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The therapeutic effects of many pharmacotherapies have been explored, but disadvantages such as low drug specificity, drug resistance and side effects makes their effective delivery to target sites a great challenge. Consequently, a distinctive prodrug-based technology have emerged as an effective treatments because of their distinctive advantages, such as high drug loading capacity, precise targeting, reduced side effects and spatial and temporal controllability. In particular, the use of gamma/X-ray-mediated strategies in radiotherapy is a new strategy that could enable the precise drug release from implanted devices. This review presents readers with the current state of prodrug therapy and reports the design protocols of rational and effective prodrugs for clinical use.
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The excessive emission of greenhouse gases, which leads to global warming and alarms the world, has triggered a global campaign for carbon neutrality. Carbon capture and sequestration (CCS) technology has aroused wide research interest as a versatile emission mitigation technology. Metal-organic frameworks (MOFs), as a new class of high-performance adsorbents, hold great potential for CO2 capture from large point sources and ambient air due to their ultra-high specific surface area as well as pore structure. In recent years, MOFs have made great progress in the field of CO2 capture and separation, and have published a number of important results, which have greatly promoted the development of MOF materials for practical carbon capture applications. This review summarizes the most recent advanced research on MOF materials for carbon capture in various application scenarios over the past six years. The strategies for enhancing CO2 selective adsorption and separation of MOFs are described in detail, along with the development of MOF-based composites. Moreover, this review also systematically summarizes the highly concerned issues of MOF materials in practical applications of carbon capture. Finally, future research on CO2 capture by MOF materials is prospected.
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Poly (ß-amino ester) (PBAE) is a class of biodegradable polymers containing ester bonds in their main chain, extensively investigated as cationic polymer carriers for siRNA. Most current PBAE carriers rely on termination with hydrophilic or charged amines. In this study, a polymer platform consisting of 168 PBAE polymers with hydrophobic alkyl chain terminals is constructed through sequential aza-Michael addition. A large number of effective carriers are identified through in vitro screening of the PBAE platform for siLuc delivery to HeLa-Luc cells. Specifically, PA8-C6 and PA8-C8 achieve remarkable gene knockdown efficacies of up to 80% with low cytotoxicity. Certain materials from the PA2 and PA5 series demonstrate potent siRNA delivery capabilities associated with elevated cytotoxicity. The pKa value of PBAE is predominantly determined by the hydrophilic amine side chains rather than the end-capping groups. A pKa range of ≈6.2-6.5 may contribute to the excellent delivery capability for PA8 series carriers. The co-formulation of PBAE carriers with helper lipids leads to the reduced size and surface charges of the polyplex NPs with siRNA, consequently decreasing the cytotoxicity and enhancing siRNA delivery efficacy. These findings hold significant implications for the development of novel degradable polymer carriers for siRNA delivery.
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PURPOSE: The purpose of this study was to explore the expression, prognostic value and immune correlation of Cofilin 1 protein(CFL-1) in head and neck squamous cell carcinoma(HNSCC). METHODS: The expression and prognostic value of CFL-1 in head and neck squamous cell carcinoma(HNSCC) was explored in the cancer genome map database (TCGA) and gene expression total databases (GEO), and the potential immune pathway of CFL-1 in HNSCC was revealed by GESA and cibersoft analysis. The data were statistically analyzed using SPSS 26.0 software package. RESULTS: CFL-1 was significantly up-regulated in HNSCC tissue. The expression level of CFL-1 was significantly correlated with the overall survival status of HNSCC. High expression of CFL-1 was significantly associated with a lower overall survival rate. In addition, multivariate Cox survival analysis showed that CFL-1 expression was independent predictors of poor prognosis of HNSCC. GESA and cibersoft analysis showed that the imbalance of CFL-1 expression affected multiple signal pathways and infiltration of immune cells. CONCLUSIONS: CFL-1 is highly expressed in HNSCC and is significantly associated with poor prognosis of NHSCC. It is a potential prognostic marker of HNSCC.
