Publications by authors named "Dongwon Lee"

138 Publications

A pilot study evaluating the efficacy and safety of retinaldehyde-loaded niosomes against mild-to-moderate acne.

J Cosmet Dermatol 2021 Sep 29. Epub 2021 Sep 29.

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Background: Retinoids are the mainstay of topical therapy for acne. To improve the efficacy and minimize the side effects of retinoids, various novel drug delivery mechanisms, including nanoparticles, have been developed.

Aim: To evaluate the efficacy and safety of a retinaldehyde-loaded niosome (RA-N) nanoemulsion against sebum secretion and keratinization on mild-to-moderate acne.

Patients/methods: Twenty-three participants exhibiting mild-to-moderate acne with both closed and open comedones were included. They applied a 0.05% RA-N nanoemulsion daily for 4 weeks, did not to use any other emollient or topical pharmaceutical, and were asked to report any symptoms and treatment satisfaction.

Results: The participants demonstrated significantly fewer closed and open comedones after 2 and 4 weeks of treatment than at baseline (*p < 0.05). The mean sebum secretion, measured using Sebumeter®, was 327.95 ± 90.20 μg cm at baseline and reduced to 282.60 ± 99.70 and 250.65 ± 97.6 μg cm , respectively, after 2 and 4 weeks of treatment (*p < 0.05). The mean desquamation index, determined using Visioscan®, was 10.99 ± 1.69 at baseline and decreased to 9.81 ± 1.10 and 8.89 ± 1.32, respectively, after 2 and 4 weeks of treatment (*p < 0.05). The application of the RA-N nanoemulsion resulted in a significantly lower desquamation level, suggesting that the RA-N nanoemulsion was well-tolerated without any skin irritation. None of the participants reported a serious adverse event during this study.

Conclusion: Our findings suggest that the RA-N nanoemulsion was effective in improving comedones in acne-prone skin and safe for long-term application. Further studies are necessary to investigate the long-term effects of the application of the RA-N nanoemulsion in participants with inflammatory acne and acne scars.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocd.14478DOI Listing
September 2021

Inhibition of microsomal prostaglandin E synthase-1 ameliorates acute lung injury in mice.

J Transl Med 2021 08 9;19(1):340. Epub 2021 Aug 9.

Department of BIN Convergence Technology, Chonbuk National University, Jeonju, South Korea.

Background: To examine the effects of BI 1029539 (GS-248), a novel selective human microsomal prostaglandin E synthase-1 (mPGES-1) inhibitor, in experimental models of acute lung injury (ALI) and sepsis in transgenic mice constitutively expressing the mPGES1 (Ptges) humanized allele.

Methods: Series 1: Lipopolysaccharide (LPS)-induced ALI. Mice were randomized to receive vehicle, BI 1029539, or celecoxib. Series 2: Cecal ligation and puncture-induced sepsis. Mice were randomized to receive vehicle or BI 1029539.

Results: Series 1: BI 1029539 or celecoxib reduced LPS-induced lung injury, with reduction in neutrophil influx, protein content, TNF-ɑ, IL-1β and PGE levels in bronchoalveolar lavage (BAL), myeloperoxidase activity, expression of mPGES-1, cyclooxygenase (COX)-2 and intracellular adhesion molecule in lung tissue compared with vehicle-treated mice. Notably, prostacyclin (PGI) BAL concentration was only lowered in celecoxib-treated mice. Series 2: BI 1029539 significantly reduced sepsis-induced BAL inflammatory cell recruitment, lung injury score and lung expression of mPGES-1 and inducible nitric oxide synthase. Treatment with BI 1029539 also significantly prolonged survival of mice with severe sepsis. Anti-inflammatory and anti-migratory effect of BI 1029539 was confirmed in peripheral blood leukocytes from healthy volunteers.

Conclusions: BI 1029539 ameliorates leukocyte infiltration and lung injury resulting from both endotoxin-induced and sepsis-induced lung injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-021-03016-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351447PMC
August 2021

Sequence-based correction of barcode bias in massively parallel reporter assays.

Genome Res 2021 Sep 20;31(9):1638-1645. Epub 2021 Jul 20.

Center for Human Genetics and Genomics, New York University School of Medicine, New York, New York 10016, USA.

Massively parallel reporter assays (MPRAs) are a high-throughput method for evaluating in vitro activities of thousands of candidate -regulatory elements (CREs). In these assays, candidate sequences are cloned upstream or downstream from a reporter gene tagged by unique DNA sequences. However, tag sequences may themselves affect reporter gene expression and lead to major potential biases in the measured -regulatory activity. Here, we present a sequence-based method for correcting tag-sequence-specific effects and show that our method can significantly reduce this source of variation and improve the identification of functional regulatory variants by MPRAs. We also show that our model captures sequence features associated with post-transcriptional regulation of mRNA. Thus, this new method helps not only to improve detection of regulatory signals in MPRA experiments but also to design better MPRA protocols.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/gr.268599.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415370PMC
September 2021

A Lubricated Nonimmunogenic Neural Probe for Acute Insertion Trauma Minimization and Long-Term Signal Recording.

Adv Sci (Weinh) 2021 08 3;8(15):e2100231. Epub 2021 Jun 3.

School of Electrical and Electronic Engineering, Yonsei University, Seoul, 03722, Republic of Korea.

