Nanographene-Au fine-tuning to intensify plasmonic-resonance of polymeric hybrid bionanosystem for synergistic phototherapy and nerve photobiomodulation.

Here, we report the multi-photo-bioactivity of the plasmonic-nano graphitic coordinated polycaprolactone-based aligned nanofibrous scaffolds-based bionanosystem for photothermal breast and colon cancer therapies and peripheral nerve photobiomodulation. The size-optimized colloidal reduced graphene oxide (nRGO, 180 nm) nanosheets, for enhanced photothermal impact, were surface-functionalized with gold nanospheres (AuNPs) to prepare the nRGO@AuNP monodispersed nano-composite and then doped 2.0 mg of nRGO@AuNP in biocompatible and biodegradable polymer polycaprolactone (PCL) to fabricate the nRGO@AuNP-PCL (2.0 mg) plasmonic aligned nanofibrous scaffolds. More than 90% of cancer cells, breast cancer (MCF-7) as well as colon cancer (CT-26), ablated after 5 min of low NIR (808 nm) laser power (0.72 W/cm2) illumination with nRGO@AuNP-PCL (2.0 mg) aligned nanofibrous scaffolds. Besides, the nRGO@AuNP-PCL (2.0 mg) provided an extraordinary microenvironment for adhesion, nerve growth, proliferation, and differentiation of PC12 and S42 cells which mimics the natural extracellular matrix. The 2.5-fold increase in neurite length was observed with NIR illumination after 3 days whereas 1.7-fold was found without NIR illumination after 7 days in comparison to PCL (pure). The current findings will be useful to provide a new crucial approach for preparing biocompatible multifunctional composite plasmonic nanofibers as a highly efficient distinct platform for photothermal therapies and promising bioimplants to overcome the loss of sensation after cancer surgery through nerve photobiomodulation.

Current status of nutritional provision and effects of nutritional support on the clinical outcomes of acute kidney injury requiring continuous renal replacement therapy in the surgical intensive care unit.

BACKGROUND AND OBJECTIVES: Patients with acute kidney injury requiring continuous renal replacement therapy are at high risk of malnutrition. Nutritional support is an important part of treatment for patients with critical illness admitted to the intensive care unit. We aimed to investigate the status of nutritional provision and the effects of nutritional support on clinical outcomes. METHODS AND STUDY DESIGN: Our institution's medical records (from January 1, 2020, to December 31, 2021) were analyzed in this retrospective cohort study. We included 43 patients aged >18 years who received continuous renal replacement therapy for acute kidney injury in the surgical intensive care unit. RESULTS: The demographic characteristics were similar between the survivor and non-survivor groups. The protein supply per body weight (0.88 ± 0.37 g/kg vs. 0.47 ± 0.53 g/kg, p = 0.029) and the proportion of patients who met the target protein level (58.9 ± 24.9% vs. 30.8 ± 34.9%, p = 0.022) were significantly higher in the survivor group. Approximately 79.1% of the patients had a high malnutrition risk with a modified Nutrition Risk in the Critically Ill score of ≥5. The lengths of hospital and intensive care unit stays were longer in the high nutritional risk group compared with that in the low nutritional risk group, but the result was not significant. CONCLUSIONS: The nutritional amount provided in patients with critical illness is significantly lesser than the recommended amount. Ensuring proper nutritional support can improve the clinical outcomes.

Near-Infrared Responsive Synergistic Chemo-Phototherapy from Surface-Functionalized Poly(ε-caprolactone)-Poly(d,l-lactic-co-glycolic acid) Composite Nanofibers for Postsurgical Cancer Treatment.

The combination of hyperthermia and chemotherapy has attracted significant attention in local cancer treatment following surgical resection. Pyrrole is a potent photothermal agent that can induce a temperature rise at different concentrations in the surrounding medium by absorbing near-infrared radiation (NIR). In this study, poly(ε-caprolactone) (PCL) and poly (d,l-lactic-co-glycolic acid) (PLGA) were used to make nanofibers using the electrospinning process. Then, pyrrole in different concentrations of (0.2, 0.4, and 0.6) M was attached to the surface of PCL-PLGA fiber mats by in situ polymerization, which was confirmed by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD) analysis. A concentration-dependent local temperature rise was observed using a FLIR camera under near-infrared (NIR) laser irradiation. For the hyperthermia effect, pyrrole concentration (0.06 M) was used for in vitro drug release studies and cell viability assays because under NIR irradiation (2 W/cm2, 3 min), it increased the local temperature to around 45 °C. In vitro drug release studies confirmed that NIR irradiation increased the diffusion rate of doxorubicin (DOX) by increasing the environmental temperature above the glass transition temperature of PLGA. In vitro cytotoxicity experiments further confirmed that PCL-PLGA-DOX/PPy fiber mats showed an enhanced inhibitory effect against CT26 and MCF7 cells by the combination of hyperthermia and chemotherapy.