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Cofilina 1 , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Cofilina 1/genética , Cofilina 1/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/metabolismo , Taxa de Sobrevida , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Modelos de Riscos ProporcionaisRESUMO
The dense extracellular matrix and high interstitial pressure affect the diffusion of nanodrug in tumor tissue, resulting in a small range of action of the active components in nanodrug, thereby affecting its anticancer efficacy. In order to enhance the diffusion ability of nanodrug, a dual-bubble/photothermal-driven nanomissile (HA@MnO2@TA/Fe/ICG/TPZ, HMTAFIT) was designed through "four in one" anti-tumor strategy. Harnessing the capabilities of hyaluronic acid, a biomacromolecule, the nanomotor transforms into a nanomissile, targeting cancer cells with precision. The oxygen generated by the reaction of manganese dioxide with hydrogen peroxide and the local temperature rise of indocyanine green under near-infrared light endow HMTAFIT with the ability of bubble/photothermal dual-driven, and the outermost layer of modified hyaluronic acid incubates the targeting properties of HMTAFIT which could avoid damage to normal cells. The bubble/photothermal-dual-driven increases motion speed of HMTAFIT by 13.8 µm/s, and the enhanced "four in one" anti-tumor strategy effectively improved the anticancer efficacy. The precision-guided nanomissile boasts the capability to eliminate deep-seated cancer cells and overcome multidrug resistance via optimized diffusion and a cutting-edge "four-in-one" approach.
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Flexible polyurethane foam (FPUF) is a ubiquitous material utilized in furniture cushions, mattresses, and various technical applications. Despite the widespread use, FPUF faces challenges in maintaining long-lasting flame retardancy and aging resistance, particularly in harsh environments, while retaining mechanical robustness. Here, we present a novel approach to address these issues by enhancing FPUF through multiple free-radical-trapping and hydrogen-bonding mechanisms. A hindered amine phosphorus-containing polyol (DTAP) was designed and chemically introduced into FPUF. The distinctive synergy between hindered amine and phosphorus-containing structures enables the formation of multiple hydrogen bonds with urethane, while also effectively capturing free radicals across a broad temperature spectrum. As a result, incorporating only 5.1 wt% of DTAP led to the material successfully passing vertical burning tests and witnessing notable enhancements in tensile strength, elongation at break, and tear strength. Even after enduring accelerated thermal aging for 168 hours, the foam maintained exceptional flame retardancy and mechanical properties. This study offers novel insights into material enhancement, simultaneously achieving outstanding long-lasting flame retardancy, toughness, and anti-aging performance.
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Polyurethane (PU) foams, pivotal in modern life, face challenges suh as fire hazards and environmental waste burdens. The current reliance of PU on potentially ecotoxic halogen-/phosphorus-based flame retardants impedes large-scale material recycling. Here, our demonstrated controllable catalytic cracking strategy, using cesium salts, enables self-evolving recycling of flame-retardant PU. The incorporation of cesium citrates facilitates efficient urethane bond cleavage at low temperatures (160 °C), promoting effective recycling, while encouraging pyrolytic rearrangement of isocyanates into char at high temperatures (300 °C) for enhanced PU fire safety. Even in the absence of halogen/phosphorus components, this foam exhibits a substantial increase in ignition time (+258.8%) and a significant reduction in total smoke release (-79%). This flame-retardant foam can be easily recycled into high-quality polyol under mild conditions, 60 °C lower than that for the pure foam. Notably, the trace amounts of cesium gathered in recycled polyols stimulate the regenerated PU to undergo self-evolution, improving both flame-retardancy and mechanical properties. Our controllable catalytic cracking strategy paves the way for the self-evolutionary recycling of high-performance firefighting materials.
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Polymer-based nanomotors are attracting increasing interest in the biomedical field due to their microscopic size and kinematic properties which support overcoming biological barriers, completing cellular uptake and targeted blasting in limited spaces. However, their applications are limited by the complex viscous physiological environment and lack of sufficient biocompatibility. This manuscript firstly reports a natural melanin nano-missile of MNP@HA-EDA@Urease@AIE PS (MHUA) based on photothermally accelerated urease-driven to achieve chemodrug-free phototherapy. Compared to conventional nano-missiles that only provide driving force, this photothermally accelerated urease-driven nanomotor is independent of chemodrug to maximise biocompatibility, and achieve ideal therapeutic effect through targeted PTT/PDT. In particular, the thermal effect can not only boost the catalytic activity of urease but also achieve ideally anti-tumor effect. In addition, guided by and AIE PS, the nanomotor can generate 1O2 to achieve PDT and be traced in real time serving as an effective fluorescent bio-radar for intracellular self-reporting during cancer treatment. Finally, the targeting ability of MUHA is provided by hyaluronan. Taken together, this MHUA platform provides a simple and effective strategy for target/fluorescence radar detective-guided PTT/PDT combination, and achieves good therapeutic results without chemodrug under thermal accelerated strategy, providing a new idea for the construction of chemodrug-free nanomotor-therapy system.