Brain-machine interfaces (BMIs) that link the brain to a machine are promising for the treatment of neurological disorders through the bi-directional translation of neural information over extended periods. However, the longevity of such implanted devices remains limited by the deterioration of their signal sensitivity over time due to acute inflammation from insertion trauma and chronic inflammation caused by the foreign body reaction. To address this challenge, a lubricated surface is fabricated to minimize friction during insertion and avoid immunogenicity during neural signal recording. Reduced friction force leads to 86% less impulse on the brain tissue, and thus immediately increases the number of measured signal electrodes by 102% upon insertion. Furthermore, the signal measurable period increases from 8 to 16 weeks due to the prevention of gliosis. By significantly reducing insertion damage and the foreign body reaction, the lubricated immune-stealthy probe surface (LIPS) can maximize the longevity of implantable BMIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202100231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336494PMC
August 2021

Prediction of Head Movement in 360-Degree Videos Using Attention Model.

Sensors (Basel) 2021 May 25;21(11). Epub 2021 May 25.

Department of Electrical and Electronic Engineering, Hanyang University, Ansan 15588, Korea.

In this paper, we propose a prediction algorithm, the combination of Long Short-Term Memory (LSTM) and attention model, based on machine learning models to predict the vision coordinates when watching 360-degree videos in a Virtual Reality (VR) or Augmented Reality (AR) system. Predicting the vision coordinates while video streaming is important when the network condition is degraded. However, the traditional prediction models such as Moving Average (MA) and Autoregression Moving Average (ARMA) are linear so they cannot consider the nonlinear relationship. Therefore, machine learning models based on deep learning are recently used for nonlinear predictions. We use the Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU) neural network methods, originated in Recurrent Neural Networks (RNN), and predict the head position in the 360-degree videos. Therefore, we adopt the attention model to LSTM to make more accurate results. We also compare the performance of the proposed model with the other machine learning models such as Multi-Layer Perceptron (MLP) and RNN using the root mean squared error (RMSE) of predicted and real coordinates. We demonstrate that our model can predict the vision coordinates more accurately than the other models in various videos.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/s21113678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198419PMC
May 2021

Discriminant Analysis of the Geographical Origin of Asian Red Pepper Powders Using Second-Derivative FT-IR Spectroscopy.

Foods 2021 May 10;10(5). Epub 2021 May 10.

Department of Chemistry, Chung-Ang University, Seoul 06974, Korea.

This study aimed to discriminate between the geographical origins of Asian red pepper powders distributed in Korea using Fourier-transform infrared (FT-IR) spectroscopy coupled with multivariate statistical analyses. Second-derivative spectral data were obtained from a total of 105 red pepper powder samples, 86 of which were used for statistical analysis, and the remaining 19 were used for blind testing. A one-way analysis of variance (ANOVA) test confirmed that eight peak variables exhibited significant origin-dependent differences, and the canonical discriminant functions derived from these variables were used to correctly classify all the red pepper powder samples based on their origins. The applicability of the canonical discriminant functions was examined by performing a blind test wherein the origins of 19 new red pepper powder samples were correctly classified. For simplicity, the four most significant variables were selected as discriminant indicator variables, and the applicable range for each indicator variable was set for each geographical origin. By applying the indicator variable ranges, the origins of the red pepper powders of all the statistical and blind samples were correctly identified. The study findings indicate the feasibility of using FT-IR spectroscopy in combination with multivariate analysis for identifying the geographical origins of red pepper powders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods10051034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150797PMC
May 2021

Theranostic potential of biodegradable polymeric nanoparticles with paclitaxel and curcumin against breast carcinoma.

Biomater Sci 2021 May;9(10):3750-3761

Department of BIN Convergence Technology, Department of Polymer Nano Science & Technology, Jeonbuk National University, Jeonju, 54896, Republic of Korea.

In this study, integrin-mediated targeting and near-infrared fluorescence (NIRF) traceable polyethylene glycol-b-poly(lactic-co-glycolic acid) (PEG-PLGA)-based polymeric nanoparticles (NPs) were prepared to investigate the effects of paclitaxel (PTX) and curcumin (CUR) combination therapy on breast cancer. Cyclic (arginine-glycine-aspartic acid-phenylalanine-lysine) (cRGDfK) was selected as a ligand for breast cancer and conjugated to the end of NPs (cRGDfK-NPs). For fluorescence imaging, sulfo-cyanine 5.5 (Cy5.5) was incorporated into NPs (Cy5.5-NPs). A series of hybrid NPs consisting of NPs, cRGDfK-NPs, and Cy5.5-NPs with drugs encapsulated inside the core (Cy5.5-cRGDfK-NPs/PTX + CUR) were prepared by self-assembly. The efficacy of PTX and CUR combination and the ability of the integrin-mediated targeting of NPs were systemically investigated using a 4T1 mouse breast cancer cell line and a nude mouse xenograft model. We suggested that Cy5.5-cRGDfK-NPs/PTX + CUR has superior theranostic potential against breast carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1bm00370dDOI Listing
May 2021

pH-Responsive Amphiphilic Polyether Micelles with Superior Stability for Smart Drug Delivery.

Biomacromolecules 2021 05 9;22(5):2043-2056. Epub 2021 Apr 9.

Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.

Despite widespread interest in the amphiphilic polymeric micelles for drug delivery systems, it is highly desirable to achieve high loading capacity and high efficiency to reduce the side effects of therapeutic agents while maximizing their efficacy. Here, we present a novel hydrophobic epoxide monomer, cyclohexyloxy ethyl glycidyl ether (CHGE), containing an acetal group as a pH-responsive cleavable linkage. A series of its homopolymers, poly(cyclohexyloxy ethyl glycidyl ether)s (PCHGEs), and block copolymers, poly(ethylene glycol)--poly(cyclohexyloxy ethyl glycidyl ether)s (PEG--PCHGE), were synthesized via anionic ring-opening polymerization in a controlled manner. Subsequently, the self-assembled polymeric micelles of PEG--PCHGE demonstrated high loading capacity, excellent stability in biological media, tunable release efficiency, and high cell viability. Importantly, quantum mechanical calculations performed by considering prolonged hydrolysis of the acetal group in CHGE indicated that the CHGE monomer had higher hydrophobicity than three other functional epoxide monomer analogues developed. Furthermore, the preferential cellular uptake and therapeutic efficacy confirmed the enhanced stability and the pH-responsive degradation of the amphiphilic block copolymer micelles. This study provides a new platform for the development of versatile smart polymeric drug delivery systems with high loading efficiency and tailorable release profiles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.biomac.1c00163DOI Listing
May 2021

The efficacy and safety of multilamellar vesicle containing retinaldehyde: A double-blinded, randomized, split-face controlled study.

