The Induction of Combined Hyperthermal Ablation Effect of Irreversible Electroporation with Polydopamine Nanoparticle-Coated Electrodes.

Irreversible electroporation (IRE) is a prominent non-thermal ablation method widely employed in clinical settings for the focal ablation therapy of solid tumors. Utilizing high-voltage, short-duration electric pulses, IRE induces perforation defects in the cell membrane, leading to apoptotic cell death. Despite the promise of irreversible electroporation (IRE) in clinical applications, it faces challenges concerning the coverage of target tissues for ablation, particularly when compared to other thermal ablation therapies such as radiofrequency ablation, microwave ablation, and cryoablation. This study aims to investigate the induced hyperthermal effect of IRE by applying a polydopamine nanoparticle (Dopa NP) coating on the electrode. We hypothesize that the induced hyperthermal effect enhances the therapeutic efficacy of IRE for cancer ablation. First, we observed the hyperthermal effect of IRE using Dopa NP-coated electrodes in hydrogel phantom models and then moved to in vivo models. In particular, in in vivo animal studies, the IRE treatment of rabbit hepatic lobes with Dopa NP-coated electrodes exhibited a two-fold higher increase in temperature (ΔT) compared to non-coated electrodes. Through a comprehensive analysis, we found that IRE treatment with Dopa NP-coated electrodes displayed the typical histological signatures of hyperthermal ablation, including the disruption of the hepatic cord and lobular structure, as well as the infiltration of erythrocytes. These findings unequivocally highlight the combined efficacy of IRE with Dopa NPs for electroporation and the hyperthermal ablation of target cancer tissues.

Optimizing protein delivery rate from silk fibroin hydrogel using silk fibroin-mimetic peptides conjugation.

Controlled release of proteins, such as growth factors, from biocompatible silk fibroin (SF) hydrogel is valuable for its use in tissue engineering, drug delivery, and other biological systems. To achieve this, we introduced silk fibroin-mimetic peptides (SFMPs) with the repeating unit (GAGAGS)n. Using green fluorescent protein (GFP) as a model protein, our results showed that SFMPs did not affect the GFP function when conjugated to it. The SFMP-GFP conjugates incorporated into SF hydrogel did not change the gelation time and allowed for controlled release of the GFP. By varying the length of SFMPs, we were able to modulate the release rate, with longer SFMPs resulting in a slower release, both in water at room temperature and PBS at 37 °C. Furthermore, the SF hydrogel with the SFMPs showed greater strength and stiffness. The increased ß-sheet fraction of the SF hydrogel, as revealed by FTIR analysis, explained the gel properties and protein release behavior. Our results suggest that the SFMPs effectively control protein release from SF hydrogel, with the potential to enhance its mechanical stability. The ability to modulate release rates by varying the SFMP length will benefit personalized and controlled protein delivery in various systems.

Assessment of Hepatic Lesions After non-Thermal Tumor Ablation by Irreversible Electroporation in a Pig Model.

Irreversible electroporation (IRE) is a non-thermal and minimal invasive modality to ablate pathologic lesions such as hepatic tumors. Histological analysis of the initial lesions after IRE can help predict ablation efficacy. We aimed to investigate the histological characteristics of early hepatic lesions after IRE application using animal models. IRE (1500 V/cm, a pulse length of 100 µs, 60 or 90 pulses) was applied to the liver of miniature pigs. H&E and TUNEL staining were performed and analyzed. Ablated zones of pig liver were discolored and separated from the normal zone after IRE. Histologic characteristics of ablation zones included preserved hepatic lobular architecture with a unique hexagonal-like structure. Apoptotic cells were detected, and sinusoidal dilatation and blood congestion were observed, but hepatic arteries and bile ducts were intact around the ablation zones. The early lesions obtained by delivering monophasic square wave pulses through needle electrodes reflected typical histological changes induced by IRE. Therefore, it was found that the histological assessment of the early hepatic lesion after IRE can be utilized to predict the IRE ablation effect.

Protective effect of TPP-Niacin on microgravity-induced oxidative stress and mitochondrial dysfunction of retinal epithelial cells.

