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High-order correlated excitonic states, such as biexciton, charged biexciton, and polaron, hold a promising platform in contemporary quantum and nonlinear optics due to their large Bohr radii and thus strong nonlinear interactions. The recently found 2D TMDs further give such excitonic states additional valley properties, with bound state of excitons in opposite valleys in momentum spaces. Despite great efforts that have been made on emission properties of excitonic states, their absorption features, especially the ultrafast absorption dynamics, are rarely reported. Here, we reported the enhanced optical absorption of the high-order charged-excitonic states in monolayer WS2, including singlet, triplet, and semidark trions (3-particle state), and charged biexcitons (5-particle state), by utilizing the interlayer charge transfer-induced photo-doping effect in the graphene-WS2 heterostructure. Depending on recombination rates of doping electrons, absorption intensities of charged complexes exhibit ultrafast decay dynamics, with lifetimes of several picoseconds. Due to many-body interaction, both increasing pump intensity and lattice temperature can broaden these fine excitonic absorption peaks and even reverse the shape of the transient absorption spectrum.
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For covert communication in lossy channels, it is necessary to consider that the carrier of the hidden watermark will undergo multiple image-processing attacks. In order to ensure that secret information can be extracted without distortion from the watermarked images that have undergone attacks, in this paper, we design a novel fragmented secure communication system. The sender will fragment the secret data to be transmitted and redundantly hide it in a large number of multimodal carriers of messenger accounts on multiple social platforms. The receiver receives enough covert carriers, extracts each fragment, and concatenates the transmitted secret data. This article uses the image carrier as an example to fragment the text file intended for transmission and embeds it into a large number of images, with each fragment being redundant and embedded into multiple images. In this way, at the receiving end, only enough stego images need to be received to extract the information in each image, and then concatenate the final secret file. In order to resist various possible attacks during image transmission, we propose a strong robust image watermarking method. This method adopts a watermark layer based on DFT, which has high embedding and detection efficiency and good invisibility. Secondly, a watermark layer based on DCT is adopted, which can resist translation attacks, JPEG attacks, and other common attacks. Experiments have shown that our watermarking method is very fast; both the embedding time and the extraction time are less than 0.15 s for images not larger than 2000×2000. Our watermarking method has very good invisibility with 41dB PSNR on average. And our watermarking method is more robust than existing schemes and robust to nearly all kinds of attacks. Based on this strong robust image watermarking method, the scheme of fragmenting and hiding redundant transmission content into a large number of images is effective and practical. Our scheme can 100% restore the secret file completely under different RST or hybrid attacks, such as rotation by 1 degree and 5 degrees, scaling by 1.25 and 0.8, and cropping by 10% and 25%. Our scheme can successfully restore the secret file completely even if 30% of received images are lost. When 80% of received images are lost, our scheme can still restore 61.1% of the secret file. If all stego images can be obtained, the original text file can be completely restored.
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Foxtail millet (Setaria italica), a vital drought-resistant crop, plays a significant role in ensuring food and nutritional security. However, its drought resistance mechanism is not fully understood. N6 -methyladenosine (m6 A) modification of RNA, a prevalent epi-transcriptomic modification in eukaryotes, provides a binding site for m6 A readers and affects plant growth and stress responses by regulating RNA metabolism. In this study, we unveiled that the YT521-B homology (YTH) family gene SiYTH1 positively regulated the drought tolerance of foxtail millet. Notably, the siyth1 mutant exhibited reduced stomatal closure and augmented accumulation of excessive H2 O2 under drought stress. Further investigations demonstrated that SiYTH1 positively regulated the transcripts harboring m6 A modification related to stomatal closure and reactive oxygen species (ROS) scavenging under drought stress. SiYTH1 was uniformly distributed in the cytoplasm of SiYTH1-GFP transgenic foxtail millet. It formed dynamic liquid-like SiYTH1 cytosol condensates in response to drought stress. Moreover, the cytoplasmic protein SiYTH1 was identified as a distinct m6 A reader, facilitating the stabilization of its directly bound SiARDP and ROS scavenging-related transcripts under drought stress. Furthermore, natural variation analysis revealed SiYTH1AGTG as the dominant allele responsible for drought tolerance in foxtail millet. Collectively, this study provides novel insights into the intricate mechanism of m6 A reader-mediated drought tolerance and presents a valuable genetic resource for improving drought tolerance in foxtail millet breeding.
