by alternating the deposition of cationic linear polyethylenimine, camptothecin (CPT)-loaded gold nanorods (GNRs), anionic poly(styrenesulfonate), and doxorubicin (DOX) based on electrostatic interactions. The film exhibited loading of CPT and DOX, which could be tuned according to the requirements of the application by changing the parameters of the LbL process. Herein, CPT was encapsulated in GNRs and showed good stability and absorption in the near-infrared (NIR) range (650-900 nm). The prepared LbL film showed a pH-dependent DOX release. Subsequently, the functionalized GNRs showed excellent photothermal properties, which assisted the on-demand release of CPT upon NIR irradiation with further release of DOX. Our results suggest that the LbL approach for sequential drug release can be an effective drug delivery platform owing to its cytocompatibility, anticancer effects, and stimuli-responsive properties.

Smart Delivery Platform Using Core-Shell Nanofibers for Sequential Drug Release in Wound Healing.

An effective approach to accelerating wound healing is through a smart delivery platform that releases drugs according to the needs of different healing periods. With the growing demand for wound care and treatment, electrospun nanofibers have attracted considerable attention owing to their simple and versatile method of manufacturing, unique structure, and biological functions similar to those of the extracellular matrix. Moreover, nanofibers can be loaded with active substances that promote targeted wound healing. In this study, we investigated the performance of a core-shell nanofiber platform loaded with two drugs in the core and shell, respectively. The shell polymer, poly-l-lactic acid, initially releases the encapsulated drug into an aqueous solution at room temperature. Gold nanorods with near-infrared absorbance were incorporated in the core polymer poly(N-isopropylacrylamide) to produce localized heat by plasmon resonance when exposed to light. This allows the thermally responsive core polymer to swell and shrink for programmable drug release. Our study provides a versatile platform for controlled and safe drug delivery to wound sites and could be applied to the treatment of other topical diseases.

Using flow to switch the valency of bacterial capture on engineered surfaces containing immobilized nanoparticles.

Toward an understanding of nanoparticle-bacterial interactions and the development of sensors and other substrates for controlled bacterial adhesion, this article describes the influence of flow on the initial stages of bacterial capture (Staphylococcus aureus) on surfaces containing cationic nanoparticles. A PEG (poly(ethylene glycol)) brush on the surface around the nanoparticles sterically repels the bacteria. Variations in ionic strength tune the Debye length from 1 to 4 nm, increasing the strength and range of the nanoparticle attractions toward the bacteria. At relatively high ionic strengths (physiological conditions), bacterial capture requires several nanoparticle-bacterial contacts, termed "multivalent capture". At low ionic strength and gentle wall shear rates (on the order of 10 s(-1)), individual bacteria can be captured and held by single surface-immobilized nanoparticles. Increasing the flow rate to 50 s(-1) causes a shift from monovalent to divalent capture. A comparison of experimental capture efficiencies with statistically determined capture probabilities reveals the initial area of bacteria-surface interaction, here about 50 nm in diameter for a Debye length κ(-1) of 4 nm. Additionally, for κ(-1) = 4 nm, the net per nanoparticle binding energies are strong but highly shear-sensitive, as is the case for biological ligand-receptor interactions. Although these results have been obtained for a specific system, they represent a regime of behavior that could be achieved with different bacteria and different materials, presenting an opportunity for further tuning of selective interactions. These finding suggest the use of surface elements to manipulate individual bacteria and nonfouling designs with precise but finite bacterial interactions.

Effects of Nanobubbles in Dermal Delivery of Drugs and Cosmetics.

Dermal delivery, which delivers drugs and cosmetics through the skin, has attracted significant attention due to its non-invasive and simple administration compared with oral or injectable administration. However, delivery of the ingredients through the skin barrier is difficult because the primary function of the skin is to protect the human body by preventing the invasion of contaminants. Although various techniques have been developed to overcome skin barriers, chemical toxicity, complicated processes, and expensive equipment still remain as obstacles. Moreover, green chemistry, which minimizes or eliminates the use of toxic chemicals, is required in the cosmetic industry. Thus, the development of a new method for dermal delivery is required. In this study, we provide a new method for dermal delivery using nanobubbles (NBs). NBs generated in oil improve the delivery effect of the active ingredients through the high Brownian motion and charge-balancing effect. Franz cell experiments and depigmentation experiments using the B16F10 melanoma cells were conducted to confirm the enhanced delivery effects. The system using NBs will contribute to the advancement of the dermal delivery of drugs and cosmetics.

On-Demand Drug Delivery Systems Using Nanofibers.