Adverse effects of spaceflight on the human body are attritubuted to microgravity and space radiation. One of the most sensitive organs affected by them is the eye, particularly the retina. The conditions that astronauts suffer, such as visual acuity, is collectively called a spaceflight-associated neuro-ocular syndrome (SANS); however, the underlying molecular mechanism of the microgravity-induced ocular pathogenesis is not clearly understood. The current study explored how microgravity affects the retina function in ARPE19 cells in vitro under time-averaged simulated microgravity (µG) generated by clinostat. We found multicellular spheroid (MCS) formation and a significantly decreased cell migration potency under µG conditions compared to 1G in ARPE19 cells. We also observed that µG increases intracellular reactive oxygen species (ROS) and causes mitochondrial dysfunction in ARPE19 cells. Subsequently, we showed that µG activates autophagic pathways and ciliogenesis. Furthermore, we demonstrated that mitophagy activation is triggered via the mTOR-ULK1-BNIP3 signaling axis. Finally, we validated the effectiveness of TPP-Niacin in mitigating µG-induced oxidative stress and mitochondrial dysfunction in vitro, which provides the first experimental evidence for TPP-Niacin as a potential therapeutic agent to ameliorate the cellular phenotypes caused by µG in ARPE19 cells. Further investigations are, however, required to determine its physiological functions and biological efficacies in primary human retinal cells, in vivo models, and target identification.

Tumor-mediated 4-1BB induces tumor proliferation and metastasis in the colorectal cancer cells.

AIMS: 4-1BB is a member of the tumor necrosis factor receptor superfamily that mainly expressed on activated T-cells and plays important roles in cell proliferation and survival of T-cells and natural killer cells. The roles of 4-1BB in immune cells have been intensively studied, whereas little is known about the expression and roles of 4-1BB in cancer cells. MAIN METHODS: In the present study, we investigated 4-1BB expression in colorectal cancer tissues from human patients and established colorectal cancer cells, using mRNA expression, FACS, and immunostaining. Cancer cell proliferation and metastasis regulated by transfected 4-1BB was evaluated by cell growth rate, colony forming assay, cell migration, and Western blot with antibodies which are involved in epithelial-mesenchymal transition and anti-apoptosis. Expression of 4-1BB was knockdown by 4-1BB shRNA to prove that 4-1BB was involved in the cell proliferation. In vivo, 4-1BB transfected cancer cells were injected into mice, to induce tumor local region or lung. KEY FINDINGS: We found that colorectal cancer tissues from human patients and established colorectal cancer cells expressed 4-1BB at the high level. The higher expression of 4-1BB proliferated faster. In addition, we identified two forms of 4-1BB detected in colorectal cancer cells: full length form that was located on the plasma membrane and a short soluble form in the cytosol. The soluble form was also detected in the plasma from the mice with tumor xenografts expressed 4-1BB. SIGNIFICANCE: Tumor-mediated 4-1BB expression in the colorectal cancer cells showed effects on cancer cell proliferation, invasion, and metastasis.

Anti-multiple myeloma potential of resynthesized belinostat derivatives: an experimental study on cytotoxic activity, drug combination, and docking studies.

Multiple myeloma is a deadly cancer that is a complex and multifactorial disease. In the present study, 12 belinostat derivatives (four resynthesized and eight new), HDAC inhibitors, were resynthesized via either Knoevenagel condensation, or Wittig reaction, or Heck reaction. Then an evaluation of the antiproliferative activities against myeloma cells MOPC-315 was carried out. Amongst them, compound 7f was the most bioactive compound with an IC50 of 0.090 ± 0.016 µM, being 3.5-fold more potent than the reference belinostat (IC50 = 0.318 ± 0.049 µM). Furthermore, we also confirmed the inhibitory activity of 7f in a cellular model. Additionally, we found that the inhibitory activity of 7f against histone deacetylase 6 catalytic activity (HDAC6) is more potent than that of belinostat. Finally, we observed the strong synergistic interaction between the derivative 7f and the proteasome bortezomib inhibitor (CI = 0.26), while belinostat and bortezomib showed synergism with a CI value of 0.36. Taken together, the above results suggest that 7f is a promising HDAC inhibitor deserving further investigation.

Pheophorbide A and SN38 conjugated hyaluronan nanoparticles for photodynamic- and cascadic chemotherapy of cancer stem-like ovarian cancer.

