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1.
ACS Nano ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38975706

ABSTRACT

Electrolytic ablation (EA) is a burgeoning treatment for solid tumors, in which electrical energy catalyzes a chemical reaction to generate reactive species that can eradicate cancer cells. However, the application of this technique has been constrained owing to the limited spatial effectiveness and complexity of the electrode designs. Therefore, the incorporation of nanotechnology into EA is anticipated to be a significant improvement. Herein, we present a therapeutic approach based on difructose dianhydride IV-conjugated polyethylenimine-polyethylene glycol-modified gold nanorods as electric nanoantennas and nanoelectrocatalysts for EA. We demonstrate that square-wave direct current (DC) fields trigger a reaction between water molecules and chloride ions on the gold nanorod surface, generating electrolytic products including hydrogen, oxygen, and chlorine gases near the electrodes, changing the pH, and inducing cell death. These electric nanoantennas showed significant efficacy in treating colorectal cancer both in vitro and in vivo after DC treatment. These findings clearly indicate that gold nanoantennas enhance the effectiveness of EA by creating a localized electric field and catalyzing electrolytic reactions for the induction of locoregional pH changes within the tumor. By overcoming the limitations of traditional EA and offering an enhanced level of tumor specificity and control, this nanotechnology-integrated approach advances further innovations in cancer therapies.

2.
Pharmaceutics ; 16(2)2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38399337

ABSTRACT

Phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), combined with novel all-in-one light-responsive nanocomposites have recently emerged as new therapeutic modalities for the treatment of cancer. Herein, we developed novel all-in-one triphenylphosphonium-functionalized gold nanorod/zinc oxide core-shell nanocomposites (CTPP-GNR@ZnO) for mitochondrial-targeted PTT/PDT owing to their good biocompatibility, tunable and high optical absorption, photothermal conversion efficiency, highest reactive oxygen species (ROS) generation, and high mitochondrial-targeting capability. Under laser irradiation of 780 nm, the CTPP-GNR@ZnO core-shell nanocomposites effectively produced heat in addition to generating ROS to induce cell death, implying a synergistic effect of mild PTT and PDT in combating cancer. Notably, the in vitro PTT/PDT effect of CTPP-GNR@ZnO core-shell nanocomposites exhibited effective cell ablation (95%) and induced significant intracellular ROS after the 780 nm laser irradiation for 50 min, indicating that CTPP in CTPP-GNR@ZnO core-shell nanocomposites can specifically target the mitochondria of CT-26 cells, as well as generate heat and ROS to completely kill cancer cells. Overall, this light-responsive nanocomposite-based phototherapy provides a new approach for cancer synergistic therapy.

3.
Stem Cell Res ; 75: 103303, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38211411

ABSTRACT

Human induced pluripotent stem cells (hiPSCs) have potential use in regerenrative medicine for disease modeling and drug screening studies. The AAVS1 locus has been validated as a stable transgene expression and safe genomic location. Therefore, we inserted the enhanced green fluorescent protein (EGFP) gene into the AAVS1 locus of hiPSCs, using CRISPR/Cas9 genome editing. The results showed that the hiPSCs stably expressed EGFP in pluripotency and differentiated into three germ lineages. Our results strongly indicate that the EGFP-tagged cell line has potential for use in in vivo and in vitro experiments for monitoring cell location and type.


Subject(s)
Induced Pluripotent Stem Cells , Humans , Induced Pluripotent Stem Cells/metabolism , CRISPR-Cas Systems/genetics , Cell Line , Green Fluorescent Proteins/metabolism
4.
Pharmaceutics ; 16(1)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38276508

