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Thrombus causes a serious condition characterized by the formation of blood clots in blood vessels or heart, potentially leading to life-threatening emergencies. Photothermal therapy (PTT) serves as a treatment for thrombosis that provides noninvasive thrombus dissolution and fewer bleeding side effects. However, the high temperatures generated by PTT can exacerbate vascular inflammation and promote thrombus recurrence. In this study, a photothermal hydrogen sulfide (H2S) nanogenerator (PSA@ADT-OH) is constructed using a perylene-cored photothermal agent (PSA) coassembled with a H2S donor ADT-OH. The system PSA@ADT-OH demonstrates outstanding targeting and accumulation efficiency against blood flow shear forces. It also provides sustained H2S release at thrombus sites, contributing to antiplatelet aggregation, reactive oxygen species clearance, and vascular healing. This approach opens up new possibilities for advanced thrombus treatment.
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Plant Growth Regulators (PGRs) are functional compounds known for enhancing plant growth and development. However, their environmental impact is a concern due to poor water solubility and the need for substantial organic solvents. Recently, nano-delivery systems have emerged as a solution, offering a broad range of applications for small molecule compounds. This study introduces a nano-delivery system for Triacontanol (TA), utilizing a star polymer (SPc), aimed at promoting maize growth and improving physiological indicators. The system forms nearly spherical nanoparticles through TA's hydroxyl group and SPc's tertiary amine group. The TA/SPc nano-complex notably outperforms separate TA or SPc treatments in maize, increasing biomass, chlorophyll content, and nutrient absorption. It elevates chlorophyll content by 16.4%, 10.0%, and 6.2% over water, TA, and SPc treatments, respectively, and boosts potassium and nitrate ion uptake by up to 2 and 1.6 times compared to TA alone, leading to enhanced plant height and leaf growth. qRT-PCR analysis further demonstrated that the nano-complex enhanced cellular uptake through the endocytosis pathway by up-regulating endocytosis-related gene expression. The employment of TEM to observe vesicle formation during the internalization of maize leaves furnishes corroborative evidence for the participation of the endocytosis pathway in this process. This research confirms that SPc is an effective carrier for TA, significantly enhancing biological activity and reducing TA dosage requirements.
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Alcoholes Grasos , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/efectos de los fármacos , Zea mays/metabolismo , Alcoholes Grasos/farmacología , Nanopartículas/química , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/metabolismo , Polímeros/química , Polímeros/farmacología , Clorofila/metabolismoRESUMEN
Photothermal therapy (PTT) represents a groundbreaking approach to targeted disease treatment by harnessing the conversion of light into heat. The efficacy of PTT heavily relies on the capabilities of photothermal agents (PTAs). Among PTAs, those based on organic dyes exhibit notable characteristics such as adjustable light absorption wavelengths, high extinction coefficients, and high compatibility in biological systems. However, a challenge associated with organic dye-based PTAs lies in their efficiency in converting light into heat while maintaining stability. Manipulating dye aggregation is a key aspect in modulating non-radiative decay pathways, aiming to augment heat generation. This review delves into various strategies aimed at improving photothermal performance through constructing aggregation. These strategies including protecting dyes from photodegradation, inhibiting non-photothermal pathways, maintaining space within molecular aggregates, and introducing intermolecular photophysical processes. Overall, this review highlights the precision-driven assembly of organic dyes as a promising frontier in enhancing PTT-related applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.