J Cosmet Dermatol 2021 Sep 18;20(9):2874-2879. Epub 2021 Feb 18.

Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Background: Retinaldehyde is one of the major members of the retinoid family, which has potential skin rejuvenating effects on photoaged skin and has a good safety profile.

Aims: The study aimed to evaluate the efficacy and safety of multilamellar vesicle containing retinaldehyde (MLV-RAL) 0.05% and 0.1% used to treat photoaged skin.

Patients And Methods: A randomized, prospective, investigator-blinded, split-face comparison study was conducted. We enrolled 23 Korean volunteers who applied MLV-RAL 0.05%/0.1% cream on one randomized side of their face and retinol 0.05%/0.1% cream on the opposite side. Wrinkle depth on both crow's feet was assessed by the Antera 3D system. Skin hydration, elasticity, facial curved length, and dermal density were also evaluated.

Results: After an 8-week application, all objective parameters, including wrinkle depth, were significantly improved in both MLV-RAL 0.05%/0.1% and retinol 0.05%/0.1% treated sides. Compared with the retinol-treated side, MLV-RAL-treated side showed a significant improvement of objective assessments except for dermal density. Additionally, there was no adverse event associated with the use of either MLV-RAL 0.05%/0.1% or retinol 0.05%/0.1% cream.

Conclusion: The application of MLV-RAL 0.05%/0.1% cream improved wrinkle, facial contour, and biophysical parameters associated with skin aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jocd.13993DOI Listing
September 2021

lncRNA MCM3AP-AS1 inhibits the progression of colorectal cancer via the miR-19a-3p/FOXF2 axis.

J Gene Med 2021 03 19;23(3):e3306. Epub 2021 Jan 19.

Department of BIN Convergence Technology and Polymer Nano Science and Technology, Chonbuk National University, Jeonju, Republic of Korea.

Background: Long non-coding RNA MCM3AP antisense RNA 1 (lncRNA MCM3AP-AS1) has a regulatory role in the development of diverse malignancies, whereas its role and mechanism in colorectal cancer (CRC) is not yet clear.

Methods: The relative expression of MCM3AP-AS1, miR-19a-3p and forkhead box F2 (FOXF2) mRNA in 53 cases of CRC and its adjacent normal tissues, human normal colonic mucosal cells (FHC cells) and CRC cell lines was examined by a quantitative real-time polymerase chain reaction, and the changes of cell multiplication and migration were examined by the cell counting kit-8 method, EdU test, and scratch-healing test, respectively. Bioinformatics, dual-luciferase reporter gene assay and a RNA immunoprecipitation experiment were adopted to predict and verify the relationship between MCM3AP-AS1 and miR-19a-3p; bioinformatics and dual-luciferase reporter gene assay were adopted to predict and verify the relationship between miR-19a-3p and FOXF2. Western blotting was executed to examine the effects of MCM3AP-AS1 overexpression or knockdown on FOXF2 protein expression.

Results: MCM3AP-AS1 expression was down-modulated in CRC, and its dysregulation was linked to unfavorable pathological characteristics. MCM3AP-AS1 significantly impeded the multiplication and migration of CRC cells. MCM3AP-AS1 was recognized as a molecular sponge to suppress miR-19a-3p expression, and FOXF2 was a target gene of miR-19a-3p. MCM3AP-AS1 positively modulated FOXF2 expression, and its biological effect was dependent the on miR-19a-3p/FOXF2 axis.

Conclusions: MCM3AP-AS1 can inhibit CRC promoting by modulating the miR-19a-3p/FOXF2 axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgm.3306DOI Listing
March 2021

Lipid Coated and Chlorin e6 Loaded Calcium Carbonate for Effective Immunotheraphy of Colorectal Cancer.

J Biomed Nanotechnol 2020 Aug;16(8):1196-1204

Cancer vaccine is well recognized as a novel but effective way for cancer immunotherapy. Especially, the role of dendritic cells (DCs) in antigen presentation properties is critical for the final performance of cancer vaccine. Herein, a lipid (Li) coated calcium carbonate (CC) vehicle (Li/CC) was employed to load chlorin e6 (Ce6) to serve as a potential vaccine (Li/CC-Ce6) for effective immunotherapy of colorectal cancer. It was suggested that the loaded Ce6 within Li/CCCe6 can be activated under laser irradiation. The photodynamic therapy (PDT) of Ce6 was expected to produce reactive oxygen species (ROS) to cause cell death and expose tumor-associated antigen (TAA). In addition, the produced ROS can mimic the inflammatory responses for the recruitment of DC to initiate strong immune response cascade. Moreover, the recruitment of DC can recognize the exposed TAA to stimulate DC for effective vaccination . Results from and assays demonstrated the strong ability of this platform to enhance DC vaccination, resulting in promising growth inhibition of both primary and distant tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1166/jbn.2020.2965DOI Listing
August 2020

Imaging and Targeted Antibacterial Therapy Using Chimeric Antimicrobial Peptide Micelles.

ACS Appl Mater Interfaces 2020 Dec 25;12(49):54306-54315. Epub 2020 Nov 25.