ABSTRACT

Precision diagnosis-guided efficient treatment is crucial to extending the lives of cancer patients. The integration of surface-enhanced Raman scattering (SERS) imaging and phototherapy into a single nanoplatform has been considered a more accurate diagnosis and treatment strategy for cancer nanotheranostics. Herein, we constructed a new type of mesoporous silica-layered gold nanorod core@silver shell nanostructures loaded with methylene blue (GNR@Ag@mSiO2-MB) as a multifunctional nanotheranostic agent for intracellular SERS imaging and phototherapy. The synthesized GNR@Ag@mSiO2-MB nanostructures possessed a uniform core-shell structure, strong near-infrared (NIR) absorbance, photothermal conversion efficiency (65%), dye loading ability, SERS signal, and Raman stability under phototherapy conditions. Under single 785 nm NIR laser irradiation, the intracellular GNR@Ag@mSiO2-MB nanostructures were dramatically decreased to <9%, which showed excellent photothermal and photodynamic effects toward cancer cell killing, indicating that the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) of the GNR@Ag@mSiO2-MB nanostructures could greatly enhance the therapeutic efficacy of cancer cell death. GNR@Ag@mSiO2-MB nanostructures demonstrated a strong Raman signal at 450 and 502 cm-1, corresponding to the δ(C-N-C) mode, suggesting that the Raman bands of GNR@Ag@mSiO2-MB nanostructures were more efficient to detect CT-26 cell SERS imaging with high specificity. Our results indicate that GNR@Ag@mSiO2-MB nanostructures offer an excellent multifunctional nanotheranostic platform for SERS imaging and synergistic anticancer phototherapy in the future.

5.
Adv Mater ; 36(14): e2310130, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38145576

ABSTRACT

Optical encryption using coloration and photoluminescent (PL) materials can provide highly secure data protection with direct and intuitive identification of encrypted information. Encryption capable of independently controlling wavelength-tunable coloration as well as variable light intensity PL is not adequately demonstrated yet. Herein, a rewritable PL and structural color (SC) display suitable for dual-responsive optical encryption developed with a stimuli-responsive SC of a block copolymer (BCP) photonic crystal (PC) with alternating in-plane lamellae, of which a variety of 3D and 2D perovskite nanocrystals is preferentially self-assembled with characteristic PL, is presented. The SC of a BCP PC is controlled in the visible range with different perovskite precursor doping times. The perovskite nanocrystals developed in the BCP PC are highly luminescent, with a PL quantum yield of ≈33.7%, yielding environmentally stable SC and PL dual-mode displays. The independently programmed SC and PL information is erasable and rewritable. Dual-responsive optical encryption is demonstrated, in which true Morse code information is deciphered only when the information encoded by SCs is properly combined with PL information. Numerous combinations of SC and PL realize high security level of data anticounterfeiting. This dual-mode encryption display offers novel optical encryption with high information security and anti-counterfeiting.

6.
Light Sci Appl ; 12(1): 226, 2023 Sep 12.
Article in English | MEDLINE | ID: mdl-37696793

ABSTRACT

Optical encryption technologies based on room-temperature light-emitting materials are of considerable interest. Herein, we present three-dimensional (3D) printable dual-light-emitting materials for high-performance optical pattern encryption. These are based on fluorescent perovskite nanocrystals (NCs) embedded in metal-organic frameworks (MOFs) designed for phosphorescent host-guest interactions. Notably, perovskite-containing MOFs emit a highly efficient blue phosphorescence, and perovskite NCs embedded in the MOFs emit characteristic green or red fluorescence under ultraviolet (UV) irradiation. Such dual-light-emitting MOFs with independent fluorescence and phosphorescence emissions are employed in pochoir pattern encryption, wherein actual information with transient phosphorescence is efficiently concealed behind fake information with fluorescence under UV exposure. Moreover, a 3D cubic skeleton is developed with the dual-light-emitting MOF powder dispersed in 3D-printable polymer filaments for 3D dual-pattern encryption. This article outlines a universal principle for developing MOF-based room-temperature multi-light-emitting materials and a strategy for multidimensional information encryption with enhanced capacity and security.