In this study, we designed photo-triggered reactive oxygen species (ROS)-generating pheophorbide A and ROS-cleavable thioketal-SN38 conjugated hyaluronan-cholesterol nanoparticles (PheoA-SN38-HC NPs). And we observed the combined therapeutic effects of PheoA-SN38-HC NPs against HEY-T30 human ovarian cancer (OC) model. Clinical Proteomic Tumor Analysis Consortium (CPTAC) data showed that the expression of cancer stem cell (CSC) markers (CD44, ALDH1A1, and CD117) is highly associated with poor clinical outcomes in OC patients. We proved that HEY-T30 cells overexpress CSC markers and much more invasive than other cancer cells. Flow cytometry (FACS) and microscopic analysis revealed the active targeting property of PheoA-SN38-HC NPs to CD44+ HEY-T30 cells. Moreover, the combination therapeutic effect of PheoA-SN38-HC NPs was clearly demonstrated against in vitro HEY-T30 cells and an in vivo xenograft mouse model. In particular, the paracrine cytotoxic effect of SN38 probably compensates the locoregional therapeutic limitation of photodynamic therapy.

Target Design of Novel Histone Deacetylase 6 Selective Inhibitors with 2-Mercaptoquinazolinone as the Cap Moiety.

Epigenetic alterations found in all human cancers are promising targets for anticancer therapy. In this sense, histone deacetylase inhibitors (HDACIs) are interesting anticancer agents that play an important role in the epigenetic regulation of cancer cells. Here, we report 15 novel hydroxamic acid-based histone deacetylase inhibitors with quinazolinone core structures. Five compounds exhibited antiproliferative activity with IC50 values of 3.4-37.8 µM. Compound 8 with a 2-mercaptoquinazolinone cap moiety displayed the highest antiproliferative efficacy against MCF-7 cells. For the HDAC6 target selectivity study, compound 8 displayed an IC50 value of 2.3 µM, which is 29.3 times higher than those of HDAC3, HDAC4, HDAC8, and HDAC11. Western blot assay proved that compound 8 strongly inhibited tubulin acetylation, a substrate of HDAC6. Compound 8 also displayed stronger inhibition activity against HDAC11 than the control drug Belinostat. The inhibitory mechanism of action of compound 8 on HDAC enzymes was then explored using molecular docking study. The data revealed a high binding affinity (-7.92 kcal/mol) of compound 8 toward HDAC6. In addition, dock pose analysis also proved that compound 8 might serve as a potent inhibitor of HDAC11.

Enhanced thermodynamic, pharmacokinetic and theranostic properties of polymeric micelles via hydrophobic core-clustering of superparamagnetic iron oxide nanoparticles.

BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIO) have been applied for decades to design theranostic polymeric micelles for targeted cancer therapy and diagnostic MR imaging. However, the effects of SPIO on the physicochemical, and biological properties of polymeric micelles have not yet been fully elucidated. Therefore, we investigated potential effect of SPIO on the physical and biological properties of theranostic polymeric micelles using representative cancer drug (doxorubicin; Doxo) and polymer carrier (i.e., poly (ethylene glycol)-co-poly(D,L-lactide), PEG-PLA). METHODS: SPIO were synthesized from Fe(acetyl acetonate)3 in an aryl ether. SPIO and Doxo were loaded into the polymeric micelles by a solvent-evaporation method. We observed the effect of SPIO-clustering on drug loading, micelle size, thermodynamic stability, and theranostic property of PEG-PLA polymeric micelles. In addition, cellular uptake behaviors, pharmacokinetic and biodistribution study were performed. RESULTS: SPIO formed hydrophobic geometric cavity in the micelle core and significantly affected the integrity of micelles in terms of micelle size, Doxo loading, critical micelle concentration (CMC) and in vitro dissociation. In vivo pharmacokinetic studies also showed the enhanced Area Under Curve (AUC) and elongated the half-life of Doxo. CONCLUSIONS: Clustered SPIO in micelles largely affects not only MR imaging properties but also biological and physical properties of polymeric micelles.

Retinoic acid-conjugated chitosan/manganese porphyrin ionic-complex nanoparticles for improved T1 contrast MR imaging of hepatic fibrosis.