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Colorantes , Terapia Fototérmica , Humanos , Colorantes/química , Animales , Ratones , Neoplasias/terapiaRESUMEN
Reactive oxygen species (ROS) have become an effective tool for tumor treatment. The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) takes advantage of various ROS and enhances therapeutic effects. However, the activation of CDT usually occurs before PDT, which hinders the sustained maintenance of hydroxyl radicals (â OH) and reduces the treatment efficiency. Herein, we present a light-triggered nano-system based on molecular aggregation regulation for converting cancer therapy from PDT/photothermal therapy (PTT) to a long-lasting CDT. The ordered J-aggregation enhances the photodynamic properties of the cyanine moiety while simultaneously suppressing the chemodynamic capabilities of the copper-porphyrin moiety. Upon light irradiation, Cu-PCy JNPs demonstrate strong photodynamic and photothermal effects. Meanwhile, light triggers a rapid degradation of the cyanine backbone, leading to the destruction of the J-aggregation. As a result, a long-lasting CDT is sequentially activated, and the sustained generation of â OH is observed for up to 48â hours, causing potent cellular oxidative stress and apoptosis. Due to their excellent tumor accumulation, Cu-PCy JNPs exhibit effective in vivo tumor ablation through the converting therapy. This work provides a new approach for effectively prolonging the chemodynamic activity in ROS-based cancer therapy.
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Fotoquimioterapia , Fármacos Fotosensibilizantes , Terapia Fototérmica , Animales , Humanos , Ratones , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Cobre/química , Cobre/farmacología , Luz , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia , Carbocianinas/química , Carbocianinas/farmacología , Supervivencia Celular/efectos de los fármacosRESUMEN
The improper use of synthetic pesticides has caused adverse effects on global ecosystems and human health. As a part of sustainable pest management strategy, natural predators, along with nano-pesticides, have made significant contributions to ecological agriculture. The cooperative application of both approaches may overcome their limitations, substantially reducing pesticide application while controlling insect pests efficiently. Herein, the current study introduced a cationic star polymer (SPc) to prepare two types of nano-pesticides, which were co-applied with predatory stinkbugs Picromerus lewisi to achieve perfect cooperative pest control. The SPc exhibited nearly no toxicity against predatory stinkbugs at the working concentration, but it led to the death of predatory stinkbugs at extremely high concentration with the lethal concentration 50 (LC50) value of 13.57 mg/mL through oral feeding method. RNA-seq analysis revealed that the oral feeding of SPc could induce obvious stress responses, leading to stronger phagocytosis, exocytosis, and energy synthesis to ultimately result in the death of predatory stinkbugs. Then, the broflanilide and chlorobenzuron were employed to prepare the self-assembled nano-pesticides via hydrogen bond and Van der Waals force, and the complexation with SPc broke the self-aggregated structures of pesticides and reduced their particle sizes down to nanoscale. The bioactivities of prepared nano-pesticides were significantly improved toward common cutworm Spodoptera litura with the corrected mortality increase by approximately 30%. Importantly, predatory stinkbugs exhibited a strong predation selectivity for alive common cutworms to reduce the exposure risk of nano-pesticides, and the nano-pesticides showed negligible toxicity against predators. Thus, the nano-pesticides and predatory stinkbugs could be applied simultaneously for efficient and sustainable pest management. The current study provides an excellent precedent for perfect cooperative pest control via nano-pesticide and natural predator.
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Plaguicidas , Animales , Humanos , Plaguicidas/toxicidad , Ecosistema , Conducta Predatoria , Control Biológico de Vectores/métodos , Agricultura/métodos , Control de PlagasRESUMEN
Activation of stimulator of interferon genes (STING) by cyclic dinucleotides (CDNs) has been considered as a powerful immunotherapy strategy. While promising, the clinical translation of CDNs is still overwhelmed by its limited biostability and the resulting systemic immunotoxicity. Being differentiating from current application of exogenous CDNs to address these challenges, we herein developed one perylene STING agonist PDIC-NS, which not only promotes the production of endogenous CDNs but also inhibits its hydrolysis. More significantly, PDIC-NS can well reach lung-selective enrichment, and thus mitigates the systemic immunotoxicity upon intravenous administration. As a result, PDIC-NS had realized remarkable in vivo antitumor activity, and backward verified on STING knock out mice. Overall, this study states that PDIC-NS can function as three-in-one small-molecule STING agonist characterized by promoting the content and biostability of endogenous CDNs as well as possessing good tissue specificity, and hence presents an innovative strategy and platform for tumor chemo-immunotherapy.