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Ácido Hialurônico , Melaninas , Urease , Humanos , Linhagem Celular Tumoral , Decapodiformes , Ácido Hialurônico/química , Melaninas/química , Nanopartículas/química , Fototerapia/métodos , Urease/química , Urease/metabolismo , AnimaisRESUMO
Ningxin-Tongyu-Zishen formula (NTZF) is a clinical experience formula for the treatment of premature ovarian insufficiency (POI) in traditional Chinese medicine (TCM), and the potential mechanism is unknown. For in vivo experiments, POI mouse models (C57BL/6 mice), were constructed by subcutaneous injection of D-galactose (D-gal, 200 mg/kg). After treatment of NTZF (10.14, 20.27, 40.54 g/kg;) or estradiol valerate (0.15 mg/kg), ovarian function, oxidative stress (OS) and protein expression of Sirt1/p53 were evaluated. For in vitro experiments, H2O2 (200 µM) was used to treat KGN to construct ovarian granulosa cells (OGCs) cell senescence model. Pretreatment with NTZF (1.06 mg/mL) or p53 inhibitor (Pifithrin-α, 1 µM) was performed before induction of senescence, and further evaluated the cell senescence, OS, mRNA and protein expression of Sirt1/p53. In vivo, NTZF improved ovarian function, alleviated OS and Sirt1/p53 signaling abnormalities in POI mice. In vitro experiments showed that NTZF reduced the level of OS and alleviated the senescence of H2O2-induced KGN. In addition, NTZF activated the protein expression of Sirt1, inhibited the mRNA transcription and protein expression of p53 and p21. Alleviating OGCs senescence and protecting ovarian function through Sirt1/p53 is one of the potential mechanisms of NTZF in the treatment of POI.
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Galactose , Insuficiência Ovariana Primária , Humanos , Feminino , Camundongos , Animais , Galactose/toxicidade , Sirtuína 1/genética , Sirtuína 1/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Camundongos Endogâmicos C57BL , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/genética , Células da Granulosa/metabolismo , Senescência Celular , RNA Mensageiro/metabolismoRESUMO
The problem of antibiotic resistance seriously affects the treatment of bacterial infections, so there is an urgent need to develop novel antibiotic-independent antimicrobial strategies. Herein, a urease-driven bowl-like mesoporous polydopamine nanorobot (MPDA@ICG@Ur@Man) based on single-wavelength near-infrared (NIR) remote photothermal acceleration to achieve antibiotic-free phototherapy(photothermal therapy, PTT, plus photodynamic therapy, PDT) is first reported. The smart nanorobots can perform active movement by decomposing urea to produce carbon dioxide and ammonia. Particularly, the elevated local temperature during PTT can increase urease activity to enhance the autonomous movement and thus increase the contact between the antimicrobial substance and bacteria. Compared with a nanomotor propelled by urea only, the diffusion coefficient (De) of photothermal-accelerated nanorobots is increased from 1.10 to 1.26 µm2 s-1. More importantly, urease-driven bowl-like nanorobots with photothermal enhancement can specifically identify Escherichia coli (E. coli) and achieve simultaneous PTT/PDT at a single wavelength with 99% antibactericidal activity in vitro. In a word, the urease-driven bowl-like nanorobots guided by photothermal-accelerated strategy could provide a novel perspective for increasing PTT/PDT antibacterial therapeutic efficacy and be promising for various antibiotic-free sterilization applications.