Nanogap-containing thermo-plasmonic nano-heaters for amplified photo-triggered tumor ablation at low laser power density.

Herein, nanogap amplified plasmonic heat-generators are fabricated by decorating Pt nanodots on gold nanospheres (GNSs@Pt@mPEG) by maintaining strategic nano-gaps (1-2 nm) and studied precisely for plasmonic photothermal therapy (PPTT) of colon cancer by passive tumor targeting. The surface modification of GNSs@Pt with poly(ethylene glycol) methyl ether thiol (mPEG) increases their accumulation in tumor cells and hence the GNSs@Pt@mPEG stay at the tumor site for a longer time. The nanogap amplified GNSs@Pt@mPEG (O.D. = 4.0) generated high plasmonic photothermal hyperthermia and utilized a low NIR power density (0.36 W cm-2) for the elimination of tumor cells in only 150 s of irradiation time and shows excellent colloidal and photo-stability. The predominant distribution of GNSs@Pt@mPEG caused effective tumor cell death and promoted uniform treatment on tumor sites. In vivo studies demonstrated that the GNSs@Pt@mPEG have very low toxicity, high biocompatibility, and thermal stability, stay longer at the tumor site, induce tumor cell death without side effects, and show significantly less uptake in other organs except for the spleen. The significant accumulations and longer stay suggested that they are favorable for tumor passive uptake and the possibility of enhanced PPTT after intravenous administration. The nano-particles were stable up to O.D. 200 and have at least 12 months shelf-life without losing colloidal stability or photothermal efficacy. These findings lay the groundwork for using GNSs@Pt@mPEG as a NIR light-responsive PPTT agent and demonstrated their potential for further use in clinical applications.

Fabrication of Three-Dimensional Alginate Porous Scaffold Incorporated with Decellularized Cornu Cervi Pantotrichum Particle for Bone Tissue Engineering.

Deer antler velvet (DAV), Cornu Cervi Pantotrichum, has been known for the outstanding growth rate and used in extracted liquid form in oriental herbal medicine for the tissue regeneration. The DAV is also famous for the abundance of many different minerals, proteins, growth factors and interleukins. The immense amount of DAV is consumed to produce DAV extract in Asian countries. However, the mechanical strength and the morphologic features of DAV have been overlooked. In this study, we revisited the possibility of DAV as a bone tissue scaffold. We first obtained DAV particles via physical decellularization followed by levigation procedure and then applied to the fabrication of three-dimensional porous alginate/DAVP sponge through lyophilizing alginate/DAVP hydrogel as a potential bone tissue scaffold source. The morphological and physicochemical properties of alginate/DAVP sponge were characterized using UTM, SEM, FE-SEM, and FT-IR. The alginate-based highly porous sponge demonstrated the interconnected porous structure with DAVP and improved mechanical properties. We expected both alginate/DAVP and DAVP are potential for tissue engineering application.

Synthesis of polypyrrole nanorods via sacrificial removal of aluminum oxide nanopore template: A study on cell viability, electrical stimulation and neuronal differentiation of PC12 cells.

Synthesis of nanomaterials having uniform shape and size is a challenging task. Properties exhibited by such substrates would be compatible and homogeneous compared to the average properties displayed by those substrates with heterogeneous size. Herein, we report the synthesis of polypyrrole nanorods (PPy-NRs) of almost uniform size via oxidative chemical polymerization of pyrrole within anodized aluminum oxide nanopores followed by sacrificial removal of the template. Field emission scanning electron microscopy (FE-SEM), fourier transformed infra-red (FT-IR) spectra, X-ray diffraction (XRD), and ultra-violet-visible-near infra-red (UV-Vis-NIR) spectra of the substrate were used to analyze the physicochemical properties of as-synthesized PPy-NRs. PPy-NRs treated MC3T3-E1 and PC12 cells exhibited good biocompatibility in CCK-8 and live/dead assays. The assay showed more cell viability on PC12 cell lines. Electrical stimulation through PPy-NRs treated PC12 cells accelerated neuronal differentiation compared to those without electrical stimulation during in vitro cell culture.