7.
Small ; 19(47): e2300568, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37518679

ABSTRACT

Despite the remarkable advances made in the development of 2D perovskites suitable for various high-performance devices, the development of sub-30 nm nanopatterns of 2D perovskites with anisotropic photoelectronic properties remains challenging. Herein, a simple but robust route for fabricating sub-30 nm 1D nanopatterns of 2D perovskites over a large area is presented. This method is based on nanoimprinting a thin precursor film of a 2D perovskite with a topographically pre-patterned hard poly(dimethylsiloxane) mold replicated from a block copolymer nanopattern consisting of guided self-assembled monolayered in-plane cylinders. 1D nanopatterns of various 2D perovskites (A'2 MAn -1 Pbn X3 n +1 ,A' = BA, PEA, X = Br, I) are developed; their enhanced photoluminescence (PL) quantum yields are approximately four times greater than those of the corresponding control flat films. Anisotropic photocurrent is observed because 2D perovskite nanocrystals are embedded in a topological 1D nanopattern. Furthermore, this 1D metal-coated nanopattern of a 2D perovskite is employed as a color conversion optical polarizer, in which polarized PL is developed. This is due to its capability of polarization of an incident light arising from the sub-30 nm line pattern, as well as the PL of the confined 2D perovskite nanocrystals in the pattern.

8.
Pharmaceutics ; 15(5)2023 May 21.
Article in English | MEDLINE | ID: mdl-37242798

ABSTRACT

Novel biocompatible and efficient photothermal (PT) therapeutic materials for cancer treatment have recently garnered significant attention, owing to their effective ablation of cancer cells, minimal invasiveness, quick recovery, and minimal damage to healthy cells. In this study, we designed and developed calcium ion-doped magnesium ferrite nanoparticles (Ca2+-doped MgFe2O4 NPs) as novel and effective PT therapeutic materials for cancer treatment, owing to their good biocompatibility, biosafety, high near-infrared (NIR) absorption, easy localization, short treatment period, remote controllability, high efficiency, and high specificity. The studied Ca2+-doped MgFe2O4 NPs exhibited a uniform spherical morphology with particle sizes of 14.24 ± 1.32 nm and a strong PT conversion efficiency (30.12%), making them promising for cancer photothermal therapy (PTT). In vitro experiments showed that Ca2+-doped MgFe2O4 NPs had no significant cytotoxic effects on non-laser-irradiated MDA-MB-231 cells, confirming that Ca2+-doped MgFe2O4 NPs exhibited high biocompatibility. More interestingly, Ca2+-doped MgFe2O4 NPs exhibited superior cytotoxicity to laser-irradiated MDA-MB-231 cells, inducing significant cell death. Our study proposes novel, safe, high-efficiency, and biocompatible PT therapeutics for treating cancers, opening new vistas for the future development of cancer PTT.

9.
ACS Nano ; 17(6): 5472-5485, 2023 Mar 28.
Article in English | MEDLINE | ID: mdl-36779414

ABSTRACT

Free-standing and film-type moisture-driven energy generators (MEGs) that harness the preferential interaction of ionized moisture with hydrophilic materials are interesting because of their wearability and portability without needing a water container. However, most such MEGs work in limited humidity conditions, which provide a substantial moisture gradient. Herein, we present a high-performance MEG with sustainable power-production capability in a wide range of environments. The bilayer-based device comprises a negatively surface-charged, hydrophilic MXene (Ti3C2Tx) aerogel and polyacrylamide (PAM) ionic hydrogel. The preferential selection on the MXene aerogel of positive charges supplied from the salts and water in the hydrogel is predicted by the first-principle simulation, which results in a high electric output in a wide relative humidity range from 20% to 95%. Furthermore, by replacing the hydrogel with an organohydrogel of PAM that has excellent water retention and structural stability, a device with long-term electricity generation is realized for more than 15 days in a broad temperature range (from -20 to 80 °C). Our MXene aerogel MEGs connected in series supply sufficient power for commercial electronic components in various outdoor environments. Moreover, an MXene aerogel MEG works as a self-powered sensor for recognizing finger bending and facial expression.