Noninvasive and precise diagnosis of hepatic fibrosis is very important for the preventive therapeutic regimen of hepatic cirrhosis and cancer. In this study, we fabricated T1 contrast Mn-porphyrin (MnTPPS4 )/retinoic acid-chitosan ionic-complex nanoparticles (MRC NPs). The functional properties of MRC NPs were evaluated via transmission electron microscopy (TEM) imaging, release study, cytotoxicity assay, hepatocyte-specific uptake assay, and magnetic resonance (MR) imaging study. TEM images confirmed the typical structure of an ionic-complex NPs with around 100-200 nm of diameter. MnTPPS4 is released from MRC NPs for up to 24 hr in controlled pattern which implies that more reliable and convenient hepatic MR imaging is possible using of MRC NPs in clinical practice. Hepatocytes uptake assay proved retinoic acid-specific targeting of MRC NPs. The same results were observed in animal pharmacokinetic studies. In vitro MR phantom study, MRC NPs showed an increased T1 relaxivity (r1  = 6.772 mM-1  s-1 ) in comparison with 3.242 mM-1  s-1 of MnTPPS4 . The result was confirmed again in vivo MR imaging studies. Taken together, MRC NPs displayed a potential for noninvasive diagnostic T1 MR imaging of hepatic fibrosis with improved target specificity and prolonged MR imaging time window.

Enhanced Therapeutic Potential of Irreversible Electroporation under Combination with Gold-Doped Mesoporous Silica Nanoparticles against EMT-6 Breast Cancer Cells.

Irreversible electroporation (IRE) is a non-thermal tumor ablation technique that delivers short pulses of strong electric fields to cancer tissues and induces cell death through the destruction of cell membranes. Here, we synthesized gold-doped mesoporous silica nanoparticles (Au-MSNs) via incipient wetness impregnation and evaluated the therapeutic potentials of combination therapy with IRE. The fabricated Au-MSNs had around 80-100 nm of particle size and were successfully end-doped with Au nanoparticles. Combination treatment of IRE (800 V/cm) and Au-MSNs (100 µg/mL) increased cell membrane permeability by 25-fold compared with single IRE treatment. Cellular reactive oxygen species (ROS) and lipid peroxidation of EMT-6 cells were significantly increased by 14- and 265-fold, respectively, under combination treatment of IRE (800 V/cm) and Au-MSNs (100 µg/mL). Cytotoxic cell death increased by 28% under a combination treatment of IRE (800 V/cm) and Au-MSNs (100 ug/mL) over single IRE. Our studies suggest that the combination treatment of IRE with Au-MSNs can enhance the therapeutic efficacy of IRE for breast cancer.

The effects of real and simulated microgravity on cellular mitochondrial function.

Astronauts returning from space shuttle missions or the International Space Station have been diagnosed with various health problems such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance including visual acuity, altered metabolic and nutritional status, and immune system dysregulation. These health issues are associated with oxidative stress caused by a microgravity environment. Mitochondria are a source of reactive oxygen species (ROS). However, the molecular mechanisms through which mitochondria produce ROS in a microgravity environment remain unclear. Therefore, this review aimed to explore the mechanism through which microgravity induces oxidative damage in mitochondria by evaluating the expression of genes and proteins, as well as relevant metabolic pathways. In general, microgravity-induced ROS reduce mitochondrial volume by mainly affecting the efficiency of the respiratory chain and metabolic pathways. The impaired respiratory chain is thought to generate ROS through premature electron leakage in the electron transport chain. The imbalance between ROS production and antioxidant defense in mitochondria is the main cause of mitochondrial stress and damage, which leads to mitochondrial dysfunction. Moreover, we discuss the effects of antioxidants against oxidative stress caused by the microgravity environment space microgravity in together with simulated microgravity (i.e., spaceflight or ground-based spaceflight analogs: parabolic flight, centrifugal force, drop towers, etc.). Further studies should be taken to explore the effects of microgravity on mitochondrial stress-related diseases, especially for the development of new therapeutic drugs that can help increase the health of astronauts on long space missions.

Design and clinical developments of aptamer-drug conjugates for targeted cancer therapy.

BACKGROUND: Aptamer has been called "chemical antibody" which displays the specific affinity to target molecules compared to that of antibodies and possesses several therapeutic advantages over antibodies in terms of size, accessibility to synthesis, and modification. Based on the attractive properties, aptamers have been interested in many directions and now are emerged as new target-designed cancer drug. MAIN BODY: Currently, new types of aptamers have been reported and attracted many scientists' interesting. Due to simplicity of chemical modification and ready-made molecular engineering, scientists have developed newly designed aptamers conjugated with a wide range of therapeutics, aptamer-drug conjugates; ApDCs, from chemotherapy to phototherapy, gene therapy, and vaccines. ApDCs display synergistic therapeutic effects in cancer treatment. CONCLUSION: In this paper, we reviewed various kinds of ApDCs, i.e., ApDC nucleotide analogs, ApDC by drug intercalation, and ApDC by using chemical linker. Current data prove these ApDCs have sufficient potential to complete clinical development soon. Advanced technology of cancer drug delivery and combination treatment of cancers enables aptamer and conjugated drug (ApDCs) efficient means for targeted cancer treatment that reduces potential toxicity and increases therapeutic efficacy.