Department of Polymer Science and Engineering, Sunchon National University, 255 Jungang-ro, Suncheon, Jeollanam-do 57922, Republic of Korea.

Infectious diseases induced by multidrug-resistant bacteria are a challenging problem in medicine because of global rise in the drug resistance to pathogenic bacteria. Despite great efforts on the development of antibiotics and antimicrobial agents, there is still a great need to develop a strategy to early detect bacterial infections and eradicate bacteria effectively and simultaneously. The innate immune systems of various organisms produce antimicrobial peptides, which kill a broad range of bacteria with minimal cytotoxicity to mammalian cells. Therefore, antimicrobial peptides have recently attracted increasing attention as an alternative to conventional antibiotics in antibacterial medications. Here, we report a new family of antibacterial agents, which is formulated from self-assembly of a chimeric antimicrobial lipopeptide (DSPE-HnMc) and amphiphilic biodegradable polymers. HnMc micelles could effectively bind the bacterial membrane to kill a wide spectrum of bacteria and bacterial biofilms. In the studies of mouse models of drug-resistant bacterial infections, HnMc micelles could target bacterial infections with high specificity and also kill drug-resistant bacteria effectively, demonstrating the great potential of HnMc micelles as imaging and targeted antibacterial agents. These findings also provide new insight into the design of antimicrobial peptide-based nanomedicine for detection and treatment of bacterial infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c13083DOI Listing
December 2020

Anchor, Spacer, and Ligand-Modified Engineered Exosomes for Trackable Targeted Therapy.

Bioconjug Chem 2020 11 28;31(11):2541-2552. Epub 2020 Oct 28.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73117, United States.

Exosomes have been widely demonstrated as an effective anticancer therapeutic moiety. However, their clinical translation has been limited by the requirement of prohibitively high therapeutic doses due to their lack of specificity in delivery and, consequently, short systemic half-life. To overcome these challenges, we engineered a platform for modifying exosomes with an active targeting modality composed of membrane Anchor (BODIPY)-Spacer (PEG)-targeting Ligands (cyclic RGD peptide) (ASL). Herein, we show that the intramembrane incorporation of a trackable, targeting system renders ASL exosomes (AExs) a modular platform. AExs significantly overcome challenges associated with exosome modification, including potential damage for functionalization, or destabilizing interactions between dyes and drugs. ASL-modification not only enhanced stability in imparting active targeting but also introduced a built-in bioimaging modality. Our studies show that AExs target B16F10 melanoma tumor sites by the specific interaction of cyclic RGD and integrin. Doxorubicin encapsulated AExs (dAExs) significantly inhibited the growth of melanoma and . Thus, we conclude that ASL-modification allows exosomes to be transformed into a novel therapeutic vehicle uniquely integrating tracking and robust targeting with drug delivery. We anticipate that the therapeutic, targeting, and diagnostic modularity provided by ASL will potentiate translational applications of exosome-based vehicles beyond anticancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.0c00483DOI Listing
November 2020

H2O2-Responsive Antioxidant Nanoparticle Attenuates Whole Body Ischemia/Reperfusion-Induced Multi-Organ Damages.

J Cardiovasc Pharmacol Ther 2021 05 28;26(3):279-288. Epub 2020 Oct 28.

Cardiovascular Institute, 1859Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Mortality and morbidity after cardiac arrest remain high due to ischemia/reperfusion (I/R) injury causing multi-organ damages, even after successful return of spontaneous circulation. We previously generated HO-activatable antioxidant nanoparticles formulated with copolyoxalate containing vanillyl alcohol (PVAX) to prevent I/R injury. In this study, we examined whether PVAX could effectively reduce organ damages in a rat model of whole-body ischemia/reperfusion injury (WBIR). To induce a cardiac arrest, 70µl/100 g body weight of 1 mmol/l potassium chloride was administered via the jugular venous catheter. The animals in both the vehicle and PVAX-treated groups had similar baseline blood pressure. After 5.5 minutes of cardiac arrest, animals were resuscitated via intravenous epinephrine followed by chest compressions. PVAX or vehicle was injected after the spontaneous recovery of blood pressure was noted, followed by the same dose of second injection 10 minutes later. After 24 hours, multiple organs were harvested for pathological, biochemical, molecular analyses. No significant difference on the restoration of spontaneous circulation was observed between vehicle and PVAX groups. Analysis of organs harvested 24 hours post procedure showed that whole body I/R significantly increased reactive oxygen species (ROS) generation, inflammatory markers, and apoptosis in multiple organs (heart, brain, and kidney). PVAX treatment effectively blocked ROS generation, reduced the elevation of pro-inflammatory cytokines, and decreased apoptosis in these organs. Taken together, our results suggest that PVAX has potent protective effect against WBIR induced multi-organ injury, possibly by blocking ROS-mediated cell damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1074248420969571DOI Listing
May 2021

Tunable Piezoelectricity of Multifunctional Boron Nitride Nanotube/Poly(dimethylsiloxane) Stretchable Composites.

Adv Mater 2020 Oct 21;32(43):e2004607. Epub 2020 Sep 21.

Advanced Materials and Processing Branch, NASA Langley Research Center, Hampton, VA, 23681, USA.