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Resistencia a la Sequía , Setaria (Planta) , Especies Reactivas de Oxígeno/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Setaria (Planta)/metabolismo , Proteínas de Plantas/metabolismo , Fitomejoramiento , Regulación de la Expresión Génica de las Plantas/genética , Estrés Fisiológico/genéticaRESUMEN
Integrating metal halide perovskites onto plasmonic nanostructures has recently become a trending method of enabling superior emissive performance of perovskite nanophotonic devices. In this work, we present an in-depth study on the spontaneous emission properties of hybrid systems comprising CsPbBr3 nanocrystals and silver nanostructures. Specifically, a 5.7-fold increment of the photoluminescence (PL) intensity and a 1.65-fold enhancement of the PL relaxation rate is attained when the transition energy of CsPbBr3 is spectrally resonant with the oscillational frequency of Ag nanodisks (NDs), which is attributed to the intense exciton-plasmon coupling-induced Purcell effect. Furthermore, a 540-fs ultrafast energy transfer from the CsPbBr3 excitons to Ag plasmons is revealed by femtosecond pump-probe experiments, suggesting the key mechanism responsible for the Purcell-enhanced radiative emission. Our finding offers a unique understanding of the enhanced emissive behavior in the plasmon-coupled perovskite system and paves the way for further applications.
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Chronic elevated free fatty acids (FFAs) impair pancreatic ß cells, but the mechanisms remain elusive. In this study, palmitic acid (PA) impaired viability and glucose-stimulated insulin secretion of INS-1 cells. Microarray analysis showed that PA markedly altered the expression of 277 probe sets of genes with 232 upregulated and 45 downregulated (fold change ≥ 2.0 or ≤ -2.0; P < 0.05). Gene Ontology analysis displayed a series of the biological process of the differentially expressed genes, such as intrinsic apoptotic signaling pathway in response to endoplasmic reticulum (ER) stress and oxidative stress, inflammatory response, positive regulation of macroautophagy, regulation of insulin secretion, cell proliferation and cycle, fatty acid metabolic process, glucose metabolic process and so on. Kyoto Encyclopedia of Genes and Genomes analysis demonstrated molecular pathways with which the differentially expressed genes associated, including NOD-like receptor, NF-κB and PI3K-Akt signaling pathways, apoptosis, adipocytokine signaling pathway, ferroptosis, protein processing in ER, fatty acid biosynthesis and cell cycle. Moreover, PA promoted protein expression of CHOP, cleaved caspase-3, microtubule-associated proteins light chain 3 (LC3)-II, NOD-like receptor pyrin domain containing 3 (NLRP3), cleaved IL-1ß and Lcn2, increased reactive oxygen species, apoptosis and the ratio of LC3-II/I, and reduced p62 protein expression, intracellular glutathione peroxidase and catalase levels, suggesting activation of ER stress, oxidative stress, autophagy and NLRP3 inflammasome. The results indicate the impaired role of PA and the global gene expression profile of INS-1 cells following PA intervention, providing new insights into the mechanisms involving the damage of pancreatic ß cells by FFAs.
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Proteína con Dominio Pirina 3 de la Familia NLR , Ácido Palmítico , Apoptosis/genética , Estrés del Retículo Endoplásmico/genética , Glucosa , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Fosfatidilinositol 3-Quinasas/metabolismo , TranscriptomaRESUMEN
In this work, we experimentally study the nonlinear absorption enhancement of saturable absorption and two-photon absorption on a hybrid structure comprising a monolayer MoS2 and Au nanoantennas via femtosecond I-scan measurement. Specifically, a 13-fold increment in the linear absorption coefficient is attained at 1.85 eV, along with an 8-fold enhancement of the two-photon absorption coefficient at 1.65 eV, which is attributed to exciton-plasmon coupling resonance and plasmonic hot electron transfer. The exciton-plasmon coupling effect is characterized by stable photoluminescence experiments. Furthermore, the exciton recombination time is extracted from the pump-probe measurement, whose value in the hybrid structure is shortened from 18.5 ps (pure MoS2) to 1.84 ps. Our findings facilitate a new perspective to modulate the nonlinear optical response and to promote the performance of nonlinear photonic devices.