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Neoplasias , Perileno , Animales , Ratones , Nucleótidos Cíclicos , Inmunoterapia/métodos , Proteínas de la Membrana/genética , Neoplasias/tratamiento farmacológicoRESUMEN
Drought stress is one of the most unfavorable factors affecting plant growth and productivity among various environmental stresses. Nanotechnology is expected to enhance the effectiveness of conventional biostimulants. Herein, the current study constructed an efficient proline (Pro) nanodelivery system based on a star polyamine (SPc). The hydroxyl groups of Pro could assemble with carbonyl groups of SPc, and the self-assembly of Pro with SPc formed the nanoscale particles of the Pro/SPc complex. Compared to Pro alone, the contact angle of SPc-loaded Pro decreased, and its retentivity and plant uptake increased. Importantly, the tobacco (Nicotiana benthamiana) seeds and seedlings treated with Pro/SPc complex exhibited stronger drought tolerance. RNA-Seq analysis indicated that the SPc-loaded Pro could further upregulate photosynthesis-related genes and endocytosis-related genes. The current study constructed an efficient nanodelivery system for improving the bioactivity of biostimulants, which has broad application prospects in the agricultural field.
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Resistencia a la Sequía , Compuestos Organoplatinos , Poliaminas , Espermina , Prolina/metabolismo , Adaptación Fisiológica/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genética , Sequías , Regulación de la Expresión Génica de las Plantas , Productos de TabacoRESUMEN
INTRODUCTION: Unscientific application of insecticides has led to severe resistance of pests to almost all classes of insecticides. Enhanced detoxification is the most common mechanism for this kind of resistance. OBJECT: Fall armyworm (FAW) has developed insecticide resistance, which is often linked to the overexpression of detoxification genes. Herein, a multicomponent nano-pesticide is designed to increase its broad-spectrum susceptibility toward insecticides. METHOD: Regulatory function of nuclear factor erythroid 2-related factor 2 (Nrf2) in detoxification was confirmed using transcriptome sequencing, quantitative real-time PCR and enzyme activity measurement. A star polycation (SPc) was adopted to construct the pesticide/SPc/complex, whose self-assembly mechanism and characterization were examined using isothermal titration calorimetry, dynamic light scattering and transmission electron microscope. The delivery efficiency of SPc-loaded dsRNA was examined in vitro and in vivo using fluorescent tracer technique. A multicomponent nano-pesticide was created through the integration of bacterial expression system and nano-delivery system, and its bioactivity was tested in laboratory and field. RESULTS: We confirmed the crucial role of Nrf2 in regulating the detoxification in FAW, and silencing Nrf2 could decrease detoxification gene expression and increase insecticide susceptibility. We then applied the SPc to self-assemble a nanoplatform for delivering Nrf2 double-stranded RNA (dsRNA) and pesticide simultaneously. Nano-sized pesticide/SPc/dsRNA complex exhibited high delivery efficiency in vitro and in vivo. Excitingly, the insecticidal activities of pesticide/SPc/dsNrf2 complexes were remarkably improved with the normalized synergistic ratios of 5.43-6.25 for chlorantraniliprole, 4.45-15.00 for emamectin benzoate, and 6.75-15.00 for spinetoram. Finally, we developed a multicomponent nano-pesticide (pesticide/SPc/dsNrf2 complex) using a bacterial expression system and nano-delivery system. This approach exhibited excellent leaf protection and pest control efficacy. CONCLUSION: The integration between the pesticide nanometerization and insecticide susceptibility improvement offers a promising strategy to increase insecticidal activity. Our study provides a revolutionary and universal strategy to increase insecticidal activity and decease application doses.