Boron nitride nanotubes (BNNT) uniformly dispersed in stretchable materials, such as poly(dimethylsiloxane) (PDMS), could create the next generation of composites with augmented mechanical, thermal, and piezoelectric characteristics. This work reports tunable piezoelectricity of multifunctional BNNT/PDMS stretchable composites prepared via co-solvent blending with tetrahydrofuran (THF) to disperse BNNTs in PDMS while avoiding sonication or functionalization. The resultant stretchable BNNT/PDMS composites demonstrate augmented Young's modulus (200% increase at 9 wt% BNNT) and thermal conductivity (120% increase at 9 wt% BNNT) without losing stretchability. Furthermore, BNNT/PDMS composites demonstrate piezoelectric responses that are linearly proportional to BNNT wt%, achieving a piezoelectric constant (|d |) of 18 pmV at 9 wt% BNNT without poling, which is competitive with commercial piezoelectric polymers. Uniquely, BNNT/PDMS accommodates tensile strains up to 60% without plastic deformation by aligning BNNTs, which enhances the composites' piezoelectric response approximately five times. Finally, the combined stretchable and piezoelectric nature of the composite was exploited to produce a vibration sensor sensitive to low-frequency (≈1 kHz) excitation. This is the first demonstration of multifunctional, stretchable BNNT/PDMS composites with enhanced mechanical strength and thermal conductivity and furthermore tunable piezoelectric response by varying BNNT wt% and applied strain, permitting applications in soft actuators and vibration sensors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202004607DOI Listing
October 2020

Bile acid-based dual-functional prodrug nanoparticles for bone regeneration through hydrogen peroxide scavenging and osteogenic differentiation of mesenchymal stem cells.

J Control Release 2020 12 15;328:596-607. Epub 2020 Sep 15.

Department of Medical Biotechnology, Dongguk University, 04620 Seoul, South Korea. Electronic address:

A high level of reactive oxygen species (ROS) such as hydrogen peroxide (HO) upregulates pro-inflammatory cytokines and inhibits the osteogenic differentiation of mesenchymal stem cells (MSCs), which are key factors in bone regeneration. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has antioxidant and anti-inflammatory activities and also plays beneficial roles in bone regeneration by stimulating the osteogenic differentiation of MSCs while suppressing their adipogenic differentiation. Despite its remarkable capacity for bone regeneration, multiple injections of UDCA induce adverse side effects such as mechanical stress and contamination in bone defects. To fully exploit the beneficial roles of UDCA, a concept polymeric prodrug was developed based on the hypothesis that removal of overproduced HO will potentiate the osteogenic functions of UDCA. In this work, we report bone regenerative nanoparticles (NPs) formulated from a polymeric prodrug of UDCA (PUDCA) with UDCA incorporated in its backbone through HO-responsive peroxalate linkages. The PUDCA NPs displayed potent antioxidant and anti-inflammatory activities in MSCs and induced osteogenic rather than adipogenic differentiation of the MSCs. In rat models of bone defect, the PUDCA NPs exhibited significantly better bone regeneration capacity and anti-inflammatory effects than equivalent amounts of UDCA. We anticipate that PUDCA NPs have tremendous translational potential as bone regenerative agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2020.09.023DOI Listing
December 2020

Dexamethasone-loaded HO-activatable anti-inflammatory nanoparticles for on-demand therapy of inflammatory respiratory diseases.

Nanomedicine 2020 11 14;30:102301. Epub 2020 Sep 14.

Department of BIN Convergence Technology, Jeonbuk National University, Jeonju, Jeonbuk, Republic of Korea; Department of Bionanotechnology and Bioconvergence Engineering, Jeonbuk National University, Jeonju, Jeonbuk, Republic of Korea; Department of Polymer Nano Science and Technology, Jeonbuk National University, Jeonju, Jeonbuk, Republic of Korea. Electronic address:

Asthma is a common airway inflammatory disorder, characterized by increased infiltration of leukocytes and bronchoconstriction. Dexamethasone (DEX) has been widely used in the treatment of allergic asthma. However, long-term and frequent use of DEX has side effects. We therefore reasoned that if drug carriers have intrinsic anti-inflammatory and anti-asthmatic activity and synergize with drug payloads, a low dose of DEX could exert sufficient therapeutic effects. In this study, we developed DEX-loaded HO-activatable boronate maltodextrin (DEX-BM) nanoparticles. DEX-BM nanoparticles released DEX in a HO-triggered manner and remarkably suppressed the expression of pro-inflammatory cytokines in activated macrophages and lung epithelial cells. In the studies of a murine allergic asthma model, DEX-BM nanoparticles (5 mg/kg) effectively inhibited the inflammatory cell infiltration and airway inflammation than equivalent DEX and BM nanoparticles without noticeable side effects. We anticipate that DEX-BM nanoparticles hold great potential as therapeutic agents for various airway inflammatory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nano.2020.102301DOI Listing
November 2020

Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome.

Kidney Int 2020 11 14;98(5):1308-1322. Epub 2020 Jun 14.

Department of Pediatrics, Chonnam National University Children's Hospital, Gwangju, Korea.

To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (P=6.71E-28, OR=1.88) and TNFSF15 (P=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101291PMC
November 2020

Neuropeptide Y incorporated into PVAX nanoparticle improves angiogenesis in a murine model of myocardial ischemia.

Eur J Pharmacol 2020 Sep 10;882:173261. Epub 2020 Jun 10.