On-demand drug-delivery systems using nanofibers are extensively applicable for customized drug release based on target location and timing to achieve the desired therapeutic effects. A nanofiber formulation is typically created for a certain medication and changing the drug may have a significant impact on the release kinetics from the same delivery system. Nanofibers have several distinguishing features and properties, including the ease with which they may be manufactured, the variety of materials appropriate for processing into fibers, a large surface area, and a complex pore structure. Nanofibers with effective drug-loading capabilities, controllable release, and high stability have gained the interest of researchers owing to their potential applications in on-demand drug delivery systems. Based on their composition and drug-release characteristics, we review the numerous types of nanofibers from the most recent accessible studies. Nanofibers are classified based on their mechanism of drug release, as well as their structure and content. To achieve controlled drug release, a suitable polymer, large surface-to-volume ratio, and high porosity of the nanofiber mesh are necessary. The properties of nanofibers for modified drug release are categorized here as protracted, stimulus-activated, and biphasic. Swellable or degradable polymers are commonly utilized to alter drug release. In addition to the polymer used, the process and ambient conditions can have considerable impacts on the release characteristics of the nanofibers. The formulation of nanofibers is highly complicated and depends on many variables; nevertheless, numerous options are available to accomplish the desired nanofiber drug-release characteristics.

Stimuli-Responsive Nanofibers Containing Gold Nanorods for On-Demand Drug Delivery Platforms.

On-demand drug delivery systems using nanofibers have attracted significant attention owing to their controllable properties for drug release through external stimuli. Near-infrared (NIR)-responsive nanofibers provide a platform where the drug release profile can be achieved by the on-demand supply of drugs at a desired dose for cancer therapy. Nanomaterials such as gold nanorods (GNRs) exhibit absorbance in the NIR range, and in response to NIR irradiation, they generate heat as a result of a plasmon resonance effect. In this study, we designed poly (N-isopropylacrylamide) (PNIPAM) composite nanofibers containing GNRs. PNIPAM is a heat-reactive polymer that provides a swelling and deswelling property to the nanofibers. Electrospun nanofibers have a large surface-area-to-volume ratio, which is used to effectively deliver large quantities of drugs. In this platform, both hydrophilic and hydrophobic drugs can be introduced and manipulated. On-demand drug delivery systems were obtained through stimuli-responsive nanofibers containing GNRs and PNIPAM. Upon NIR irradiation, the heat generated by the GNRs ensures shrinking of the nanofibers owing to the thermal response of PNIPAM, thereby resulting in a controlled drug release. The versatility of the light-responsive nanofibers as a drug delivery platform was confirmed in cell studies, indicating the advantages of the swelling and deswelling property of the nanofibers and on-off drug release behavior with good biocompatibility. In addition, the system has potential for the combination of chemotherapy with multiple drugs to enhance the effectiveness of complex cancer treatments.

Analysis of occupational injuries and the risk management of automobile parts manufacturing work.

Background. Unexpected occupational injuries frequently occur in the automobile parts manufacturing industry. This study investigates the characteristics of occupational injuries and risk management for the workers in the industry. Methods. From the national industrial accident compensation data in Korea, 1530 occupational injuries were analyzed by nature and source of injury and illness according to work process. Also, this study derived the risk management level for prioritizing preventative measures. Results. The most critical injuries were 'ACC (amputation or caught in or crushed or compressed)' caused by 'misoperation or malfunction of machine and equipment' in the 'fabrication' and the 'maintenance' processes. Possible incidents predicted as a 'high' level of risk management were 'struck' (struck by or against objects) caused by 'misoperation or malfunction of machine and equipment' and ACC during 'installation of jig and mold' in the 'fabrication' process. ACC during 'maintenance' of 'operating jig and mold' is also classified 'high'. Discussion and conclusion. Using the findings of this study, effective preventative measures to reduce occupational injuries according to the risk level are suggested and discussed for automobile parts manufacturing works.

Risk assessment of educational support staff's work in schools.

BACKGROUND: Educational support staff (educational staff) in schools perform widely distinctive activities according to their occupation and work process. OBJECTIVE: This study analyzes the possible incidents for each occupation and work process, and suggests a risk matrix prioritizing the risks of educational staff's work. METHODS: A total of 1,566 injuries of educational staff, registered for occupational injuries and illnesses between 2015 and 2016, were used to develop the risk matrix considering injuries, sick leave days, and disabilities. RESULTS: Among the 1,566 injuries, 'Cook-cooking/serving: Burn' (8.5%) was the most frequent incident. 'Cook-manual materials handling (MMH): musculoskeletal disorders (MSDs)' (241.6 sick leave days) was the most severe incident, and the number of disabilities was high in the forms of 'Cook-cooking/serving: MSDs.' According to risk assessment results, possible incidents predicted as 'High' level of risk management were in the forms of 'Cook-cooking/serving: MSDs,' 'Cook-MMH: Slip and trip,' 'Cook-cleaning/repairing: Fall from a height,' 'Cook-walking: Slip and trip,' 'Cook-MMH: MSDs,' 'Cook-cooking/serving: Burn,' 'Cook-cleaning/repairing: Slip and trip,' 'Custodian-cleaning/repairing: Fall from a height,' and 'Instructor-walking: Slip and trip.' CONCLUSIONS: The results can be used to develop an effective injury prevention policy, and to allocate resources for risk management in ensuring school safety.

Development of Gold Nanoparticle Micropatterns for the Electrical Detection of Proteins.