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A terrylenedicarboximide-anthraquinone dyad, FTQ, with absorption in the second near-infrared region (NIR-II) is obtained as a high-performance chromophore for photothermal therapy (PTT). The synthetic route proceeds by C-N coupling of amino-substituted terrylenedicarboximide (TMI) and 1,4-dichloroanthraquinone followed by alkaline-promoted dehydrocyclization. FTQ with extended π-conjugation exhibits an optical absorption band peaking at 1140 nm and extending into the 1500 nm range. Moreover, as determined by dielectric spectroscopy in dilute solutions, FTQ achieves an ultrastrong dipole moment of 14.4 ± 0.4 Debye due to intense intramolecular charge transfer. After encapsulation in a biodegradable polyethylene glycol (DSPE-mPEG2000), FTQ nanoparticles (NPs) deliver a high photothermal conversion efficiency of 49% under 1064 nm laser irradiation combined with excellent biocompatibility, photostability, and photoacoustic imaging capability. In vitro and in vivo studies reveal the great potential of FTQ NPs in photoacoustic-imaging-guided photothermal therapy for orthotopic liver cancer treatment in the NIR-II window.
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Nanopartículas , Técnicas Fotoacústicas , Terapia Fototérmica , Nanopartículas/química , Antracenos , Antraquinonas , Fototerapia , Técnicas Fotoacústicas/métodosRESUMEN
The application of nanotechnology in agriculture can break through many traditional problems of synthetic pesticides, especially for increasing bioactivity and reducing application amount. However, the safety and selective toxicity of nanocarrier-loaded pesticides should be clarified toward natural predators. In this context, an efficient spirotetramat nanodelivery system was successfully constructed based on a star polymer (SPc). Spirotetramat could complex with SPc through hydrogen bonding and van der Waals forces spontaneously. The self-assembly of the spirotetramat/SPc complex decreased the particle size of spirotetramat from 1292 to 710 nm. After the complexation with SPc, the lethal concentration 50 (LC50) values of spirotratemat decreased from 252.064 to 108.871 and 332.079 to 189.257 mg/L toward target pest Frankliniella occidentalis and nontarget predator Orius sauteri with the synergic ratios of 2.315 and 1.755, respectively. The possible reason might be due to the enhancement of the broad-spectrum toxicity of SPc-loaded pesticides. Importantly, the selective toxicity ratio (STR) of spirotetramat increased from 1.32 to 1.73 with the help of SPc, indicating the higher selectivity of the spirotratemat/SPc complex toward predators. Meanwhile, the safety coefficient (SC) of spirotratemat was not significantly changed after complexation with SPc, and the spirotratemat/SPc complex belonged to the medium risk pesticide. Overall, the assembly with SPc could not only improve the control efficacy of spirotetramat but also increase its selectivity as well as alleviate its negative effects on predators. The current study is beneficial for understanding the enhancement of broad-spectrum toxicity and the selective toxicity of nanocarrier-loaded pesticides.
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Perylene diimide (PDI)-based photothermal agents (PTAs) possess excellent stability and high photothermal conversion efficiency. However, developing PDIs with strong near-infrared absorption under biological conditions remains a challenge. In this study, we introduce a novel approach to facilitate the formation of J-aggregate-based PTAs with significantly red-shifted absorption by modulating steric hindrances of PDIs. PDIA, featuring larger steric hindrances at the bay position and smaller steric hindrances at the imide position, self-assembles into J-aggregates which exhibit a remarkable red-shift of over 100 nm. After encapsulation by DPSE-PEG, PDIA nanoparticles (PDIA-NPs) demonstrated a uniform and stable size, while retaining their significant red-shift. In vitro experiments demonstrated the great potential of PDIA-NPs in photothermal therapies for tumors and thrombi under 808 nm laser irradiation. This research provides valuable insights into the design of stable J-aggregates based on PDIs suitable for biological applications, paving the way for the development of more effective PTAs.