Polydopamine-based Implantable Multifunctional Nanocarpet for Highly Efficient Photothermal-chemo Therapy.

We report a design and fabricate multifunctional localized platform for cancer therapy. Multiple stimuli-responsive polydopamine (PDA) was used for surface modification of electrospun doxorubicin hydrochloride (DOX) loaded polycaprolactone (PCL) fibers to make a designated platform. Photothermal properties such as photothermal performance and stability of the resulting composite mats were studied under the irradiation of the near-infrared (NIR) laser of 808 nm. With the incorporation of PDA into the fiber, a remarkable increase of local temperature was recorded under NIR illumination in a concentration-dependent manner with excellent stability. Drug released assay results revealed PDA coated PCL-DOX mats showed pH and NIR dual responsive behavior thereby exhibiting improved drug release in an acidic medium compared to physiological pH condition (pH 7.4) which is further increased by NIR exposure. The cancer activity in vitro of the mats was evaluated using cell counting (CCK) and live and dead cell assays. The combined effect of NIR mediated hyperthermia and chemo release resulting improved cells death has been reported. In summary, this study presents a major step forward towards a therapeutic model to cancer treatment utilizing pH and NIR dual responsive property from PDA alone in a fibrous mat.

Sacrificial template-based synthetic approach of polypyrrole hollow fibers for photothermal therapy.

In the present work, polypyrrole hollow fibers (PPy-HFs) were fabricated by sacrificial removal of soft templates of electrospun polycaprolactone (PCL) fibers with polypyrrole (PPy) coating through chemical polymerization of pyrrole monomer. Different physicochemical properties of as-fabricated PPy-HFs were then studied by Field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), Fourier transform infra-red (FT-IR) spectroscopy, Differential scanning calorimetry/Thermogravimetric analysis (DSC/TGA), and X-ray photoelectron spectroscopy (XPS). The photothermal activity of PPy-HF was studied by irradiating 808-nm near infra-red (NIR) light under different power values with various concentrations of PPy-HFs dispersed in phosphate buffer solution (PBS, pH 7.4). These PPy-HFs exhibited enhanced photothermal performance compared with polypyrrole nanoparticles (PPy-NPs). Furthermore, these PPy-HFs showed photothermal effect that was laser-power- and concentration-dependent. The photothermal toxicity of the resulting nanofiber was evaluated using cell counting kit-8 (CCK-8) and live and dead cell assays. Results showed that these PPy-HFs were more effective in killing cancer cells under NIR irradiation. In contrast, hollow-fiber showed no cytotoxicity without NIR exposure. Among different nanofiber formulations, PPy-160 exhibited the highest photothermal toxicity. It could be explained by its enhanced photothermal performance compared to other specimens. The resulting PPy-HFs showed superior drug-loading capacity to PPy-NPs. This might be attributed to adequate binding of the drug into both luminal and abluminal hollow-fiber surfaces. Fabrication of this substrate type opens a promising new avenue for architectural design of biocompatible organic polymer for biomedical field.

Short duration cancer treatment: inspired by a fast bio-resorbable smart nano-fiber device containing NIR lethal polydopamine nanospheres for effective chemo-photothermal cancer therapy.

BACKGROUND: The objective of this study was to evaluate the efficacy of a combination of Photothermal therapy (PTT) and chemotherapy in a single nano-fiber platform containing lethal polydopamine nanopheres (PD NPs) for annihilation of CT 26 cancer cells. METHOD: Polydioxanone (PDO) nanofiber containing PD and bortezomib (BTZ) was fabricated via electrospinning method. The content of BTZ and PD after optimization was 7% and 2.5% respectively with respect to PDO weight. PD NPs have absorption band in near-infrared (NIR) with resultant rapid heating capable of inducing cancer cell death. The samples was divided into three groups - PDO, PDO+PD, and PDO+PD-BTZ for analysis. RESULTS: In combined treatment, PDO nanofiber alone could not inhibit cancer cell growth as it neither contain PD or BTZ. However, PDO+PD fiber showed a cell viability of approximately 20% after 72 hr of treatment indicating minimal killing via hyperthermia. In the case of PDO composite fiber containing BTZ, the effect of NIR irradiation reduced the viability of cancer cells down to around 5% after 72 h showing the efficiency of combination therapy on cancer cells elimination. However, due to higher photothermal conversion that may negatively affect normal cells above 46°C, we have employed 1 s "OFF" and 2 s "ON" after initial 9 s continuous irradiation to maintain the temperature between 42 and 46°C over 3 mins of treatment using 2 W/cm2; 808 nm laser which resulted to similar cell death. CONCLUSION: In this study, combination of PTT and chemotherapy treatment on CT 26 colon cancer cells within 3 min resulted in effective cell death in contrast to single treatment of either PTT and chemotherapy alone. Our results suggest that this nanofiber device with efficient heating and remote control drug delivery system can be useful and convenient in the future clinical application for localized cancer therapy.

