RESUMEN
The stimuli-responsive nano-carriers are at the forefront of research in nanotechnology and materials science. These advanced systems are designed to alter their physicochemical properties upon exposure to specific stimuli, enabling controllable and targeted delivery of therapeutic agents. Nevertheless, limited endosomal escape reduces the drug bioavailability in clinical use. We herein report azobenzene (Azo)-based liposomes, prepared by co-assembling the photoisomerizable cationic Azo lipids and helper lipids, which achieve controllable doxorubicin (Dox) release and enhanced cytosolic transport upon light irradiation. Azo lipids undergo reversible isomerization between cis-isomers and trans-isomer when received UV and visible (Vis) light irradiation, causing liposomal membrane permeability changes for controlled drug release. Moreover, the nanomechanical action created by the isomerization of Azo lipids promotes the endosomal escape of the liposomes. DSPC-Azo liposomes, with minimal Dox leakage, showed significant tumor cell killing upon irradiation. For in vivo study, we co-encapsulated the upconverting nanoparticles (UCNPs), which can convert the near-infrared (NIR) light into UV/Vis emissions, facilitating Azo units activation. UCNP/Dox-loaded DSPC-Azo liposomes inhibited tumor growth under NIR irradiation in a 4T1 tumor-bearing mouse model.
RESUMEN
BACKGROUND: The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4). RESULTS: There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis. CONCLUSION: Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.
Asunto(s)
Biomarcadores , Glucemia , Enfermedad del Hígado Graso no Alcohólico , Encuestas Nutricionales , Triglicéridos , Humanos , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/mortalidad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Triglicéridos/sangre , Medición de Riesgo , Glucemia/metabolismo , Biomarcadores/sangre , Adulto , Pronóstico , Factores de Riesgo , Factores de Tiempo , Anciano , Estados Unidos/epidemiología , Causas de Muerte , Valor Predictivo de las Pruebas , Índice de Masa Corporal , Hígado Graso/mortalidad , Hígado Graso/sangre , Hígado Graso/diagnóstico , Circunferencia de la CinturaRESUMEN
Tumor cells harness Ca2+ to maintain cellular homeostasis and withstand external stresses from various treatments. Here, a dual-channel Ca2+ nanomodulator (CAP-P-NO) is constructed that can induce irreversible intracellular Ca2+ disorders via the redistribution of tumor-inherent Ca2+ for disrupting cellular homeostasis and thus improving tumor radiosensitivity. Stimulated by tumor-overexpressed acid and glutathione, capsaicin and nitric oxide are successively escaped from CAP-P-NO to activate the transient receptor potential cation channel subfamily V member 1 and the ryanodine receptor for the influx of extracellular Ca2+ and the release of Ca2+ in the endoplasmic reticulum, respectively. The overwhelming level of Ca2+ in tumor cells not only impairs the function of organelles but also induces widespread changes in the gene transcriptome, including the downregulation of a set of radioresistance-associated genes. Combining CAP-P-NO treatment with radiotherapy achieves a significant suppression against both pancreatic and patient-derived hepatic tumors with negligible side effects. Together, the study provides a feasible approach for inducing tumor-specific intracellular Ca2+ overload via endogenous Ca2+ redistribution and demonstrates the great potential of Ca2+ disorder therapy in enhancing the sensitivity for tumor radiotherapy.
Asunto(s)
Calcio , Humanos , Calcio/metabolismo , Animales , Línea Celular Tumoral , Ratones , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/química , Tolerancia a Radiación/efectos de los fármacos , Neoplasias/metabolismo , Neoplasias/radioterapia , Neoplasias/tratamiento farmacológicoRESUMEN
Autophagy is an important biological mechanism for eukaryotic cells to regulate growth, death, and energy metabolism, and plays an important role in removing damaged organelles, misfolded or aggregated proteins, and clearing pathogens. It has been found that autophagy is closely related to cell survival and death, and is of great significance in cancerigenesis and development, playing a bidirectional role in cancer inhibition and cancer promotion. Therefore, treating cancers by regulating autophagy has attracted much attention. A large amount of research evidence indicates that polymeric nanomaterials are able to regulate cellular autophagy, and their good biocompatibility, degradability, and functionalizable modification open up a broad application prospect for improving the therapeutic effect of cancers. This review provides an overview of the research progress of polymeric nanomaterials for modulating autophagy in the treatment of cancers.