10.
J Adv Res ; 48: 87-104, 2023 06.
Article in English | MEDLINE | ID: mdl-36041689

ABSTRACT

Despite the many advanced strategies that are available, rapid gene mutation in multidrug-resistant bacterial infections remains a major challenge. Combining new therapeutic strategies such as chemo-photothermal therapy (PTT) with high antibacterial efficiency against drug-resistant Listeria monocytogenes (LM) is urgently needed. Here, we report synergistic chemo-PTT against drug-resistant LM based on antibody-conjugated and streptomycin-chitosan oligosaccharide-modified gold nanoshells (anti-STR-CO-GNSs) as all-in-one nanotheranostic agents for the first time, which was used for accurate antibacterial applications. The anti-STR-CO-GNSs showed excellent photothermal conversion efficiency (31.97 %) and were responsive to near-infrared (NIR) and pH dual stimuli-triggered antibiotic release, resulting in outstanding chemo-photothermal effects against LM. In vitro chemo-photothermal effect of anti-STR-CO-GNSs with laser irradiation caused a greater antibacterial effect (1.37 %), resulting in more rapid killing of LM and prevention of LM regrowth. Most importantly, the mice receiving the anti-STR-CO-GNSs with laser irradiation specifically at the sites of LM infections healed almost completely, leaving only scars on the surface of the skin and resulting in superior inhibitory effects from combined chemo-PTT. Overall, our findings suggest that chemo-PTT using smart biocompatible anti-STR-CO-GNSs is a favorable potential alternative to combat the increasing threat of drug-resistant LM, which opens a new door for clinical anti-infection therapy in the future.


Subject(s)
Bacterial Infections , Chitosan , Hyperthermia, Induced , Nanoshells , Animals , Mice , Photothermal Therapy , Phototherapy/methods , Streptomycin/pharmacology , Gold/pharmacology , Hyperthermia, Induced/methods , Anti-Bacterial Agents/pharmacology , Oligosaccharides
11.
Pharmaceutics ; 14(10)2022 Oct 20.
Article in English | MEDLINE | ID: mdl-36297675

ABSTRACT

Photo-nanotheranostics integrates near-infrared (NIR) light-triggered diagnostics and therapeutics, which are combined into a novel all-in-one phototheranostic nanomaterial that holds great promise for the early detection and precise treatment of cancer. In this study, we developed methylene blue-loaded mesoporous silica-coated gold nanorods on graphene oxide (MB-GNR@mSiO2-GO) as an all-in-one photo-nanotheranostic agent for intracellular surface-enhanced Raman scattering (SERS) imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer. Amine functionalization of the MB-GNR@mSiO2 surfaces was performed using 3-aminopropyltriethoxysilane (APTES), which was well anchored on the carboxyl groups of graphene oxide (GO) nanosheets uniformly, and showed a remarkably higher photothermal conversion efficiency (48.93%), resulting in outstanding PTT/PDT for cancer. The in vitro photothermal/photodynamic effect of MB-GNR@mSiO2-GO with laser irradiation showed significantly reduced cell viability (6.32%), indicating that MB-GNR@mSiO2-GO with laser irradiation induced significantly more cell deaths. Under laser irradiation, MB-GNR@mSiO2-GO showed a strong SERS effect, which permits accurate cancer cell detection by SERS imaging. Subsequently, the same Raman laser can focus on highly detected MDA-MB-23l cells for a prolonged time to perform PTT/PDT. Therefore, MB-GNR@mSiO2-GO has great potential for precise SERS imaging-guided synergistic PTT/PDT for cancer.