Hexa-functional tumour-seeking nano voyagers and annihilators for synergistic cancer theranostic applications.

In order to meet the unmet medical needs for effective cancer treatment, multifunctional nanocarriers based on iron oxide nanoparticles hold tremendous promise. Here we report a superparamagnetic iron oxide nanoparticles based hexa-functional nanosystem for synergistic cancer theranostic applications by offering active tumour targeting, accumulation and complementary imaging capability by combining magnetic resonance imaging as well as near-infrared fluorescence, magnetophotothermia and chemotherapy. The uniquely designed nanosystem exhibited a paramount increase in the antitumour efficacy through the simultaneous application of multiple thermal effects called magnetophotothermia, which outweighed the therapeutic efficacy of the current thermo-chemo therapies or stand-alone therapies. The active tumour-seeking property with prolonged tumour accumulation and complementary imaging capability with improved sensitivity and resolution also augments the therapeutic efficacy of the proposed nanosystem. Additionally, the work proposes a deep-learning-based tumour cell nuclei detection technique from H&E stained images in anticipation of providing much inspiration for the future of precision histology.

Implantable chemothermal brachytherapy seeds: A synergistic approach to brachytherapy using polymeric dual drug delivery and hyperthermia for malignant solid tumor ablation.

Chemothermal brachytherapy seeds have been developed using a combination of polymeric dual drug chemotherapy and alternating magnetic field induced hyperthermia. The synergistic effect of chemotherapy and hyperthermia brachytherapy has been investigated in a way that has never been performed before, with an in-depth analysis of the cancer cell inhibition property of the new system. A comprehensive in vivo study on athymic mice model with SCC7 tumor has been conducted to determine optimal arrays and specifications of the chemothermal seeds. Dual drug chemotherapy has been achieved via surface deposition of polydopamine that carries bortezomib, and also via loading an acidic pH soluble hydrogel that contains 5-Fluorouracil inside the chemothermal seed; this increases the drug loading capacity of the chemothermal seed, and creates dual drug synergism. An external alternating magnetic field has been utilized to induce hyperthermia conditions, using the inherent ferromagnetic property of the nitinol alloy used as the seed casing. The materials used in this study were fully characterized using FESEM, H1 NMR, FT-IR, and XPS to validate their properties. This new approach to experimental cancer treatment is a pilot study that exhibits the potential of thermal brachytherapy and chemotherapy as a combined treatment modality.

Discovery of a Novel Highly Selective Histamine H4 Receptor Antagonist for the Treatment of Atopic Dermatitis.

The histamine H4 receptor (H4R), a member of the G-protein coupled receptor family, has been considered as a potential therapeutic target for treating atopic dermatitis (AD). A large number of H4R antagonists have been disclosed, but no efficient agents controlling both pruritus and inflammation in AD have been developed yet. Here, we have discovered a novel class of orally available H4R antagonists showing strong anti-itching and anti-inflammation activity as well as excellent selectivity against off-targets. A pharmacophore-based virtual screening system constructed in-house successfully identified initial hit compound 9, and the subsequent homology model-guided optimization efficiently led us to discover pyrido[2,3- e]tetrazolo[1,5- a]pyrazine analogue 48 as a novel chemotype of a potent and highly selective H4R antagonist. Importantly, orally administered compound 48 exhibits remarkable efficacy on antipruritus and anti-inflammation with a favorable pharmacokinetic (PK) profile in several mouse models of AD. Thus, these data strongly suggest that our compound 48 is a promising clinical candidate for treatment of AD.

On-demand drug release and hyperthermia therapy applications of thermoresponsive poly-(NIPAAm-co-HMAAm)/polyurethane core-shell nanofiber mat on non-vascular nitinol stents.