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Recently, topological insulator based heterostructures (HSs) have attracted tremendous research interest, due to their efficient carrier transfer features at the heterointerface induced by metallic surface states. Here, a novel HS comprising 0D perovskite CsPbBr3 quantum dots (QDs) and 2D material topological insulator Bi2Se3 film is proposed and experimentally investigated. Specifically, steady state and time-resolved photoluminescence (PL) measurements are employed, from which a significant quenching behaviour is observed in the HS, with an average quenching factor of 93.2 ± 0.8%. Additionally, time-resolved PL spectroscopy affirms that the carrier transfer efficiency can be up to 92.6 ± 0.2%. Furthermore, the dynamics of carrier transfer within the 0D-2D HS are characterized by utilizing femtosecond broadband transient absorption (TA) spectroscopy, revealing an ultrafast exciton transfer from photoexcited CsPbBr3 QDs to the Bi2Se3 film with a time-scale around 1.1 ± 0.2 ps. An alternative important finding is that the band renormalization is exhibited in CsPbBr3 QDs of the HS, with the dominant factor being the Coulomb screening effect. This work is expected to provide some fundamental understanding of the ultrafast and efficient carrier transfer mechanism underneath HSs based on topological insulators.
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In this work, we present an in-depth study on a low-dimensional heterostructure comprising monolayer (ML) tungsten disulfide (WS2) and 1D plasmonic photonic crystal (PPC). Stable-state photoluminescence (PL) experiments are employed to study the optical properties of WS2 films with and without PPC. In addition, angle-resolved reflectance and PL microscopy measurements are used to identify the coupling effects between ML WS2 and 1D PPC. Furthermore, by means of femtosecond pump-probe experiments, the relaxation time for the newly proposed heterostructure is extracted to be 0.74 ps and 21.9 ps. Importantly, the underlying mechanism of the relaxation processes is also revealed in the hybrid for the first time, to the best of our knowledge.
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OBJECTIVE: To evaluate the therapeutic effects of pulpotomy and pulpectomy on deciduous molars with deep caries. METHODS: A total of 124 children (192 molars) with deep caries treated from February 2014 to February 2015 were selected. They each had at least one molar with deep caries. MTA pulpotomy (101 molars) and Vitapex pulpectomy (91 molars) as well as prefabricated metal crown repair were conducted. The patients were followed up for 18 months after surgery, and the therapeutic effects were evaluated through clinical and X-ray examinations. RESULTS: The proportion of molars without lesions was 80.20% in pulpotomy group, which significantly exceeded that of pulpectomy group (72.53%). The pulpotomy group with good clinical manifestations underwent spontaneous pain in four molars during follow-up, and five molars gradually underwent pain and gingival redness and swelling. The pulpectomy group suffered from occlusion discomfort in nine molars and gingival fistula in seven molars during follow-up. The postoperative morbidity of pulpectomy group was significantly higher than that of pulpotomy group (χ2=4.50, P=0.04). The 18-month tooth survival rates of pulpotomy and pulpectomy groups were 90% and 79% respectively, which were significantly different (χ2=4.645, P=0.031). CONCLUSION: The postoperative outcomes of pulpotomy are superior to those of pulpectomy.
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BACKGROUND: Polycystic ovarian syndrome (PCOS) is a complicated endocrine and metabolic disease, which seriously affects women's health. However, the etiology and genetic basis of PCOS are complex, and the pathogenesis remains unclear. In this study, we aimed to explore the effects of clomiphene and dexamethasone on PCOS and their potential mechanisms. METHODS: Sprague-Dawley (SD) rats were injected with dehydroepiandrosterone (DHEA) to establish a PCOS model. After treatment with clomiphene, dexamethasone, and their combination, ovarian tissue of rats was collected. The morphological changes in the ovary were observed by hematoxylin and eosin (HE) staining and Electron microscopy. The levels of oxidative stress and hormones were determined by ELISA. Apoptosis was assessed by TUNEL assay. The mechanism of clomiphene and dexamethasone effects on PCOS was explored by Immunohistochemical staining, real-time PCR, and western blotting. RESULTS: Clomiphene and dexamethasone could improve the morphology of the ovary in PCOS. TUNEL assay and ELISA showed that clomiphene, dexamethasone, and their combination could inhibit apoptosis and significantly reverse the levels of ROS, T-SOD, CAT, T, and E2 in the ovary. Immunohistochemical staining revealed that clomiphene and dexamethasone could remarkably reduce the protein levels of Bax, Caspase-3, LC3II, p-JNK, p-P38 MAPK, and P21, and increase P62 and Bcl-2 protein expression. The mRNA levels of Bax, Bcl-2, and Caspase-3 were also modulated in the PCOS model with clomiphene and dexamethasone treatment. Additionally, western blotting indicated that clomiphene and dexamethasone significantly regulated the levels of Bax, Bcl-2, Caspase-3, LC3I, LC3II, P62, p-JNK, JNK, p-P38 MAPK, P38 MAPK, and P21 in PCOS rats. CONCLUSIONS: Clomiphene and dexamethasone can not only reduce oxidative damage, and inhibit apoptosis and autophagy, but they can also regulate the ROS-JNK/MAPK-P21 signaling pathway in PCOS rats. It provides an experimental basis for the clinical application of clomiphene and dexamethasone in PCOS.