12.
ACS Nano ; 16(6): 9203-9213, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35588151

ABSTRACT

The development of electrodes with high conductivity, optical transparency, and reliable mechanical flexibility and stability is important for numerous solution-processed photoelectronic applications. Although transparent Ti3C2TX MXene electrodes with high conductivity are promising, their suitability for displays remains limited because of the high sheet resistance, which is caused by undesirable flake junctions and surface roughness. Herein, a flexible and transparent electrode has been fabricated that is suitable for a full-solution-processed quantum dot light-emitting diode (QLED). An MXene-silver nanowire (AgNW) hybrid electrode (MXAg) consists of a highly conductive AgNW network mixed with solution-processed MXene flakes. Efficient welding of wire-to-wire junctions with MXene flakes yields an electrode with a low sheet resistance and a high transparency of approximately 13.9 Ω sq-1 and 83.8%, respectively. By employing a thin polymer buffer layer of poly(methyl methacrylate) (PMMA), followed by mild thermal treatment, a hybrid PMMA-based MXene-AgNW (MXAg@PMMA) electrode in which the work function of an MXAg hybrid FTE physically embedded in PMMA (MXAg@PMMA) can be tuned by controlling the amount of MXene in the hybrid film facilitates the development of a high-performance solution-processed QLED that exhibits maximum external quantum and current efficiencies of approximately 9.88% and 25.8 cd/A, respectively, with excellent bending stability. This work function-tunable flexible transparent electrode based on solution-processed nanoconductors provides a way to develop emerging high-performance, wearable, cost-effective, and soft electroluminescent devices.

13.
Mater Today Bio ; 13: 100197, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35036895

ABSTRACT

Photothermal (PT)-enhanced Fenton-based chemodynamic therapy (CDT) has attracted a significant amount of research attention over the last five years as a highly effective, safe, and tumor-specific nanomedicine-based therapy. CDT is a new emerging nanocatalyst-based therapeutic strategy for the in situ treatment of tumors via the Fenton reaction or Fenton-like reaction, which has got fast progress in recent years because of its high specificity and activation by endogenous substances. A variety of multifunctional nanomaterials such as metal-, metal oxide-, and metal-sulfide-based nanocatalysts have been designed and constructed to trigger the in situ Fenton or Fenton-like reaction within the tumor microenvironment (TME) to generate highly cytotoxic hydroxyl radicals (•OH), which is highly efficient for the killing of tumor cells. However, research is still required to enhance the curative outcomes and minimize its side effects. Specifically, the therapeutic efficiency of certain CDTs is still hindered by the TME, including low levels of endogenous hydrogen peroxide (H2O2), overexpression of reduced glutathione (GSH), and low catalytic efficacy of Fenton or Fenton-like reactions (pH 5.6-6.8), which makes it difficult to completely cure cancer using monotherapy. For this reason, photothermal therapy (PTT) has been utilized in combination with CDT to enhance therapeutic efficacy. More interestingly, tumor heating during PTT not only causes damage to the tumor cells but can also accelerate the generation of •OH via the Fenton and Fenton-like reactions, thus enhancing the CDT efficacy, providing more effective cancer treatment when compared with monotherapy. Currently, synergistic PT-enhanced CDT using multifunctional nanomaterials with both PT and chemodynamic properties has made enormous progress in cancer theranostics. However, there has been no comprehensive review on this subject published to date. In this review, we first summarize the recent progress in PT-enhanced Fenton-based CDT for cancer treatment. We then discuss the potential and challenges in the future development of PT-enhanced Fenton-based nanocatalytic tumor therapy for clinical application.

14.
Small ; 18(6): e2106035, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34923744

ABSTRACT

Transition metal dichalcogenide (TMD) nanosheets exfoliated in the liquid phase are of significant interest owing to their potential for scalable and flexible photoelectronic applications. Although various dispersants such as surfactants, oligomers, and polymers are used to obtain highly exfoliated TMD nanosheets, most of them are electrically insulating and need to be removed; otherwise, the photoelectric properties of the TMD nanosheets degrade. Here, inorganic halide perovskite nanocrystals (NCs) of CsPbX3  (X = Cl, Br, or I) are presented as non-destructive dispersants capable of dispersing TMD nanosheets in the liquid phase and enhancing the photodetection properties of the nanosheets, thus eliminating the need to remove the dispersant. MoSe2 nanosheets dispersed in the liquid phase are adsorbed with CsPbCl3  NCs. The CsPbCl3 nanocrystals on MoSe2 efficiently withdraw electrons from the nanosheets, and suppress the dark current of the MoSe2 nanosheets, leading to flexible near-infrared MoSe2  photodetectors with a high ON/OFF photocurrent ratio and detectivity. Moreover, lanthanide ion-doped CsPbCl3  NCs enhance the ON/OFF current ratio to >106 . Meanwhile, the dispersion stability of the MoSe2  nanosheets exfoliated with the perovskite NCs is sufficiently high.