RESUMEN
Fusobacterium nucleatum (Fn) is an oral anaerobic bacterium that has recently been found to colonize on the surface of colorectal cancer cells in humans, and its degree of enrichment is highly negatively correlated with the prognosis of tumor treatment. Numerous studies have shown that Fn is involved in the occurrence and development of colorectal cancer (CRC), and Fn interacts with multiple components in the tumor microenvironment to increase tumor resistance. In recent years, researchers have begun using nanomedicine to inhibit Fn's proliferation at the tumor site or directly target Fn to treat CRC. This review summarizes the mechanism of Fn in promoting CRC and the latest research progress on Fn-related CRC therapy using different nanomaterials. Finally, the applications perspective of nanomaterials in Fn-promoted CRC therapy was prospected.
Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/terapia , Neoplasias Colorrectales/patología , Fusobacterium nucleatum/genética , Composición de Base , ARN Ribosómico 16S , Filogenia , Análisis de Secuencia de ADN , Microambiente TumoralRESUMEN
BACKGROUND: N6-methyladenosine (m6A), the most prevalent internal RNA modification in eukaryotic cells, is dynamically regulated in response to a wide range of physiological and pathological states. Nonetheless, the involvement of METTL14-induced m6A in liver fibrosis (LF) has yet to be established. METHODS: In vitro, HSC cell lines with knock-down and overexpression of METTL14 were constructed, and the effects of METTL14 gene on the phenotypic function of activated HSCs were observed. The proliferation rate was measured by CCK8 and EDU, the cell proliferation cycle was measured by flow detector, the migration rate was measured by Transwell, and the contractility of F-actin was observed after phalloidin staining. The downstream target gene NOVA2 of METTL14 was screened by combined sequencing of MeRIP-seq and RNA-seq, combined with signal analysis. Adeno-associated virus (AAV) was injected into the tail vein in vivo to knock down the expression of METTL14, so as to further observe the role of METTL14 in the progress of LF. RESULTS: our research showed that the methylase METTL14 content was decreased in hepatic tissue from patients with LF, leading to a lowered degree of m6A modification. Functionally, we discovered that knocking down m6A methyltransferase METTL14 led to increased HSC activation and a substantial worsening of LF. Mechanically, as shown in a multiomics study of HSCs, depleting METTL14 levels decreased m6A deposition onNOVA2 mRNA transcripts, which prompted the activation of YTHDF2 to detect and degrade the decrease of NOVA2 mRNA. CONCLUSIONS: METTL14 functioned as a profibrotic gene by suppressing NOVA2 activity in a mechanism dependent on m6A-YTHDF2. Moreover, knocking down METTL14 exacerbated LF, while NOVA2 prevented its development and partly reversed the damage.
Asunto(s)
Cirrosis Hepática , Factores de Transcripción , Humanos , Cirrosis Hepática/genética , Actinas , Metiltransferasas/genética , Antígeno Ventral Neuro-Oncológico , Proteínas de Unión al ARN/genéticaRESUMEN
Cancer stem-like cells (CSCs), capable of indefinite self-renewal and differentiation, are considered to be the root cause of tumor radiotherapy (RT) resistance. However, the CSCs-targeted therapy still remains to be a great challenge because they are commonly located in the deep tumor making drugs hard to approach, and their hypoxic and acidic niche can further aggravate radioresistance. Herein, based on the finding that hypoxic CSCs highly express carbonic anhydrase IX (CAIX) on the cell membrane, a CAIX-targeted induced in situ self-assembly system on the surface of CSC is reported to overcome hypoxic CSC-mediated radioresistance. Via the sequential processes of "monomer release-target accumulation-surface self-assembly", the constructed peptide-based drug delivery system (CA-Pt) exhibits the advantages of deep penetration, amplified CAIX inhibition, and enhanced cellular uptake, which greatly relieves the hypoxic and acidic microenvironment to promote the hypoxic CSC differentiation and combines with platinum to boost the RT-inducing DNA damage. In both lung cancer tumor mouse and zebrafish embryo models, CA-Pt treatment can effectively assist RT in suppressing tumor growth and preventing tumor invasion and metastasis. This study uses a surface-induced self-assembly strategy to differentiate hypoxic CSCs, which may provide a universal treatment strategy for overcoming tumor radioresistance.