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New indocyanine green (ICG) (IR820) is one of the ICG derivatives and attracts increasing attention for cancer management. However, the unsatisfactory tumor targeting ability of IR820 significantly limits its applications for cancer theranostics. Biotin receptor is overexpressed on the membrane of various tumor cells and biotin modified nanocarriers have been reported to enhance the tumor targeting ability on several tumor types. In this work, biotin-new ICG conjugate (Biotin-SS-IR820) was prepared for tumor-targeted IR820 delivery. Biotin and IR820 were coupled through cystamine. The synthesized Biotin-SS-IR820 was characterized by 1 H NMR, FT-IR and HRMS. The in vitro singlet oxygen generation study shows that Biotin-SS-IR820 exhibits similar singlet oxygen generation as compared to IR820 upon 660 nm laser irradiation (0.8 W/cm2 ). The cellular uptake study shows that Biotin-SS-IR820 shows enhanced cellular uptake amount as compared to IR820 on 4T1 cells. As a result, Biotin-SS-IR820 displays enhanced in vitro photodynamic therapeutic effect against 4T1 cells as compared to IR820. In in vivo biodistribution study, Biotin-SS-IR820 shows enhanced tumor accumulation as compared to IR820. Biotin-SS-IR820 developed in this work shows promising prospects for targeted delivery of IR820 to biotin receptor overexpressed tumors.
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Biotina , Neoplasias , Humanos , Verde de Indocianina , Distribución Tisular , Oxígeno Singlete , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
INTRODUCTION: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, TNBC tumor cells are girdled by stroma composed of cancer-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. OBJECTIVES: Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition, and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, and increase tumor perfusion. The nanodrug delivery system co-encapsulating FX and nucleic acid drug Twist siRNA (siTwist) was expected to form a potent anti-TNBC therapeutic cyclical feedback loop. METHODS AND RESULTS: Herein, our studies constituted a novel self-assembled polymer nanomedicine (siTwist/FX@HES-CH) based on the amino-modified hydroxyethyl starch (HES-NH2) grafted with hydrophobic segment cholesterol (CH). The MTT assay, flow cytometry apoptosis analysis, transwell assay, western blot, and 3D multicellular tumor spheroids growth inhibition assay all showed that siTwist/FX@HES-CH could kill tumor cells and inhibit their metastasis in a synergistic manner. The in vivo anti-TNBC efficacy was demonstrated that siTwist/FX@HES-CH remodeled tumor microenvironment, facilitated interstitial barrier crossing, killed tumor cells synergistically, drastically reduced TNBC orthotopic tumor burden and inhibited lung metastasis. CONCLUSION: Systematic studies revealed that this dual-functional nanomedicine that targets both tumor cells and tumor microenvironment significantly alleviates TNBC orthotopic tumor burden and inhibits lung metastasis, establishing a new paradigm for TNBC therapy.
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Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy.
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Portadores de Fármacos , Derivados de Hidroxietil Almidón , Verde de Indocianina , Nanopartículas , Verde de Indocianina/química , Verde de Indocianina/farmacología , Animales , Nanopartículas/química , Ratones , Portadores de Fármacos/química , Línea Celular Tumoral , Derivados de Hidroxietil Almidón/química , Derivados de Hidroxietil Almidón/farmacología , Vincristina/farmacología , Vincristina/química , HumanosRESUMEN
BACKGROUND: Identification of active components of traditional Chinese Medicine (TCM) and their respective targets is important for understanding the mechanisms underlying TCM efficacy. However, there are still no effective technical methods to achieve this. METHODS: Herein, we have established a method for rapidly identifying targets of a specific TCM and interrogating the targets with their corresponding active components based on Isothermal Shift Assay (iTSA) and database interrogation. RESULTS: We optimized iTSA workflow and identified 110 targets for Danhong injection (DHI) which is used as an effective remedy for cardiovascular and cerebrovascular diseases. Moreover, we identified the targets of the nine major ingredients found in DHI. Database interrogation found that the potential targets for DHI, in which we verified that ADK as the target for salvianolic acid A and ALDH1B1 as the target for protocatechualdehyde in DHI, respectively. CONCLUSION: Overall, we established a novel paradigm model for the identification of targets and their respective ingredients in DHI, which facilitates the discovery of drug candidates and targets for improving disease management and contributes to revealing the underlying mechanisms of TCM and fostering TCM development and modernization.