Department of Anesthesia, Critical Care and Pain Medicine, Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, USA. Electronic address:

Neuropeptide-Y (NPY) leads to angiogenesis and remodeling of the ischemic myocardium. The objective of this study is to assess the therapeutic potential of NPY in a model of acute myocardial ischemia using a nanoparticles delivery system targeted to tissue with oxidative stress. NPY was loaded onto copolyoxalate containing vanillyl alcohol (PVAX) using a double emulsification strategy. Adult C57BL/J6 mice (n = 49) were randomly divided into PVAX-NPY (n = 22), Vehicle (Saline) (n = 16), and Sham (n = 11) groups. The ischemia to left anterior descending artery was induced in PVAX-NPY or vehicle groups. The tissue was collected at the end of two weeks after assessing the functional and echocardiographic data. There was a significant decrease in infarction size and mortality in PVAX-NPY group compared to the Vehicle group (P = 0.01 and P = 0.05). On echocardiography, there was significant improvement in contractility and diastolic parameters (P = 0.01). On pressure-volume loop there was significant increase in stroke volume (P = 0.01), cardiac output (P = 0.01) and ventricular stroke work (P = 0.01) in the PVAX-NPY group. On Western blot analysis, there was a significant increase in pro-angiogenic factors Ang-1, TGF-β, PDGF- β and its receptors and VEGF in the ischemic tissue treated with PVAX-NPY as compared to Vehicle ischemic tissue (P = 0.01, P = 0.0003, and P < 0.05 respectively). It may be possible to have targeted delivery of labile neurotransmitters NPY to the ischemic myocardium using nanoparticle PVAX and achieving angiogenesis and significant functional improvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2020.173261DOI Listing
September 2020

FakeNewsNet: A Data Repository with News Content, Social Context, and Spatiotemporal Information for Studying Fake News on Social Media.

Big Data 2020 06;8(3):171-188

Department of Computer Science and Engineering, Arizona State University, Tempe, Arizona, USA.

Social media has become a popular means for people to consume and share the news. At the same time, however, it has also enabled the wide dissemination of , that is, news with intentionally false information, causing significant negative effects on society. To mitigate this problem, the research of fake news detection has recently received a lot of attention. Despite several existing computational solutions on the detection of fake news, the lack of comprehensive and community-driven fake news data sets has become one of major roadblocks. Not only existing data sets are scarce, they do not contain a myriad of features often required in the study such as , , and . Therefore, in this article, to facilitate fake news-related research, we present a fake news data repository , which contains two comprehensive data sets with diverse features in , , and . We present a comprehensive description of the FakeNewsNet, demonstrate an exploratory analysis of two data sets from different perspectives, and discuss the benefits of the FakeNewsNet for potential applications on fake news study on social media.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/big.2020.0062DOI Listing
June 2020

Analysis of putative cis-regulatory elements regulating blood pressure variation.

Hum Mol Genet 2020 07;29(11):1922-1932

Department of Genetic Medicine, McKusick-Nathans Institute, Baltimore, MD 21205, USA.

Hundreds of loci have been associated with blood pressure (BP) traits from many genome-wide association studies. We identified an enrichment of these loci in aorta and tibial artery expression quantitative trait loci in our previous work in ~100 000 Genetic Epidemiology Research on Aging study participants. In the present study, we sought to fine-map known loci and identify novel genes by determining putative regulatory regions for these and other tissues relevant to BP. We constructed maps of putative cis-regulatory elements (CREs) using publicly available open chromatin data for the heart, aorta and tibial arteries, and multiple kidney cell types. Variants within these regions may be evaluated quantitatively for their tissue- or cell-type-specific regulatory impact using deltaSVM functional scores, as described in our previous work. We aggregate variants within these putative CREs within 50 Kb of the start or end of 'expressed' genes in these tissues or cell types using public expression data and use deltaSVM scores as weights in the group-wise sequence kernel association test to identify candidates. We test for association with both BP traits and expression within these tissues or cell types of interest and identify the candidates MTHFR, C10orf32, CSK, NOV, ULK4, SDCCAG8, SCAMP5, RPP25, HDGFRP3, VPS37B and PPCDC. Additionally, we examined two known QT interval genes, SCN5A and NOS1AP, in the Atherosclerosis Risk in Communities Study, as a positive control, and observed the expected heart-specific effect. Thus, our method identifies variants and genes for further functional testing using tissue- or cell-type-specific putative regulatory information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddaa098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372556PMC
July 2020

MCCC2 overexpression predicts poorer prognosis and promotes cell proliferation in colorectal cancer.

Exp Mol Pathol 2020 08 20;115:104428. Epub 2020 Mar 20.

Department of BIN Convergence Technology and Polymer Nano Science and Technology, Chonbuk National University, 664-14, Dukjin, Jeonju 561-756, Republic of Korea. Electronic address:

Purposes: Recently, Methylcrotonoyl-CoA carboxylase 2 (MCCC2) is reported to be involved in tumor formation and progression. However, MCCC2 has nerve been reported in colorectal cancer. In this study, we aimed to investigate the role of MCCC2 in colorectal cancer.

Methods: 118 colorectal cancer and matched adjacent normal tissues were enrolled in this study. The expression level of MCCC2 was measured by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The clinical significance of MCCC2 and its influence on cell proliferation was further analyzed.

Results: Results shown that the mRNA levels of MCCC2 in colorectal cancer tissues were significantly increased compared with those in normal tissues (P < .0001). MCCC2 high-expression was observed in 56.8% colorectal cancer tissues, which was significantly higher than those in normal controls (9.3%, P < .0001). MCCC2 high-expression correlated with tumor size, T stage, lymph node metastasis, distant metastasis, clinical stage and differentiation in colorectal cancer (P < .05). Moreover, MCCC2 high-expression predicted poorer prognosis and could be as an independent prognostic factor. In addition, MCCC2 knockdown significantly inhibited cell proliferation compared with these controls, while MCCC2 overexpression could reverse the effect.

Conclusion: These data indicate MCCC2 overexpression promotes cell proliferation and predicts poorer prognosis in colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexmp.2020.104428DOI Listing
August 2020

Targeting of intragraft reactive oxygen species by APP-103, a novel polymer product, mitigates ischemia/reperfusion injury and promotes the survival of renal transplants.

Am J Transplant 2020 06 22;20(6):1527-1537. Epub 2020 Feb 22.