Asunto(s)
Neoplasias Pulmonares , Pez Cebra , Animales , Ratones , Línea Celular Tumoral , Péptidos , Diferenciación Celular , Microambiente TumoralRESUMEN
BACKGROUND: Cryptotanshinone (CPT) has wide biological functions, including anti-oxidative, antifibrosis, and anti-inflammatory properties. However, the effect of CPT on hepatic fibrosis is unknown. AIM: To investigate the effects of CPT treatment on hepatic fibrosis and its underlying mechanism of action. METHODS: Hepatic stellate cells (HSCs) and normal hepatocytes were treated with different concentrations of CPT and salubrinal. The CCK-8 assay was used to determine cell viability. Flow cytometry was used to measure apoptosis and cell cycle arrest. Reverse transcription polymerase chain reaction (RT-PCR) and Western blot analyses were used to measure mRNA levels and protein expression of endoplasmic reticulum stress (ERS) signaling pathway related molecules, respectively. Carbon tetrachloride (CCL4) was used to induce in vivo hepatic fibrosis in mice. Mice were treated with CPT and salubrinal, and blood and liver samples were collected for histopathological examination. RESULTS: We found that CPT treatment significantly reduced fibrogenesis by modulating the synthesis and degradation of the extracellular matrix in vitro. CPT inhibited cell proliferation and induced cell cycle arrest at the G2/M phase in cultured HSCs. Furthermore, we found that CPT promoted apoptosis of activated HSCs by upregulating expression of ERS markers (CHOP and GRP78) and activating ERS pathway molecules (PERK, IRE1α, and ATF4), which were inhibited by salubrinal. Inhibition of ERS by salubrinal partially eliminated the therapeutic effect of CPT in our CCL4-induced hepatic fibrosis mouse model. CONCLUSION: CPT can promote apoptosis of HSCs and alleviate hepatic fibrosis through modulating the ERS pathway, which represents a promising strategy for treating hepatic fibrosis.
Asunto(s)
Endorribonucleasas , Células Estrelladas Hepáticas , Ratones , Animales , Células Estrelladas Hepáticas/metabolismo , Endorribonucleasas/metabolismo , Endorribonucleasas/farmacología , Endorribonucleasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/metabolismo , Estrés del Retículo Endoplásmico , Apoptosis , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismoRESUMEN
BACKGROUND: Serum lipids variations are closely related to the sepsis progression; however, their value for patients with pyogenic liver abscesses (PLA) has rarely been studied. We investigated the serum lipid level variations in patients with PLA and its predictive value to the disease. METHODS: The study included 328 patients with PLA hospitalized in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2021; 35 (10.67%) in the severe group (SG) and 293 (89.33%) in the non-severe group (nSG). Their clinical records were analyzed retrospectively, and dynamic curves were drawn to clarify the changes in different indicators during the course of the disease. RESULTS: High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a) (Lp(a)) in the SG were significantly lower than those in nSG (P < 0.001). Total cholesterol (TC) at baseline (OR = 0.184, P < 0.001) was an independent risk factor for severe patients and had the highest predictive value, with an area under the curve of 0.859 and a cut-off value of 2.70 mmol/L (sensitivity = 94.3%, specificity = 63.5%). For patients who met the criteria for drainage surgery, TC, HDL-C and LDL-C levels continued to decrease with antibiotic therapy alone before drainage and began to increase after the surgery. CONCLUSIONS: Low TC level on admission is an independent risk factor for the progression of severe illness in PLA patients, with the highest predictive value surpassing other routine clinical indices. Abscess drainage should be performed as soon as possible for patients whose TC continues to decline after medical treatment.
Asunto(s)
Colesterol , Absceso Piógeno Hepático , Humanos , Estudios Retrospectivos , LDL-Colesterol , Triglicéridos , Pronóstico , Relevancia Clínica , HDL-Colesterol , PoliésteresRESUMEN
Radiotherapy (RT) has been viewed as one of the most effective and extensively applied curatives in clinical cancer therapy. However, the radioresistance of tumor severely discounts the radiotherapy outcomes. Here, an innovative supramolecular radiotherapy strategy, based on the complexation of a hypoxia-responsive macrocycle with small-molecule radiosensitizer, is reported. To exemplify this tactic, a carboxylated azocalix[4]arene (CAC4A) is devised as molecular container to quantitatively package tumor sensitizer banoxantrone dihydrochloride (AQ4N) through reversible host-guest interaction. Benefited from the selective reduction of azo functional groups under hypoxic microenvironment, the supramolecular prodrug CAC4Aâ¢AQ4N exhibits high tumor accumulation and efficient cellular internalization, thereby significantly amplifying radiation-mediated tumor destruction without appreciable systemic toxicity. More importantly, this supramolecular radiotherapy strategy achieves an ultrahigh sensitizer enhancement ratio (SER) value of 2.349, which is the supreme among currently reported noncovalent-based radiosensitization approach. Further development by applying different radiosensitizing drugs can make this supramolecular strategy become a general platform for boosting therapeutic effect in cancer radiotherapies, tremendously promising for clinical translation.