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OBJECTIVE: The objective of this work was to prepare coenzyme Q10 loaded nanostructured lipid carriers (Q10-NLC) and evaluate its epidermal targeting effect. METHODS: Q10-NLC was prepared by high-pressure microfluidics technique. Formulations and preparation parameters were optimized with response surface design. Q10-NLC was characterized by PCS, TEM, DSC and PXRD. The penetration of Q10 from the Q10-NLC formulations through skins and into skins were evaluated in vitro using Franz diffusion cells fitted with SD rat skins. In vitro release, long-term stability and light stability were also evaluated. RESULTS: The results showed that the concentration of solid lipid and emulsifier in formulation had a significant influence on particle size. The optimized preparation parameters were magnetic stirring for 20 min, high stirring at 8000 rpm for 1 min and high-pressure microfluidics at 1200 bar for three cycles. The size of Q10-NLC prepared by optimized formulation and parameters was (151.7 ± 2.31) nm, polydispersity (PDI) 0.144, ζ potential was (-44.1 ± 1.68) mV, drug loading 2.51%, encapsulation efficiency 100%. In vitro release study, Q10-NLC showed fast release during the first 3 hours and prolonged release afterwards. In vitro skin permeation study, the accumulative uptake of Q10 in epidermal of Q10-NLC was 10.11 times over Q10 emulsion. After exposure to day light for 24 hours, the amount of Q10 in Q10-NLC decreased only 5.59%, while in Q10 emulsion decreased 24.61% and Q10-ethanol solution 49.74%. CONCLUSION: Q10-NLC exhibited a significant epidermal targeting effect, which was proved to be a promising carrier for topical delivery of Q10.
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Portadores de Fármacos , Nanopartículas/administración & dosificación , Ubiquinona/análogos & derivados , Administración Tópica , Animales , Epidermis , Lípidos/administración & dosificación , Lípidos/química , Microfluídica/métodos , Nanopartículas/química , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Absorción Cutánea/efectos de los fármacos , Ubiquinona/administración & dosificación , Ubiquinona/químicaRESUMEN
Objectives: This study aimed to systematically review the effectiveness of service interventions for improving postpartum contraception, including contraceptive use, prevention of repeat pregnancies and induced abortions. Methods: A systematic literature search was conducted in three databases until June 2022 (PROSPERO registration CRD42022328349). Estimates of intervention effects from meta-analyses were represented as odds ratios (OR) with 95% confidence intervals (CI). Results: 16 studies with 14,289 participants were included, with four kinds of interventions recognized. Interventions effect in increasing use of contraceptives and decreasing rates of repeated pregnancy for up to 6 months postpartum (OR = 2.24, 0.06, 95% CI = 1.46-3.44, 0.02-0.22, respectively), with no significant associations with contraceptive use at 12 months postpartum, prevention of postpartum repeat pregnancies and induced abortions during 1 year after childbirth. Conclusion: We concluded that interventions impact the initiation of postpartum contraceptive use and prevention of repeat pregnancy with an overall certainty from low to moderate. These findings highlight the need for additional studies to integrate the beneficial effect of several interventions and then design more feasible strategies, which is important for the maternal and child healthcare systems.