15.
ACS Nano ; 15(5): 8940-8952, 2021 May 25.
Article in English | MEDLINE | ID: mdl-33983015

ABSTRACT

MXenes (Ti3C2TX) are two-dimensional transition-metal carbides and carbonitrides with high conductivity and optical transparency. However, transparent MXene electrodes with high environmental stability suitable for various flexible organic electronic devices have rarely been demonstrated. By laminating a thin polymer film onto a solution-processed MXene layer to protect the MXene film from harsh environmental conditions, we present transparent and flexible MXene electronic devices. A thin polymer layer spin-coated onto a transparent MXene electrode provides environmental stability even under air exposure longer than 7 d at high temperatures (up to 70 °C) and humidity levels (up to 50%) without degrading the transparency of the electrode. The resulting polymer-laminated (PL) MXene electrode facilitates the development of a variety of field-driven photoelectronic devices by exploiting the electric field exerted between the MXene layer and the counter electrode through the insulating polymer. Field-induced electroluminescent displays, based on both organic and inorganic phosphors, with PL-MXene electrodes are demonstrated with high transparency and mechanical flexibility. Furthermore, our PL-MXene electrode exhibits high versatility through successful implementation in capacitive-type pressure sensors and triboelectric nanogenerators, resulting in field-driven sensing and energy harvesting electronic devices with excellent operation reliability.

16.
Front Genet ; 12: 658862, 2021.
Article in English | MEDLINE | ID: mdl-35173760

ABSTRACT

Macrophages exhibit high plasticity to achieve their roles in maintaining tissue homeostasis, innate immunity, tissue repair and regeneration. Therefore, macrophages are being evaluated for cell-based therapeutics against inflammatory disorders and cancer. To overcome the limitation related to expansion of primary macrophages and cell numbers, human pluripotent stem cell (hPSC)-derived macrophages are considered as an alternative source of primary macrophages for clinical application. However, the quality of hPSC-derived macrophages with respect to the biological homogeneity remains still unclear. We previously reported a technique to produce hPSC-derived macrophages referred to as iMACs, which is amenable for scale-up. In this study, we have evaluated the biological homogeneity of the iMACs using a transcriptome dataset of 6,230 iMACs obtained by single-cell RNA sequencing. The dataset provides a valuable genomic profile for understanding the molecular characteristics of hPSC-derived macrophage cells and provide a measurement of transcriptomic homogeneity. Our study highlights the usefulness of single cell RNA-seq data in quality control of the cell-based therapy products.

17.
J Mater Chem B ; 8(45): 10337-10345, 2020 12 07.
Article in English | MEDLINE | ID: mdl-33078175

ABSTRACT

The encapsulation of lead halide perovskite nanocrystals (PNCs) with an inert protective layer against moisture and the environment is a promising approach to overcome hinderances for their practical use in optoelectronic and biomedical applications. Herein, a facile method for synthesizing highly luminescent and biocompatible CsPbBr3@SiO2 core-shell PNCs with a controlled SiO2 thickness, which are suitable for both cell imaging and drug delivery, is reported. The synthesized CsPbBr3@SiO2 core-shell PNCs exhibit bright green emission at 518 nm upon excitation of 374 nm. Interestingly, a significant increase in the photoluminescence intensity is observed with an increase in the SiO2 shell thickness, which varies with the increasing reaction time. Cytotoxicity results indicate that the CsPbBr3@SiO2 core-shell PNCs are nontoxic, making them suitable for in vitro cell imaging using HeLa cells. Furthermore, doxorubicin physically adsorbed on the surface of CsPbBr3@SiO2 core-shell PNCs is efficiently released in cells when the drug-loaded perovskite nanoprobes are injected in the cells, indicating that these core-shell nanoparticles can be used for drug loading and delivery. The results of this study suggest that the CsPbBr3@SiO2 core-shell PNCs can pave the way for new biomedical applications and processes.