Asunto(s)
Hipoxia , Compuestos Macrocíclicos/uso terapéutico , Neoplasias/radioterapia , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Línea Celular Tumoral , HumanosRESUMEN
Photothermal agents (PTAs) based on organic small-molecule dyes emerge as promising theranostic strategy in imaging and photothermal therapy (PTT). However, hydrophobicity, photodegradation, and low signal-to-noise ratio impede their transformation from bench to bedside. In this study, a novel supramolecular PTT formulation by a stimuli-responsive macrocyclic host is prepared to overcome these obstacles of organic small-molecule PTAs. Methods: Sulfonated azocalix[4]arene (SAC4A) was synthesized as a hypoxia-responsive macrocyclic host. Taking IR780 as an example, the supramolecular nanoformulation IR780@SAC4A was constructed by grinding method, and its solubility, photostability, and photothermal conversion were evaluated. The hypoxia tumor-selective imaging and supramolecular PTT of IR780@SAC4A were further evaluated in vitro and in vivo. Results: IR780@SAC4A is capable of enhancing the solubility, photostability, and photothermal conversion of IR780 significantly, which achieve this supramolecular formulation with good imaging-guided PTT efficacy in vitro and in vivo. Conclusions: This study demonstrates that the supramolecular PTT strategy is a promising cancer theranostic method. Moreover, this supramolecular approach is applicative to construct kinds of supramolecular PTAs, opening a general avenue for extending smart PTT formulations.
Asunto(s)
Hipoxia/metabolismo , Neoplasias/terapia , Fotoquimioterapia/métodos , Terapia Fototérmica/métodos , Nanomedicina Teranóstica/métodos , Animales , Línea Celular Tumoral , RatonesRESUMEN
The release of tumor-associated antigens (TAAs) and their cross-presentation in dendritic cells (DCs) are crucial for radio-immunotherapy. However, the irradiation resistance of tumor cells usually results in limited TAA generation and release. Importantly, TAAs internalized by DCs are easily degraded in lysosomes, resulting in unsatisfactory extent of TAA cross-presentation. Herein, an antigen-capturing stapled liposome (ACSL) with a robust structure and bioactive surface is developed. The ACSLs capture and transport TAAs from lysosomes to the cytoplasm in DCs, thereby enhancing TAA cross-presentation. l-arginine encapsulated in ACSLs induces robust T cell-dependent antitumor response and immune memory in 4T1 tumor-bearing mice after local irradiation, resulting in significant tumor suppression and an abscopal effect. Replacing l-arginine with radiosensitizers, photosensitizers, and photothermal agents may make ACSL a universal platform for the rapid development of various combinations of anticancer therapies.
Asunto(s)
Reactividad Cruzada , Liposomas , Animales , Antígenos de Neoplasias , Células Dendríticas , Inmunoterapia/métodos , Liposomas/metabolismo , RatonesRESUMEN
Increasing bacterial drug resistance to antibiotics has posed a major threat to contemporary public health, which resulted in a large number of people suffering from serious infections and ending up dying without any effective therapies every year. Here, a dynamic covalent polymeric antimicrobial, based on phenylboronic acid (PBA)-installed micellar nanocarriers incorporating clinical vancomycin and curcumin, is developed to overcome drug-resistant bacterial infections. The formation of this antimicrobial is facilitated by reversible dynamic covalent interactions between PBA moieties in polymeric micelles and diols in vancomycin, which impart favorable stability in blood circulation and excellent acid-responsiveness in the infection microenvironment. Moreover, the structurally similar aromatic vancomycin and curcumin molecules can afford π-π stacking interaction to realize simultaneous delivery and release of payloads. In comparison with monotherapy, this dynamic covalent polymeric antimicrobial demonstrated more significant eradication of drug-resistant bacteria in vitro and in vivo due to the synergism of the two drugs. Furthermore, the achieved combination therapy shows satisfied biocompatibility without unwanted toxicity. Considering various antibiotics contain diol and aromatic structures, this simple and robust strategy can become a universal platform to combat the ever-threatening drug-resistant infectious diseases.