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Escherichia coli , Indóis , Polímeros , Urease , Urease/metabolismo , Urease/química , Indóis/química , Indóis/farmacologia , Polímeros/química , Escherichia coli/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos , HumanosRESUMO
The development of safe and effective delivery systems is critical for the clinical applications of siRNA-based therapeutics. Polymer-based vectors have garnered significant attention owing to their structural flexibility and functional tunability. Polyethyleneimine (PEI) has been extensively studied for nucleic acid delivery; nevertheless, its high cytotoxicity has posed challenges for clinical applications. In this study, we have reported poly(glycidyl amine) (PGAm), a linear PEI analogue, demonstrating remarkable siRNA delivery efficacy and improved biocompatibility. By introducing three aromatic moieties (tyrosine, p-hydroxybenzenepropanoic acid, and phenylalanine) at varying ratios to further modify PGAms, we successfully constructed a library comprising 36 PGAm-based carriers. In vitro evaluations revealed that PGAm-based carriers exhibited significantly enhanced biocompatibility and reduced non-specific protein absorption in comparison to PEI25k. Among them, 10 modified PGAms achieved a knockdown of target gene expressions exceeding 80%, and 26 modified PGAms maintained over 70% cell viability when utilized for the in vitro delivery of siRNA to HeLa cells. Explorations into the structure-activity relationship of PGAm-based polyplex nanoparticles (NPs) indicated that the siRNA delivery efficacy of NPs depended on factors such as the molecular weight of PGAm precursors, the type of modifying moieties, and the modification ratio. Furthermore, it was demonstrated that two top-performing NPs, namely 2T100/siLuc and 2A50/siLuc, exhibited potent silencing of target genes in tumors following i.v. injection into mice bearing HeLa-Luc xenografts. The in vivo efficacy of the selected NPs was further validated by a remarkable anti-cancer effect when employed for the delivery of siRNA targeting polo-like kinase 1 (siPLK1) to mice with PC-3 xenograft tumors. The intravenous administration of NPs resulted in a substantial inhibition of tumor growth without significant toxicity. These findings demonstrate the feasibility of employing PGAm in siRNA delivery and provide valuable insights for the development of efficient siRNA carriers based on PGAm.
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Aminas , Neoplasias , Humanos , Animais , Camundongos , Células HeLa , RNA Interferente Pequeno/metabolismo , Linhagem Celular Tumoral , PolímerosRESUMO
This study utilized transmission electron microscopy (TEM) and on-axis transmission Kikuchi diffraction (TKD) to investigate the fatigue-induced HCP-to-FCC phase transformation in industrial pure zirconium under a stress ratio of R = 0.1. The results show that fatigue damages result from phase deformations during cyclic loadings. The fatigue-induced FCC-Zr phases exhibit a B-type orientation relationship with the HCP-Zr matrix. Notedly, due to the different growth directions of Shockley partial dislocations relative to nucleation points, there are two FCC-Zr variants after the HCP-to-FCC phase transformation. The content of these two variants accounts for 65% and 35% of the total FCC-Zr, respectively, appearing as lamellae morphology embedded parallelly within the matrix. The distribution of the two variants includes isolated distribution and adjacent distribution. For the adjacent distribution, a twinning relationship is observed between the two variants. Meanwhile, as an intermediate transition stage of the HCP-to-FCC phase transformation, stacking faults are observed at the boundaries of the FCC-Zr lamellae. These findings offer insights into the microstructural features and formation mechanisms of fatigue-induced HCP-to-FCC phase transformation.
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Efficient and safe delivery of vulnerable mRNA is a long-standing challenge for the broad application of the emerging mRNA-based therapeutics. Herein, a combinatorial library containing 119 novel lipids was constructed via sequential aza-Michael addition reactions of arylates and varying amines to tackle the ongoing challenge in mRNA delivery. Through in vitro screening of the lipid library on IGROV 1 cells, we identified several synthetic lipids with superior mRNA delivery efficacy. The delivery capability of these lipids was verified by the potent expression of luciferase in BALB/c mice upon intravenous administration of luciferase-encoding mRNA lipid nanoparticles (LNPs). Further investigations on the structure-activity relationship revealed that lipids with branched hydrophobic tails were better at delivering mRNA than those containing linear tails at the similar total number of carbons. In comparison to linear tails, the branched tails endowed LNPs with less inner hydrophobicity, fewer surface charges, and proper stability, which benefits the cellular uptake of LNPs and the intracellular trafficking of mRNA, thus improves the delivery efficacy of mRNA. The therapeutical potential of the lead LNPs was evaluated by delivering ovalbumin (OVA)-encoding mRNA to mice bearing B16-OVA melanoma tumors. The results demonstrated that the administration of OVA mRNA LNPs significantly activated CD8+ T cells in tumor microenvironment and substantially prohibited the growth of the aggressive B16-OVA tumors. The robust antitumor efficacy highlights the great potential of these LNPs in cancer immunotherapy.