Protein analysis can be used to efficiently detect the early stages of various diseases. However, conventional protein detection platforms require expensive or complex equipment, which has been a major obstacle to their widespread application. In addition, uncertain signals from non-specific adhesion interfere with the precise interpretation of the results. To overcome these problems, the development of a technique that can detect the proteins in a simple method is needed. In this study, a platform composed of gold nanoparticles (GNPs) was fabricated through a simple imprinting method for protein detection. The corrugated surface naturally formed by the nanoparticle assemblies simultaneously increases the efficiency of adhesion and binding with analytes and reduces undesired interactions. After forming the GNP micropatterns, post-functionalization with both cationic and neutral ligands was performed on the surface to manipulate their electrostatic interaction with proteins. Upon protein binding, the change in the electrical values of the micropatterns was recorded by using a resistance meter. The resistance of the positively charged micropatterns was found to increase due to the electrostatic interaction with proteins, while no significant change in resistance was observed for the neutral micropatterns after immersion in a protein solution. Additionally, the selective adsorption of fluorescent proteins onto the micropatterns was captured using confocal microscopy. These simply imprinted GNP micropatterns are sensitive platforms that can detect various analytes by measuring the electrical resistance with portable equipment.

Drug resistance-free cytotoxic nanodrugs in composites for cancer therapy.

Drug resistance is a major cause of treatment failure for small-molecule cancer chemotherapies, despite the advances in combination therapies, drug delivery systems, epigenetic drugs, and proteolysis-targeting chimeras. Herein, we report the use of a drug resistance-free cytotoxic nanodrug as an alternative to small-molecule drugs. The present nanodrugs comprise 2 nm core gold nanoparticles (AuNPs) covered completely with multivalent hydrocarbon chains to a final diameter of ∼10 nm as single drug molecules. This hydrophobic drug-platform was delivered in composite form (∼35 nm) with block-copolymer like other small-molecular drugs. Upon uptake by cells, the nanodrugs enhanced the intracellular levels of reactive oxygen species and induced apoptosis, presumably reflecting multivalent interactions between aliphatic chains and intracellular biomolecules. No resistance to our novel nanodrug was observed following multiple treatment passages and the potential for use in cancer therapy was verified in a breast cancer patient-derived xenograft mouse model. These findings provide insight into the use of nano-scaled compounds as agents that evade drug resistance to cancer therapy.

Comparison of work-related traffic crashes between male taxi drivers aged ≥65 years and <65 years in South Korea.

BACKGROUND: The percentage of drivers aged ≥65 years among all Korean taxi drivers has risen sharply from 3.2% in 2006 to 22.0% in 2016. OBJECTIVE: This study compared the characteristics of work-related traffic crashes between male taxi drivers aged ≥65 years and <65 years. METHODS: Using the national compensation data of South Korea, 586 injured male taxi drivers were analyzed based on driver-related (work experience, company size, employment status, injured body part, and injury type) and crash-related factors (time and day of the crash, weather condition, road type, violation and drowsiness) by age group. RESULTS: For the injured drivers aged ≥65, percentages of the crashes related to some factors were lower than those of the drivers aged <65 years: at night (55.2% vs. 64.0%), on rainy or snowy day (7.8% vs. 21.3%), on straight road (40.5% vs 50.9%) and on the expressway (6.9% vs. 13.0%). However, the percentage of the crashes related to a violation for the injured drivers aged ≥65 years (23.3%) was higher than that of the drivers aged <65 years (13.4%). Furthermore, the taxi drivers aged ≥65 years had a higher death rate (14.7%) than the drivers aged <65 years (8.5%). CONCLUSIONS: The results can be useful for injury prevention policies and guidelines for elderly taxi drivers such as strengthened qualification tests for the aged drivers and improvement of the working environment.

Effects of age and violations on occupational accidents among motorcyclists performing food delivery.

BACKGROUND: Risk factors for motorcycle injuries are associated with rider-related factors and crash-related factors. OBJECTIVE: This study investigates the effects of age and violations on occupational accidents among motorcyclists performing food delivery. METHODS: This study analyzed 1,317 injured couriers regarding rider-related factors and crash-related factors according to rider's age or violations. RESULTS: Among injured riders, 67.4% were temporary workers, 76.1% worked in small companies with <5 employees, 58.7% in the nighttime, and 51.5% had a work experience of <1 month. However, among the injured teens, 93.5% were temporary workers, 87.0% in companies with <5 employees, 79.5% in nighttime, and 61.4% with work experience of <1 month. The proportion of novice with <1 month, of the temporary worker, of 'head/face/neck' injury, or of the 'concussion/hemorrhage' type of injury all decreased with age. However, the proportion of 'fracture,' 'rider alone,' or 'death or disability' accidents increased with age. Furthermore, the violation rate was high in teens (17.4%), at night (15.4%), or in type of 'crash with a car' (26.2%). The violation rate decreased with age. CONCLUSIONS: The results are expected to be useful for injury prevention policies and guidelines in the food delivery industries.