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Potato late blight caused by Phytophthora infestans is a devastating disease worldwide. Unlike other plant pathogens, double-stranded RNA (dsRNA) is poorly taken up by P. infestans, which is a key obstacle in using dsRNA for disease control. Here, a self-assembled multicomponent nano-bioprotectant for potato late blight management is designed based on dsRNA and a plant elicitor. Nanotechnology overcomes the dsRNA delivery bottleneck for P. infestans and extends the RNAi protective window. The protective effect of nano-enabled dsRNA against infection arises from a synergistic mechanism that bolsters the stability of dsRNA and optimizes its effective intracellular delivery. Additionally, the nano-enabled elicitor enhances endocytosis and amplifies the systemic defense response of the plants. Co-delivery of dsRNA and an elicitor provides a protective effect via the two aspects of pathogen inhibition and elevated plant defense mechanisms. The multicomponent nano-bioprotectant exhibits superior control efficacy compared to a commercial synthetic pesticide in field conditions. This work proposes an eco-friendly strategy to manage devastating plant diseases and pests.
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Phytophthora infestans , Solanum tuberosum , Solanum tuberosum/genética , Endocitosis , Inhibición Psicológica , Nanotecnología , ARN BicatenarioRESUMEN
Photothermal therapy (PTT) has emerged as a promising strategy for the treatment of tumors. However, the intrinsic self-repair mechanism of cells and the nonspecific photothermal effect of photothermal agents can result in poor treatment outcomes and normal tissue injury. To address this issue, we developed a dual light activatable perylenediimide derivative (P-NO) for nitric oxide-enhanced PTT. P-NO can self-assemble into nanoparticles in aqueous solutions. The P-NO nanoparticles are capable of releasing both NO and a photothermal molecule (P-NH) upon green light irradiation. The simultaneous release of NO and P-NH activates the photothermal effect and inhibits cell protection autophagy, thereby improving the therapeutic efficacy of PTT under near-infrared (NIR) light. Moreover, the switch on of NIR fluorescence allows real-time monitoring of the release of P-NH. Remarkably, in a mouse subcutaneous tumor model, significant tumor ablation can be achieved following dual light activated photothermal gas therapy. This work offers a promising and straightforward approach to constructing activatable perylenediimide-based photothermal agents for enhancing the effectiveness of photothermal gas therapy.
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Nanopartículas , Neoplasias , Animales , Ratones , Fototerapia , Neoplasias/patología , Autofagia , Línea Celular TumoralRESUMEN
RNA biopesticides are regarded as "the third revolution in the history of pesticides" due to their extensive advantages such as precision, high efficiency, green, pollution-free, etc. In the current study, two target genes encoding neuropeptide F receptor (NPFR) and AMP-activated protein kinase (AMPK), which are essential for insect feeding, cellular energy homeostasis and nutrient availability, were selected to design RNA pesticides. We achieved high RNA interference (RNAi) efficiency of npfr via a star polycation nanocarrier-based double-stranded RNA (dsRNA) delivery system. The food consumption of Ostrinia furnacalis is largely suppressed, which leads to a good protective effect on corn leaves. We determined the mechanism of the above genes. NPFR binds to the Gα protein and activates the intracellular second messengers cAMP and Ca2+, which in turn phosphorylate AMPK to regulate the synthesis and metabolism of lipids and glycogen. We then adopted a highly efficient bacteria-based expression system for the production of large amounts of dsRNA segments targeting npfr and ampk simultaneously and subsequently complexed them with nanocarriers to develop a novel dual-target RNA pesticide. Our RNA nanopesticide dramatically inhibits larval feeding, growth and development, and its controlling effect is even better than that of the widely used anti-feedant azadirachtin.