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Linfócitos T CD8-Positivos , Melanoma Experimental , Animais , Camundongos , Imunoterapia , Lipossomos , Ovalbumina , Melanoma Experimental/terapia , Lipídeos , Microambiente TumoralRESUMO
Some Zinc finger (ZnF) proteins are required for masculinization in silkworms. In the present study, a masculinizer gene (Mr-Masc) with multi-tissue expression is identified in the freshwater prawn Macrobrachium rosenbergii. The Mr-Masc is clustered into a separate branch with ZnF proteins from decapoda by phylogenetic tree analysis. Moreover, Mr-Masc silencing in male postlarvae prawn results in functional sex reversal females known as neo-females, which are applied to all-male monosex offspring breeding. This manipulation has been significant in sexually dimorphic cultured species. In addition, several significantly expressed transcripts are enriched and the effects of crucial signal pathways are focused through the comparative transcriptomic analysis in Mr-Masc gene knockdown. The significantly differentially expressed epidermal growth factor, upregulated low-density lipoprotein receptor, flotillin, and sex-lethal unigenes, downregulated heat shock proteins and forkhead box homologs are focused. The finding offers an innovative perspective on Masc proteins' evolution and physiological function.
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Glyphodes pyloalis Walker (G. pyloalis) is a common destructive mulberry pest. Due to the long-term and frequent use of insecticides, it has developed tolerance to commonly used insecticides. Tolfenpyrad (TFP) is a novel pyrazole heterocyclic insecticide. In order to understand the TFP detoxification mechanism of G. pyloalis larvae, we first estimated the LC30 dose of TFP for 3rd instar G. pyloalis larvae. Next, we identified genes that were differentially expressed in 3rd instar G. pyloalis larvae treated with TFP compared to the control group by transcriptome sequencing. In total, 86,949,569 and 67,442,028 clean reads were obtained from TFP-treated and control G. pyloalis larvae, respectively. A total of 5588 differentially expressed genes (DEGs) were identified in TFP-treated and control G. pyloalis larvae, of which 3084 genes were upregulated and 2504 genes were downregulated. We analyzed the expression of 43 candidate detoxification enzyme genes associated with insecticide tolerance using qPCR. According to the spatiotemporal expression pattern of DEGs, we found that CYP6ABE1, CYP333A36 and GST-epsilon8 were highly expressed in the midgut, while CarEs14 was strongly expressed in haemolymph. Furthermore, we successfully knocked down these genes by RNA interference. After silencing CYP6ABE1 and CYP333A36, bioassay showed that the mortality rate of TFP-treated G. pyloalis larvae was significantly higher compared to the control group. This study provides a theoretical foundation for understanding the sensitivity of G. pyloalis to TFP and establish the basis for the effective and green management of this pest.
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Inseticidas , Mariposas , Animais , Inseticidas/farmacologia , Inseticidas/metabolismo , Mariposas/metabolismo , Larva/genética , Pirazóis/metabolismoRESUMO
Foodborne illness caused by Staphylococcus aureus (S. aureus) has posed a significant threat to human health. Herein, an integrated multifunctional nanoplatform was developed for fluorescence detection and inactivation of S. aureus based on cascade signal amplification coupled with single strand DNA-template copper nanoparticles (ssDNA-Cu NPs). Benefiting from reasonable design, one-step cascade signal amplification was achieved through strand displacement amplification combined with rolling circle amplification, followed by in-situ generation of copper nanoparticles. S. aureus detection could be performed through naked eye observation and microplate reader measurement of the red fluorescence signal. The multifunctional nanoplatform had satisfactory specificity and sensitivity, achieving 5.2 CFU mL-1 detection limit and successful detection of 7.3 CFU of S. aureus in spiked egg after < 5 h of enrichment. Moreover, ssDNA-Cu NPs could eliminate S. aureus to avoid secondary bacterial contamination without further treatment. Therefore, this multifunctional nanoplatform has potential application in food safety dtection.
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Técnicas Biossensoriais , Staphylococcus aureus , Humanos , Staphylococcus aureus/genética , Cobre , Técnicas de Amplificação de Ácido Nucleico , DNA de Cadeia Simples , Limite de DetecçãoRESUMO
Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.