Subject(s)
Cesium/chemistry , Drug Carriers/chemistry , Lead/chemistry , Luminescent Agents/chemistry , Silicon Dioxide/chemistry , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacology , Calcium Compounds/chemistry , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Drug Delivery Systems , HeLa Cells , Humans , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Optical Imaging/methods , Oxides/chemistry , Titanium/chemistry
18.
Emerg Microbes Infect ; 9(1): 1943-1954, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32820712

ABSTRACT

Pluripotent stem cell-derived cerebral organoids have the potential to recapitulate the pathophysiology of in vivo human brain tissue, constituting a valuable resource for modelling brain disorders, including infectious diseases. Toxoplasma gondii, an intracellular protozoan parasite, infects most warm-blooded animals, including humans, causing toxoplasmosis. In immunodeficient patients and pregnant women, infection often results in severe central nervous system disease and fetal miscarriage. However, understanding the molecular pathophysiology of the disease has been challenging due to limited in vitro model systems. Here, we developed a new in vitro model system of T. gondii infection using human brain organoids. We observed that tachyzoites can infect human cerebral organoids and are transformed to bradyzoites and replicate in parasitophorous vacuoles to form cysts, indicating that the T. gondii asexual life cycle is efficiently simulated in the brain organoids. Transcriptomic analysis of T. gondii-infected organoids revealed the activation of the type I interferon immune response against infection. In addition, in brain organoids, T. gondii exhibited a changed transcriptome related to protozoan invasion and replication. This study shows cerebral organoids as physiologically relevant in vitro model systems useful for advancing the understanding of T. gondii infections and host interactions.


Subject(s)
Brain/parasitology , Interferon Type I/genetics , Organoids/parasitology , Toxoplasma/physiology , Animals , Brain/cytology , Brain/immunology , Cell Line , Disease Models, Animal , Gene Expression Profiling , Gene Regulatory Networks , High-Throughput Nucleotide Sequencing , Humans , Organ Culture Techniques , Organoids/cytology , Organoids/immunology , Toxoplasma/pathogenicity , Toxoplasmosis
19.
Adv Mater ; 32(30): e2000597, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32530144

ABSTRACT

Tremendous efforts have been devoted to developing thin film halide perovskites (HPs) for use in high-performance photoelectronic devices, including solar cells, displays, and photodetectors. Furthermore, structured HPs with periodic micro- or nanopatterns have recently attracted significant interest due to their potential to not only improve the efficiency of an individual device via the controlled arrangement of HP crystals into a confined geometry, but also to technologically pixelate the device into arrays suitable for future commercialization. However, micro- or nanopatterning of HPs is not usually compatible with conventional photolithography, which is detrimental to ionic HPs and requires special techniques. Herein, a comprehensive overview of the state-of-the-art technologies used to develop micro- and nanometer-scale HP patterns, with an emphasis on their controlled microstructures based on top-down and bottom-up approaches, and their potential for future applications, is provided. Top-down approaches include modified conventional lithographic techniques and soft-lithographic methods, while bottom-up approaches include template-assisted patterning of HPs based on lithographically defined prepatterns and self-assembly. HP patterning is shown here to not only improve device performance, but also to reveal the unprecedented functionality of HPs, leading to new research areas that utilize their novel photophysical properties.

20.
Stem Cell Res ; 45: 101735, 2020 05.
Article in English | MEDLINE | ID: mdl-32268246

ABSTRACT

Toll-like receptor 7 (TLR7) is a member of the toll-like receptor (TLR) family that is essential in the innate immune system. In this study, we established a heterozygous TLR7 knockout H9 cell line using CRISPR/Cas9. TLR7 knockout H9 cells maintained their pluripotency and exhibited the ability to differentiate into the three germ layers without any karyotype abnormalities.


Subject(s)
Human Embryonic Stem Cells , CRISPR-Cas Systems/genetics , Cell Line , Heterozygote , Humans , Toll-Like Receptor 7/genetics
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