Bisphosphonate-Conjugated Photo-Crosslinking Polyanionic Hyaluronic Acid Microbeads for Controlled BMP2 Delivery and Enhanced Bone Formation Efficacy.

In this study, we designed bisphosphonate-conjugated polyanionic hyaluronic acid (HA) microbeads (MBs) for the controlled delivery of bone morphogenetic protein 2 (BMP2). MBs were prepared via the photo-crosslinking of bisphosphonate (alendronate)-conjugated methacrylated HA (Alen-MHA). The polyanionic Alen-MHA MBs actively absorbed cationic BMP2 up to 91.0% of the loading efficacy and displayed a sustained release of BMP2 for 10 days. BMP2/Alen-MHA MBs induced osteogenic-related genes in cellular experiments and showed the highly increased bone formation efficacy in thigh muscle injection and rat spinal fusion animal models. Thus, BMP2/Alen-MHA MBs provide a promising opportunity to improve the delivery efficiency of BMP2.

Acetazolamide-eluting biodegradable tubular stent prevents pancreaticojejunal anastomotic leakage.

Postoperative pancreatic fistula at the early stage can lead to auto-digestion, which may delay the recovery of the pancreaticojejunal (PJ) anastomosis. The efficacy and safety of an acetazolamide-eluting biodegradable tubular stent (AZ-BTS) for the prevention of self-digestion and intra-abdominal inflammatory diseases caused by pancreatic juice leakage after PJ anastomosis in a porcine model were investigated. The AZ-BTS was successfully fabricated using a multiple dip-coating process. Then, the drug amount and release profile were analyzed. The therapeutic effects of AZ were examined in vitro using two kinds of pancreatic cancer cell lines, AsPC-1 and PANC-1. The efficacy of AZ-BTS was assessed in a porcine PJ leakage model, with animals were each assigned to a leakage group, a BTS group and an AZ-BTS group. The overall mortality rates in these three groups were 44.4%, 16.6%, and 0%, respectively. Mean α-amylase concentrations were significantly higher in the leakage and BTS groups than in the AZ-BTS group on day 2-5 (p < 0.05 each all). The luminal diameters and areas of the pancreatic duct were significantly larger in the leakage group than in the BTS and AZ-BTS groups (p < 0.05 each all). These findings indicate that AZ-BTS can significantly suppress intra-abdominal inflammatory diseases caused by pancreatic juice leakage and also prevent late stricture formation at the PJ anastomotic site in a porcine model.

Improved effect of a mitochondria-targeted antioxidant on hydrogen peroxide-induced oxidative stress in human retinal pigment epithelium cells.

BACKGROUND: Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells. METHODS: The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR). RESULTS: TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from the H2O2-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1). CONCLUSION: We verified the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1α, NRF2, HO-1, and NQO-1, in RPE cells.

T1-Positive Mn2+-Doped Multi-Stimuli Responsive poly(L-DOPA) Nanoparticles for Photothermal and Photodynamic Combination Cancer Therapy.

In this study, we designed near-infrared (NIR)-responsive Mn2+-doped melanin-like poly(L-DOPA) nanoparticles (MNPs), which act as multifunctional nano-platforms for cancer therapy. MNPs, exhibited favorable π-π stacking, drug loading, dual stimuli (NIR and glutathione) responsive drug release, photothermal and photodynamic therapeutic activities, and T1-positive contrast for magnetic resonance imaging (MRI). First, MNPs were fabricated via KMnO4 oxidation, where the embedded Mn2+ acted as a T1-weighted contrast agent. MNPs were then modified using a photosensitizer, Pheophorbide A, via a reducible disulfide linker for glutathione-responsive intracellular release, and then loaded with doxorubicin through π-π stacking and hydrogen bonding. The therapeutic potential of MNPs was further explored via targeted design. MNPs were conjugated with folic acid (FA) and loaded with SN38, thereby demonstrating their ability to bind to different anti-cancer drugs and their potential as a versatile platform, integrating targeted cancer therapy and MRI-guided photothermal and chemotherapeutic therapy. The multimodal therapeutic functions of MNPs were investigated in terms of T1-MR contrast phantom study, photothermal and photodynamic activity, stimuli-responsive drug release, enhanced cellular uptake, and in vivo tumor ablation studies.