A functional cover made up of core-shell nanofibers with a unique combination of thermoresponsive polymeric shell and stretchable polymeric core for non-vascular nitinol stents that uses an alternating magnetic field (AMF) to induce heat in the stent for hyperthermia therapy and simultaneously release 5-fluorouracil and/or paclitaxel was designed. Varying the ratios of NIPAAm to HMAAm monomer resulted in different LCST properties for the synthesized copolymer and further utilized for an on-demand drug release. Biocompatibility test using NIH-3T3 fibroblast cells indicates that the composite with drug content is biocompatible and the in-vitro cancer cytotoxicity test using ESO26 and OE21 cancer cells proved that the material shows cancer cytotoxic properties via combination of dual drug and hyperthermia therapy. With this functional material, we propose a tailorable and on-demand drug release with more control that can be employed for a combination drug therapy/single drug therapy combined with hyperthermia therapy for cancer cytotoxicity effect.

pH/NIR Light-Controlled Multidrug Release via a Mussel-Inspired Nanocomposite Hydrogel for Chemo-Photothermal Cancer Therapy.

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia. On the other hand, facile release of the anticancer drug BTZ from the surface of DP encapsulated hydrogel could be achieved due to the dissociation between catechol groups of DP and the boronic acid functionality of BTZ in typical acidic cancer environment. In order to increase the synergistic effect by dual drug delivery, Doxorubicin (DOXO) were also loaded to pNIPAAm-co-pAAm/DP-BTZ hydrogel and the effect of monotherapy as well as combined therapy were detailed by a complete characterization. Our results suggest that these mussel inspired nanocomposite with excellent heating property and controllable multidrug release can be considered as a potential material for cancer therapy.

Development of polyamide-6,6/chitosan electrospun hybrid nanofibrous scaffolds for tissue engineering application.

The development of biofunctional and bioactive hybrid polymeric scaffolds seek to mitigate the current challenges in the emerging field of tissue engineering. In this paper, we report the fabrication of a biomimetic and biocompatible nanofibrous scaffolds of polyamide-6,6 (PA-6,6) blended with biopolymer chitosan via one step co-electrospinning technique. Different weight percentage of chitosan 10wt%, 15wt%, and 20wt% were blended with PA-6,6, respectively. The nanocomposite electrospun scaffolds mats enabled to provide the osteophilic environment for cells growth and biomineralization. The morphological and physiochemical properties of the resulted scaffolds were studied using field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and Fourier transform-infrared (FT-IR) spectroscopy. The improvement in hydrophilicity and mechanical strength of the bio-nanocomposite mesh with 20wt% chitosan embedded, was the desired avenue for adhesion, proliferation and maturation of osteoblast cells as compared to other sample groups and pure PA-6,6 fibrous mat. The biomineralization of the nanocomposite electrospun mats also showed higher ability to nucleate bioactive calcium phosphate (Ca/P) nanoparticles comparing to pristine PA-6,6. Furthermore, the biomimetic nature of scaffolds exhibited the cells viability and regeneration of pre-osteoblast (MC3T3-E1) cells which were assessed via in vitro cell culture test. Collectively, the results suggested that the optimized 20wt% of chitosan supplemented hybrid electrospun fibrous scaffold has significant effect in biomedical field to create osteogenic capabilities for tissue engineering.

Multifunctional Nanocarpets for Cancer Theranostics: Remotely Controlled Graphene Nanoheaters for Thermo-Chemosensitisation and Magnetic Resonance Imaging.

A new paradigm in cancer theranostics is enabled by safe multifunctional nanoplatform that can be applied for therapeutic functions together with imaging capabilities. Herein, we develop a multifunctional nanocomposite consisting of Graphene Oxide-Iron Oxide -Doxorubicin (GO-IO-DOX) as a theranostic cancer platform. The smart magnetic nanoplatform acts both as a hyperthermic agent that delivers heat when an alternating magnetic field is applied and a chemotherapeutic agent in a cancer environment by providing a pH-dependent drug release to administer a synergistic anticancer treatment with an enhanced T2 contrast for MRI. The novel GO-IO-DOX nanocomposites were tested in vitro and were observed to exhibit an enhanced tumoricidal effect through both hyperthermia and cancer cell-specific DOX release along with an excellent MRI performance, enabling a versatile theranostic platform for cancer. Moreover the localized antitumor effects of GO-IO-DOX increased substantially as a result of the drug sensitization through repeated application of hyperthermia.