Division of Transplant Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Inflammatory responses associated with ischemia/reperfusion injury (IRI) play a central role in alloimmunity and transplant outcomes. A key event driving these inflammatory responses is the burst of reactive oxygen species (ROS), with hydrogen peroxide (H O ) as the most abundant form that occurs as a result of surgical implantation of the donor organ. Here, we used a syngeneic rat renal transplant and IRI model to evaluate the therapeutic properties of APP-103, a polyoxalate-based copolymer molecule containing vanillyl alcohol (VA) that exhibits high sensitivity and specificity toward the production of H O . We show that APP-103 is safe, and that it effectively promotes kidney function following IRI and survival of renal transplants. APP-103 reduces tissue injury and IRI-associated inflammatory responses in models of both warm ischemia (kidney clamping) and prolonged cold ischemia (syngeneic renal transplant). Mechanistically, we demonstrate that APP-103 exerts protective effects by specifically targeting the production of ROS. Our data introduce APP-103 as a novel, nontoxic, and site-activating therapeutic approach that effectively ameliorates the consequences of IRI in solid organ transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.15794DOI Listing
June 2020

Acid-sensitive oxidative stress inducing and photoabsorbing polysaccharide nanoparticles for combinational anticancer therapy.

Int J Pharm 2020 Jan 22;574:118893. Epub 2019 Nov 22.

Department of BIN Convergence Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea; Department of Polymer⋅Nano Science and Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea. Electronic address:

Combination therapy, a treatment regimen that combines more than two therapeutic agents to diseased tissues has recently gained increasing attentions in anticancer therapy. As cancer cells are more vulnerable to oxidative stress and heat compared to normal cells, we developed hyperthermia- and oxidative stress-inducing maltodextrin (HTOM) nanoparticles as a platform of combinational photothermal/oxidative anticancer therapy. HTOM was designed to incorporate cinnamaldehyde as an oxidative stress inducer through acid-labile acetal linkage and IR780 as a photoabsorber. HTOM nanoparticles could generate excess reactive oxygen species (ROS) to kill cancer cells effectively. When exposed to near infrared (NIR) laser irradiation (808 nm), HTOM nanoparticles also increased temperature to destroy cancer cells. The combination of NIR laser irradiation with HTOM nanoparticles exhibited significantly higher anticancer activity than HTOM nanoparticles alone and NIR lasers irradiation alone. When combined with NIR laser irradiation on the tumor site, intravenously administrated HTOM nanoparticles effectively eradicated tumors in mouse xenograft models. Our strategy for combination of oxidative stress and photothermal heating may offer a new combinational treatment modality for cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpharm.2019.118893DOI Listing
January 2020

Acid-activatable polymeric curcumin nanoparticles as therapeutic agents for osteoarthritis.

Nanomedicine 2020 01 28;23:102104. Epub 2019 Oct 28.

Department of BIN Convergence Technology, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea; Department of Polymer·Nano Science and Technology, Chonbuk National University, Jeonju, Chonbuk, Republic of Korea. Electronic address:

Curcumin, a primary active element of turmeric, has potent antioxidant and anti-inflammatory activity, but its low bioavailability is a major hurdle in its pharmaceutical applications. To enhance the therapeutic efficacy of curcumin, we exploited polymeric prodrug strategy. Here, we report rationally designed acid-activatable curcumin polymer (ACP), as a therapeutic prodrug of curcumin, in which curcumin was covalently incorporated in the backbone of amphiphilic polymer. ACP could self-assemble to form micelles that rapidly release curcumin under the acidic condition. The potential of ACP micelles as therapeutics for osteoarthritis was evaluated using a mouse model of monoidoacetic acid (MIA)-induced knee osteoarthritis. ACP micelles drastically protected the articular structures from arthritis through the suppression of tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Given their pathological stimulus-responsiveness and potent antioxidant and anti-inflammatory activities, ACP micelles hold remarkable potential as a therapeutic agent for not only osteoarthritis but also various inflammatory diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nano.2019.102104DOI Listing
January 2020

Glutathione-Depleting Pro-Oxidant as a Selective Anticancer Therapeutic Agent.

ACS Omega 2019 Jun 10;4(6):10070-10077. Epub 2019 Jun 10.

Department of BIN Convergence Technology and Department of Polymer Nano Science and Technology, Chonbuk National University, Backjedaero 567, Jeonju 54896, Republic of Korea.

A main challenge in the development of anticancer drugs that eradicate cancer cells specifically with minimal toxicity to normal cells is to identify the cancer-specific properties. Cancer cells sustain a higher level of reactive oxygen species, owing to metabolic and signaling aberrations and unrestrained growth. Cancer cells are also furnished with a powerful reducing environment, owing to the overproduction of antioxidants such as glutathione (GSH). Therefore, the altered redox balance is probably the most prevailing property of cancer cells distinct from normal cells, which could serve as a plausible therapeutic target. In this work, we developed a GSH-depleting pro-oxidant, benzoyloxy dibenzyl carbonate, termed B2C, which is capable of rapidly declining GSH and elevating oxidative stress to a threshold level above which cancer cells cannot survive. B2C was designed to release quinone methide (QM) that rapidly depletes GSH through esterase-mediated hydrolysis. B2C was able to rapidly deplete GSH and induce an overwhelming level of oxidative stress in cancer cells, leading to mitochondrial disruption, activation of procaspase-3 and PARP-1, and cleavage of Bcl-2. In the study of tumor xenograft models, intravenously injected B2C caused apoptotic cell death in tumors and significantly suppressed tumor growth. These findings provide a new insight into the design of more effective anticancer drugs, which exploit altered redox balance in cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.9b00140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648603PMC
June 2019

Interfering with long chain noncoding RNA ANRIL expression reduces heart failure in rats with diabetes by inhibiting myocardial oxidative stress.

J Cell Biochem 2019 10 18;120(10):18446-18456. Epub 2019 Jun 18.