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Antineoplásicos , Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Fármacos por Nanopartículas , Antineoplásicos/química , Ácidos Borônicos , Neoplasias/tratamento farmacológico , Concentração de Íons de Hidrogênio , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Linhagem Celular Tumoral , Paclitaxel/química , Portadores de Fármacos/química , Microambiente TumoralRESUMO
Nanomotors, as a new type of micro-device, show good performance in terms of rapid transportation and deep penetration through their autonomous motion. However, their ability to efficiently break physiological barriers still remains a great challenge. Herein, we first developed a thermal-accelerated urease driven human serum albumin (HSA) nanomotor based on photothermal intervention (PTI) to achieve chemotherapy drugfree-phototherapy. The HANM@FI (HSA-AuNR@FA@Ur@ICG) is composed of a main body of biocompatible HSA, modified by gold nanorods (AuNR) and loaded with functional molecules of folic acid (FA) and indocyanine green (ICG). It promotes its own motion by breaking down urea to produce carbon dioxide and ammonia. In particular, the nanomotor is conveniently operated via near-infrared combined photothermal therapy (PTT)/ photodynamic therapy (PDT) to achieve an accelerated De value from 0.73 µm2s-1 to 1.01µm2s-1, and ideal tumor ablation at the same time. In contrast to customary urease-driven nanodrug-stacked engine, this HANM@FI has both targeting and imaging-guided capabilities, and finally achieves superior anti-tumor effects without chemotherapy drugs, through a "two-in-one" (motor mobility plus unique phototherapy in chemotherapy-drugfree phototherapy) strategy. This PTI effect with urease-driven nanomotors may offer further possibilities for future clinical applications of nanomedicines by enabling deep penetration and a subsequent chemotherapy-drugfree combination therapy strategy.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Urease , Albumina Sérica Humana , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Verde de Indocianina/farmacologia , Linhagem Celular TumoralRESUMO
RNA interference (RNAi) is a promising approach for disease treatments. But the development of safe and effective delivery carriers remains a major challenge. Organic-inorganic hybrid nanoparticles (NPs), with the integration of functions from distinct materials, show great potential in small interfering RNA (siRNA) delivery. Herein, pH responsive amorphous calcium carbonate NPs (ACC NPs) are prepared using flash nanoprecipitation and hybrid NPs are constructed by coating ACC NPs with polyethyleneimine (PEI) for efficient siRNA delivery. PEI/ACC NPs show robust pH responsiveness and stability as well as effective siRNA loading and protection. Furthermore, siRNA-loaded PEI/ACC NPs demonstrate enhanced cellular uptake and efficient endosomal escape, mediating improved siRNA delivery compared to pure PEI. These findings suggest that PEI/ACC NPs may have great potential in siRNA delivery for RNAi-based therapy.
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Nanopartículas , Polietilenoimina , RNA Interferente Pequeno/genética , Interferência de RNA , Carbonato de CálcioRESUMO
N6-methyladenosine (m6A) plays a key role in many biological processes. However, the function and evolutionary relationship of m6A-related genes in insects remain largely unknown. Here we analysed the phylogeny of m6A-related genes among 207 insect species and found that m6A-related genes are evolutionarily conserved in insects. Subcellular localization experiments of m6A-related proteins in BmN cells confirmed that BmYTHDF3 was localized in the cytoplasm, BmMETTL3, BmMETTL14, and BmYTHDC were localized in the nucleus, and FL2D was localized to both the nucleus and cytoplasm. We examined the expression patterns of m6A-related genes during the embryonic development of Bombyx mori. To elucidate the function of BmMETTL3 during the embryonic stage, RNA sequencing was performed to measure changes in gene expression in silkworm eggs after BmMETTL3 knockdown, as well as in BmN cells overexpressing BmMETTL3. The global transcriptional pattern showed that knockdown of BmMETTL3 affected multiple cellular processes, including oxidoreductase activity, transcription regulator activity, and the cation binding. In addition, transcriptomic data revealed that many observed DEGs were associated with fundamental metabolic processes, including carbon metabolism, purine metabolism, amino acid biosynthesis, and the citrate cycle. Interestingly, we found that knockdown of BmMETTL3 significantly affected Wnt and Toll/Imd pathways in embryos. Taken together, these results suggest that BmMETTL3 plays an essential role in the embryonic development of B. mori, and deepen our understanding of the function of m6A-related genes in insects.