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Aborto Inducido , Servicios de Salud Materna , Embarazo , Femenino , Niño , Humanos , Anticoncepción , Periodo Posparto , AnticonceptivosRESUMEN
TGF-ß is widely existed in tumor microenvironment, taking part in tumorigenesis process including angiogenesis, cancer associated fibroblast (CAF) proliferation, and immunosuppression. It inhibited the activation, proliferation, migration and differentiation of T cells, in which way caused a limited therapeutic effects of chimeric antigen receptor T (CAR-T) towards solid tumor such as lymphoma. To targeted block TGF-ß at tumor site, we take advantages of nano-techniques to deliver TGF-ß inhibitors LY2157299 (LY) towards the tumor sites, in order to help achieve a improved and long-term functions of CAR-T towards lymphoma. Based on amphipathic hydroxyethyl starch-polycaprolactone (HES-PCL), LY and photosensitizer indocyanine green (ICG) were co-loaded in HES-PCL to achieve LY/ICG@HES-PCL nanoparticle. The enhanced function of CAR-T benefited from LY/ICG@HES-PCL were verified through lymphoma Raji cells in vitro and Nod scid gamma mice engrafted with the Raji cells in vivo. LY was targeted transported to tumor site and accelerated release by mild ICG photothermal. Chemokines CXCL9/10/11 âat the tumor site relevant to CAR-T migration and chemokines receptor CXCR3 of CAR-T could be up-regulated by LY, thus facilitated the enhanced accumulation of CAR-T at lymphoma site. T effector memory cells differentiation could also be accelerated by LY/ICG@HES-PCL. Combined therapy of LY/ICG@HES-PCL and CAR-T achieved 2.4 times higher antitumor activity and 2.7 times higher relapse inhibiting rates than CAR-T alone within 15 days and 11 days, respectively. The results suggested that LY/ICG@HES-PCL facilitated the enhanced therapeutic index of CAR-T cells towards lymphoma simply and safely, it may be further potentiated applied for other solid tumors.
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Controlling the interaction between light and matter at micro- and nano-scale can provide new opportunities for modern optics and optoelectronics. An archetypical example is polariton, a half-light-half-matter quasi particle inheriting simultaneously the robust coherence of light and the strong interaction of matter, which plays an important role in many exotic phenomena. Here, we open up a new kind of cooperative coupling between plasmon and different excitonic complexes in WS2-silver nanocavities, namely plasmon-exciton-trion-charged biexciton four coupling states. Thanks to the large Bohr radius of up to 5 nm, the charged biexciton polariton exhibits strong saturation nonlinearity, ~30 times higher than the neutral exciton polariton. Transient absorption dynamics further reveal the ultrafast many-body interaction nature, with a timescale of <100 fs. The demonstration of biexciton polariton here combines high nonlinearity, simple processing and strong scalability, permitting access for future energy-efficient optical switching and information processing.
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Chemo-photodynamic therapy shows great potential for cancer treatment. However, the rational integration of chemotherapeutic agents and photosensitizers to construct an intelligent nanoplatform with synergistic therapeutic effect is still a great challenge. In this work, curcumin-loaded reduction-responsive prodrug nanoparticles of new indocyanine green (Cur@IR820-ss-PEG) were developed for synergistic cancer chemo-photodynamic therapy. Cur@IR820-ss-PEG exhibit high drug loading content and special worm-like morphology, contributing to their efficient cellular uptake. Due to the presence of the disulfide bond between IR820 and PEG, Cur@IR820-ss-PEG display reduction responsive drug release behaviors. The efficient cellular uptake and reduction triggered drug release of Cur@IR820-ss-PEG lead to their enhanced in vitro cytotoxicity against 4T1cells as compared to the mixture of IR820 and curcumin (IR820/Cur) under laser irradiation. Besides, Cur@IR820-ss-PEG exhibit prolonged blood half-life time, better tumor accumulation and retention, enhanced tumor hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) suppression effect as compared to IR820/Cur. In vivo antitumor activity study, Cur@IR820-ss-PEG effectively inhibit the tumor angiogenesis, which potentiates the PDT efficacy and leads to the best in vivo antitumor effect of Cur@IR820-ss-PEG. This work provides a novel and relatively simple strategy for synergistic cancer chemo-photodynamic therapy.
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Chimeric antigen receptor (CAR) T cells exhibit promising progress in addressing hematologic malignancies. However, CAR-T therapy for solid tumors remains limited, with no FDA-approved CAR-T products available for clinical use at present. Primary reasons include insufficient infiltration, accumulation, tumor immunosuppression of the microenvironment, and related side effects. Single utilization of CAR-T cannot effectively overcome these unfavorable obstacles. A probable effective pathway to achieve a better CAR-T therapy effect would be to combine the benefits of biomaterials-based technology. In this article, comprehensive biomaterials strategies to break through these obstacles of CAR-T cell therapy at the tumor sites are summarized, encompassing the following aspects: 1) generating orthotopic CAR-T cells; 2) facilitating CAR-T cell trafficking; 3) stimulating CAR-T cell expansion and infiltration; 4) improving CAR-T cell activity and persistence; 5) reprogramming the immunosuppressive microenvironments. Additionally, future requirements for the development of this field, with a specific emphasis on promoting innovation and facilitating clinical translation, are thoroughly discussed.