Department of Polymer_Nano Science and Technology, Polymer Fusion Research Center, Chonbuk National University, Jeonju, Korea.

This study is performed to elucidate whether long-chain noncoding RNA ANRIL has an effect on diabetes, and further explore the mechanism of ANRIL in diabetes. The rat model of diabetes was established via intraperitoneal injection of streptozotocin. The modeled rats were grouped into normal, diabetes, siRNA-NC, and ANRIL siRNA groups. Besides, the expression of ANRIL, cardiac function, inflammatory factor levels, cardiomyocyte apoptosis, and levels of oxidative stress index were all determined. Upregulated ANRIL was found in myocardial tissue of diabetic rats. Downregulated ANRIL improved cardiac function index and the expression of inflammatory factors, improved the pathological state of myocardial tissue and myocardial remodeling, decreased myocardial collagen deposition area and cardiomyocyte apoptosis and reduced the oxidative level of myocardial tissue in diabetic rats. This present study suggests that upregulated ANRIL is found in myocardial tissue of diabetic rats. Additionally, silencing of ANRIL reduces myocardial injury in diabetes by inhibiting myocardial oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcb.29162DOI Listing
October 2019

Thrombus targeting aspirin particles for near infrared imaging and on-demand therapy of thrombotic vascular diseases.

J Control Release 2019 06 10;304:164-172. Epub 2019 May 10.

Department of BIN Convergence Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea; Department of Polymer·Nano Science and Technology, Chonbuk National University, Baekjedaero 567, Jeonju, Chonbuk 54896, Republic of Korea. Electronic address:

A blood clot (thrombus) is formed as a final product of the hemostatic process with two major components, a mesh of cross-linked fibrin and platelets activated by high concentration of hydrogen peroxide (HO). Thrombus formation impedes blood flow to brain and heart and is a principle cause of life-threatening diseases such as stroke and myocardial infarction. Aspirin has been widely used for the treatment and prevention of various cardiovascular diseases, but is unable to target a thrombus and scavenge a high level of HO. In this study, we report thrombus targeting aspirin polyconjugate particles (T-APP) as a near infrared imaging agent and on-demand therapeutic agent for thrombotic vascular diseases. T-APP were formulated from HO-activatable aspirin polyconjugate, fibrin-specific peptides and fluorescent IR780. In mouse models of tail bleeding and arterial thrombosis, T-APP targeted the thrombosed vessels rapidly with excellent specificity. T-APP also exerted highly strong antithrombotic activity in the thrombosed vessel by suppressing anti-inflammatory cytokines and inhibiting platelet activation. Based on the unique features such as specific thrombus targeting, HO scavenging, and on-demand therapeutic actions, the rationally engineered T-APP have important ramifications on imaging and on-demand therapy of thrombotic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2019.05.012DOI Listing
June 2019

Multiple variant enhancers modulate its cardiac gene expression and the QT interval.

Proc Natl Acad Sci U S A 2019 05 8;116(22):10636-10645. Epub 2019 May 8.

Center for Human Genetics and Genomics, New York University School of Medicine, New York, NY 10016;

The rationale for genome-wide association study (GWAS) results is sequence variation in -regulatory elements (CREs) modulating a target gene's expression as the major cause of trait variation. To understand the complete molecular landscape of one of these GWAS loci, we performed in vitro reporter screens in cardiomyocyte cell lines for CREs overlapping nearly all common variants associated with any of five independent QT interval (QTi)-associated GWAS hits at the - locus. We identified 13 causal CRE variants using allelic reporter activity, cardiomyocyte nuclear extract-based binding assays, overlap with human cardiac tissue DNaseI hypersensitive regions, and predicted impact of sequence variants on DNaseI sensitivity. Our analyses identified at least one high-confidence causal CRE variant for each of the five sentinel hits that could collectively predict cardiac gene expression and QTi association. Although all 13 variants could explain gene expression, the highest statistical significance was obtained with seven variants (inclusive of the five above). Thus, multiple, causal, mutually associated CRE variants can underlie GWAS signals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1808734116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6561183PMC
May 2019

Engineered Polymeric Micelles for Combinational Oxidation Anticancer Therapy through Concurrent HO-1 Inhibition and ROS Generation.

Biomacromolecules 2019 02 14;20(2):1109-1117. Epub 2019 Jan 14.

Cancer cells have a large amount of ROS (reactive oxygen species) because of disturbed ROS homeostasis. Cancer cells therefore undertake redox adaptation to drive proliferation in tumor environments and even survive during anticancer treatment by upregulating endogenous antioxidants. As one of antioxidant defense systems, heme oxygenase-1 (HO-1) acts as an essential role in tumor development by offering antioxidant bilirubin to protect cancer cells under stress conditions. It can be therefore reasoned that the combination of ROS generation and HO-1 inhibition would exert synergistic anticancer effects through the amplification of oxidative stress and provide a new opportunity for targeted anticancer therapy. To establish targeted anticancer therapy based on amplified oxidative stress, we developed molecularly engineered polymer, termed CZP, which incorporates ROS generating CA (cinnamaldehyde) and HO-1 inhibiting ZnPP (zinc protoporphyrin) in its backbone and could form stable micelles in aqueous solutions. CZP micelles not only elevated oxidative stress but also suppressed the expression of antioxidant HO-1, leading to apoptotic cell death. CZP micelles could also significantly suppress the tumor growth without body weight loss, tumor recurrence, and noticeable toxicity in organs. This study demonstrates that a combination of ROS generation and HO-1inhibition synergistically magnifies oxidative stress to kill cancer cells and oxidative stress amplifying CZP micelles may provide a promising strategy in anticancer treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.biomac.8b01802DOI Listing
February 2019
-->