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Proteínas Quinasas Activadas por AMP , Zea mays , Animales , Zea mays/genética , Proteínas Quinasas Activadas por AMP/genética , Glucógeno , Interferencia de ARN , ARN Bicatenario , LípidosRESUMEN
Long-term overuse of chemical nematicides has resulted in low control efficacy toward destructive root-knot nematodes, and continuous development in nanotechnology is supposed to enhance the utilization efficiency of nematicides to meet practical needs. Herein, a cationic star polymer (SPc) was constructed to load fluopyram (flu) and prepare a flu nanoagent. Hydrogen bonding and van der Waals forces facilitated the self-assembly of the flu nanoagent, leading to the breakdown of self-aggregated flu and reducing its particle size to 60 nm. The bioactivity of flu was remarkably improved, with the half lethal concentration 50 from 8.63 to 5.70 mg/L due to the help of SPc. Transcriptome analysis found that a large number of transport-related genes were upregulated in flu nanoagent-exposed nematodes, while the expression of many energy-related genes was disturbed, suggesting that the enhanced uptake of flu nanoagents by nematodes might lead to the disturbance of energy synthesis and metabolism. Subsequent experiments confirmed that exposure to flu nanoagents markedly increased the reactive oxygen species (ROS) level of nematodes. Compared to flu treatment alone, succinate dehydrogenase (SDH) activity was inhibited in flu nanoagent-exposed nematodes with an increase in the pIC50 from 8.81 to 11.04, which further interfered with adenosine triphosphate (ATP) biosynthesis. Furthermore, the persistence of SPc-loaded flu in soil was prolonged by 2.33 times at 50 days after application. The protective effects of flu nanoagents on eggplant seedlings were significantly improved in both greenhouse and field trials, and the root-knot number was consistently smaller in roots treated with flu nanoagents than in those treated with flu alone. Overall, this study successfully constructed a self-assembled flu nanoagent with amplified effects on oxidative stress, SDH activity, and ATP generation, leading to highly effective control of root-knot nematodes in the field.
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Adenosina Trifosfato , Succinato Deshidrogenasa , Succinato Deshidrogenasa/metabolismo , Succinato Deshidrogenasa/farmacología , Adenosina Trifosfato/metabolismo , Antinematodos/farmacología , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
No effective fungicides are available for the management of Verticillium dahliae, which causes vascular wilt disease. In this study, a star polycation (SPc)-based nanodelivery system was used for the first time to develop a thiophanate-methyl (TM) nanoagent for the management of V. dahliae. SPc spontaneously assembled with TM through hydrogen bonding and Van der Waals forces to decrease the particle size of TM from 834 to 86 nm. Compared to TM alone, the SPc-loaded TM further reduced the colony diameter of V. dahliae to 1.12 and 0.64 cm, and the spore number to 1.13 × 108 and 0.72 × 108 cfu/mL at the concentrations of 3.77 and 4.71 mg/L, respectively. The TM nanoagents disturbed the expression of various crucial genes in V. dahliae, and contributed to preventing plant cell-wall degradation and carbon utilization by V. dahliae, which mainly impaired the infective interaction between pathogens and plants. TM nanoagents remarkably decreased the plant disease index and the fungal biomass in the root compared to TM alone, and its control efficacy was the best (61.20 %) among the various formulations tested in the field. Furthermore, SPc showed negligible acute toxicity toward cotton seeds. To the best of our knowledge, this study is the first to design a self-assembled nanofungicide that efficiently inhibits V. dahliae growth and protects cotton from the destructive Verticillium wilt.
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Ascomicetos , Tiofanato , Células Vegetales , Ascomicetos/metabolismo , Carbono/farmacología , Carbono/metabolismo , Gossypium/metabolismo , Enfermedades de las Plantas/microbiología , Resistencia a la Enfermedad/genética , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
Drug and gene delivery systems mediated by nanoparticles have been widely studied for life science in the past decade. The application of nano-delivery systems can dramatically improve the stability and delivery efficiency of carried ingredients, overcoming the defects of administration routes in cancer therapy, and possibly maintaining the sustainability of agricultural systems. However, delivery of a drug or gene alone sometimes cannot achieve a satisfactory effect. The nanoparticle-mediated co-delivery system can load multiple drugs and genes simultaneously, and improve the effectiveness of each component, thus amplifying efficacy and exhibiting synergistic effects in cancer therapy and pest management. The co-delivery system has been widely reported in the medical field, and studies on its application in the agricultural field have recently begun to emerge. In this progress report, we summarize recent progress in the preparation and application of drug and gene co-delivery systems and discuss the remaining challenges and future perspectives in the design and fabrication.