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. STATEMENT OF SIGNIFICANCE: The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a pH-sensitive manner. This implantable magnetic nanofiber device can be exploited to apply hyperthermia with an alternating magnetic field and to achieve cancer cell-specific drug release to enable synergistic cancer therapy, which results in an improvement in both quality of life and patient compliance.

A smart magnetic nanoplatform for synergistic anticancer therapy: manoeuvring mussel-inspired functional magnetic nanoparticles for pH responsive anticancer drug delivery and hyperthermia.

We report the versatile design of a smart nanoplatform for thermo-chemotherapy treatment of cancer. For the first time in the literature, our design takes advantage of the outstanding properties of mussel-inspired multiple catecholic groups - presenting a unique copolymer poly(2-hydroxyethyl methacrylate-co-dopamine methacrylamide) p(HEMA-co-DMA) to surface functionalize the superparamagnetic iron oxide nanoparticles as well as to conjugate borate containing anticancer drug bortezomib (BTZ) in a pH-dependent manner for the synergistic anticancer treatment. The unique multiple anchoring groups can be used to substantially improve the affinity of the ligands to the surfaces of the nanoparticles to form ultrastable iron oxide nanoparticles with control over their hydrodynamic diameter and interfacial chemistry. Thus the BTZ-incorporated-bio-inspired-smart magnetic nanoplatform will act as a hyperthermic agent that delivers heat when an alternating magnetic field is applied while the BTZ-bound catechol moieties act as chemotherapeutic agents in a cancer environment by providing pH-dependent drug release for the synergistic thermo-chemotherapy application. The anticancer efficacy of these bio-inspired multifunctional smart magnetic nanoparticles was tested both in vitro and in vivo and found that these unique magnetic nanoplatforms can be established to endow for the next generation of nanomedicine for efficient and safe cancer therapy.

Electrotransfection of mammalian cells using microchannel-type electroporation chip.

Transfection of DNA molecules into mammalian cells with electric pulsations, which is so-called electroporation, is a powerful and widely used method that can be directly applied to gene therapy. However, very little is known about the basic mechanisms of DNA transfer and cell response to the electric pulse. We developed a microelectroporation chip with poly(dimethylsiloxane) (PDMS) to investigate the mechanism of electroporation as a first step of DNA transfer and to introduce the benefits of miniaturization into the genetic manipulation. The microelectroporation chip has a microchannel with a height of 20 microm and a length of 2 cm. Owing to the transparency of PDMS, we could in situ observe the uptake process of propidium iodide (PI) into SK-OV-3 cells, which shows promise in visualization of gene delivery in living cells. We also noticed the geometric effect on the degree of electroporation in microchannels with diverse channel width. This experimental result shows that the geometry can be another parameter to be considered for the electroporation when it is performed in microchannels with an exponential decaying pulse generator. Cell culturing is possible within the microelectroporation chip, and we also successfully transfected SK-OV-3 cells with enhanced green fluorescent protein genes, which demonstrates the feasibility of the microelectroporation chip in genetic manipulation.

Soamsan, a traditional Korean medicine, enhances antigen-specific immune responses in low-responder mice via the combined activity of glycoproteins and endotoxins.

Soamsan is a traditional anti-cancer treatment in oriental medicine. It is thought that this material modulates immune responses. To determine whether Soamsan treatment has any effect on the induction of antigen-specific immune responses, C57BL/6 mice, which are low-responders to hen egg-white lysozyme (HEL), were injected with HEL, and their specific immune responses were measured while they were fed Soamsan. Oral administration of Soamsan enhanced the anti-HEL antibody response as well as the T-cell proliferative response to the antigen. Analyses of the HEL-specific antibody isotypes showed that Soamsan treatment resulted in increased levels of HEL-specific antibodies, irrespective of isotype. In particular, however, HEL-specific antibodies of the IgG2b, IgG3, and IgM isotypes, which are associated with direct stimulation of B cells, were significantly increased by the Soamsan treatment. Stimulation of C57BL/6 splenocytes in vitro showed that the presence of Soamsan significantly augmented the proliferative activity induced by both B and T cell mitogens. This augmentation was associated with glycoprotein(s) with a molecular weight mass of about 100 kDa, as well as with endotoxin-like compounds. These results suggest that Soamsan modulates and enhances antigen-specific immune responses.