Effect of expanding nanocellulose sponge on nasal mucosal defects in an animal model.

Nanocellulose has emerged for a wide range of applications in biomedical engineering because of its water absorption capacity, appropriate elasticity. We investigated the hemostatic and regenerative abilities of an expanding polyvinyl alcohol (PVA)-nanocellulose sponge on nasal mucosal defects. A 3 mm-diameter nasal defect was made in experimental rabbits. Rabbits were divided into four groups with control, vaseline, PVA and PVA-nanocellulose packing groups. After the defect was created, bleeding times and amounts were monitored. Packing materials were removed on experimental day (ED) 2. On ED 3, 7 and 14, histological analysis and immunohistochemical study for neutrophils were performed. Inflammatory cells were counted and epithelial thicknesses were evaluated. Bleeding amounts and times in the vaseline packing group were smaller than in the PVA groups. PVA-nanocellulose group showed less neutrophils than in the other groups on ED 7. Average epithelium thickness in the PVA-nanocellulose group was significantly smaller than in the control group at ED 7, but at ED 14, there was no significant intergroup difference. PVA-nanocellulose group had a significant lower inflammatory cell count than the control group on ED 7. PVA-nanocellulose sponge applied to nasal mucosal defects can significantly enhance mucosal regeneration during early wound healing.

Effects of Helix Geometry on Magnetic Guiding of Helical Polymer Composites on a Gastric Cancer Model: A Feasibility Study.

This study investigates the effects of soft-robot geometry on magnetic guiding to develop an efficient helical mediator on a three-dimensional (3D) gastric cancer model. Four different magnetically active helical soft robots are synthesized by the inclusion of 5-µm iron particles in polydimethylsiloxane matrices. The soft robots are named based on the diameter and length (D2-L15, D5-L20, D5-L25, and D5-L35) with samples having varied helical pitch and weight values. Then, the four samples are tested on a flat surface as well as a stomach model with various 3D wrinkles. We analyze the underlying physics of intermittent magnetomotility for the helix on a flat surface. In addition, we extract representative failure cases of magnetomotility on the stomach model. The D5-L25 sample was the most suitable among the four samples for a helical soft robot that can be moved to a target lesion by the magnetic-flux density of the stomach model. The effects of diameter, length, pitch, and weight of a helical soft robot on magnetomotility are discussed in order for the robot to reach the target lesion successfully via magnetomotility.

Doxycycline-Eluting Core-Shell Type Nanofiber-Covered Trachea Stent for Inhibition of Cellular Metalloproteinase and Its Related Fibrotic Stenosis.

In this study, we fabricated a doxycycline (doxy)-eluting nanofiber-covered endotracheal stent for the prevention of stent intubation-related tissue fibrosis and re-stenosis. The nanofiber was deposited directly on the outer surface of the stent using a coaxial electrospinning method to form a doxy-eluting cover sleeve. Poly(d,l-lactide) was used as the shell-forming polymer and dedicated drug release-control membrane. Polyurethane was selected as the drug-loading core polymer. The compositional ratio of the core to shell was adjusted to 1:0, 1:2, and 1:4 by changing the electro-spray rate of each polymeric solution and microscopic observation of nanofibers using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and the fluorescence microscopy proved core-shell structure of nanofibers. The in vitro release study suggested that the release of doxy could be controlled by increasing the compositional ratio of the shell. The growth of HT1080 fibrosarcoma cells was inhibited by the 10% doxy-containing nanofiber. The real-time polymerase chain reaction (PCR) in HT1080 cells and xenografted tissue models indicated that the doxy-releasing nanofiber inhibited mRNA expression of metalloproteinases (MT1-MMP, MMP-2, and MMP-9). Overall, our study demonstrates that a doxy-eluting core-shell nanofiber stent can be successfully fabricated using coaxial electrospinning and displays the potential to prevent fibrotic re-stenosis, which is the most problematic clinical complication of tracheal stent intubation.