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Nanopartículas , Neoplasias , Humanos , Sistemas de Liberación de Medicamentos , Técnicas de Transferencia de Gen , Vehículos Farmacéuticos , Neoplasias/tratamiento farmacológicoRESUMEN
Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000-1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2-methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood-brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano-encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB-crossing due to the receptor-mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI-based NIR-II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM.
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Neoplasias Encefálicas , Glioblastoma , Nanopartículas , Perileno , Humanos , Glioblastoma/diagnóstico por imagen , Glioblastoma/terapia , Glioblastoma/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Barrera Hematoencefálica/patología , Fototerapia/métodos , Nanomedicina Teranóstica/métodosRESUMEN
Sepsis-induced uncontrolled systemic inflammatory response syndrome (SIRS) is a critical cause of multiple organ failure. Acute kidney injury (AKI) is one of the most serious complications associated with an extremely high mortality rate in SIRS, and it lacked simple, safe, and effective treatment strategies. Leontopodium leontopodioides (Willd.) Beauv (LLB) is commonly used in traditional Chinese medicine for the treatment of acute and chronic nephritis. However, it remains unclear whether lipopolysaccharide (LPS) affects LPS-induced AKI. To identify the molecular mechanisms of LLB in LPS-induced HK-2 cells and mice, LLB was prepared by extraction with 70% methanol, while a lipopolysaccharide (LPS)-induced HK-2 cell model and an AKI model were established in this study. Renal histopathology staining was performed to observe the morphology changes. The cell supernatant and kidney tissues were collected for determining the levels of inflammatory factors and protein expression by ELISA, immunofluorescence, and Western blot. The results indicated that LLB significantly reduced the expression of IL-6 and TNF-α in LPS-induced HK-2 cells, as well as the secretion of IL-6, TNF-α, and IL-1ß in the supernatant. The same results were observed in LPS-induced AKI serum. Further studies revealed that LLB remarkably improved oxidative stress and apoptosis based on the content of MDA, SOD, and CAT in serum and TUNEL staining results. Notably, LLB significantly reduced the mortality due to LPS infection. Renal histopathology staining results supported these results. Furthermore, immunofluorescence and Western blot results confirmed that LLB significantly reduced the expression of the protein related to the NF-κB signaling pathway and NLRP3, ASC, and Caspase-1 which were significantly increased through LPS stimulation. These findings clearly demonstrated the potential use of LLB in the treatment of AKI and the crucial role of the NF-κB/NLRP3 pathway in the process through which LLB attenuates AKI induced by LPS.
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Lesión Renal Aguda , FN-kappa B , Animales , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , Lipopolisacáridos/efectos adversos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Riñón , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/patologíaRESUMEN
Thoracic aortic dissection (TAD) is the most devastating complication of vascular disease. The accuracy of the clinical diagnosis and treatment of TAD at the early stage is still limited. Herein, we report a nano-delivery strategy for early diagnosis and the first case of interleukin-33 (IL-33) based therapy for the effective intervention of TAD. A targeted fluorescent nano vector (FNV) is designed to co-assemble with IL-33, which protects IL-33 and prolongs its half-life. With specific targeting ability to the thoracic aorta, FNV can diagnose TAD at its early stage through fluorescent imaging. FNV@IL-33 nanocomplex presents better therapeutic effects on mice TAD progression compared with that of IL-33 alone by reducing smooth muscle apoptosis. Administration of FNV@IL-33 two weeks before onset, the development of TAD is greatly intervened. Our study provides a novel approach for early diagnosis and effective IL-33 therapy of TAD, which opens attractive opportunities for clinical prevention of cardiovascular diseases.