RESUMEN
Background and Aims: Granulocyte colony-stimulating factor (G-CSF) has been proposed as a therapeutic option for patients with acute-on-chronic liver failure (ACLF). However, its clinical efficacy remains debatable. This study aimed to synthesize available evidence on the efficacy of G-CSF in ALCF. Methods: The Cochrane Library, CNKI, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched from inception until September 2021. After qualitative evaluation of the included literature, the included studies were analyzed. Results: Seven studies were included in this meta-analysis. Overall, G-CSF therapy was not associated with a reduced risk of death (30-day survival, OR = 1.55, 95% CI: 1.00, 2.38, P = 0.05; 60-day survival, OR = 1.50, 95% CI: 0.95, 2.36, P = 0.08; 90-day survival, OR = 1.61, 95% CI: 0.99, 2.62, P = 0.05) or complication including occurrence of infections infection (OR = 0.66, 95% CI: 0.41, 1.05, P = 0.08), bleeding (OR = 1.50, 95% CI: 0.58, 3.89, P = 0.41), and hepatorenal syndrome (OR = 0.56, 95% CI: 0.25, 1.24, P = 0.15). Moreover, it had no obvious beneficial effects on the model of end-stage liver disease score (30-day SMD = -3.31, 95%CI: -7.42, 0.81, P = 0.12; 60-day SMD = -1.23, 95% CI: -5.21, 2.75, P = 0.54; 90-day SMD = -2.29, 95%CI: -4.94, 0.37, P = 0.09). Sensitivity analyses showed that patients in Asia had improved survival (30-day OR = 2.76, 95%CI: 1.43, 5.35, P = 0.003; 60-day OR = 2.83, 95% CI: 1.39, 5.73, P = 0.004; 90-day OR = 2.92, 95% CI: 1.34, 6.36, P = 0.007). Conclusions: Our findings suggest that, currently, G-CSF cannot be recommended for the treatment of ACLF.
RESUMEN
NIR-activated therapies based on light-responsive drug delivery systems are emerging as a remote-controlled method for cancer precise therapy. In this work, fluorescent dye indocyanine green (ICG)-conjugated and bioactive compound gambogic acid (GA)-loaded polymeric micelles (GA@PEG-TK-ICG PMs) were smoothly fabricated via the self-assembly of the reactive oxygen species (ROS)-responsive thioketal (TK)-linked amphiphilic polymer poly(ethyleneglycol)-thioketal-(indocyanine green) (PEG-TK-ICG). The resultant micelles demonstrated increased resistance to photobleaching, enhanced photothermal conversion efficiency, NIR-controlled drug release behavior, preferable biocompatibility, and excellent tumor accumulation performance. Moreover, upon an 808 nm laser irradiation, the micellar photoactive chromophore ICG converted the absorbed optical energy to both hyperthermia for photothermal therapy (PTT) and ROS as the feedback trigger to the micelles for the tumor-specific release of GA, which could serve as not only a chemotherapeutic drug to directly kill tumor cells but also a heat shock protein 90 (HSP90) inhibitor to realize the photothermal sensitization. As a result, an extremely high tumor inhibition rate (97.9%) of mouse 4 T1 breast cancer models was achieved with negligible side effects after the chemo-photothermal synergistic therapy. This NIR-activated nanosystem with photothermal self-sensitization function may provide a feasible option for the effective treatment of aggressive breast cancers.
Asunto(s)
Hipertermia Inducida , Neoplasias , Animales , Línea Celular Tumoral , Verde de Indocianina , Ratones , Micelas , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , PolímerosRESUMEN
Radiotherapy (RT) combined with chemotherapy remains a dominant therapeutic manner in clinical tumor treatment, which is irreplaceable in a short term. To seek an intrinsic connection of combined chemoradiation therapy and maximize the antitumor efficacy, we developed a reactive oxygen species (ROS)-sensitive nanomicelle drug delivery system based on a self-assembled amphiphilic polymer, hyaluronic acid-graft-poly-(propylene sulfide) (HA-PPS). A chemical radiosensitizer, doxorubicin (DOX), was encapsulated into the core of HA-PPS nanomicelles, constituting the DOX-loaded nanomicelles (HA-PPS@DOX NMs) with a spherical structure of around 205.10 ± 11.33 nm diameter with a narrow polydispersity index (PDI) of 0.135 ± 0.01. When combined with RT, the ROS-sensitive HA-PPS@DOX NMs disintegrated and released great drug cargos, which further enhanced cytotoxicity. Meanwhile, as a radiosensitizer, the released DOX sensitized cancer cells to radiotherapy, which has been confirmed by an enhanced sensitizer enhancement ratio (SER) value of 1.78 contributing to the increased cytotoxicity of concurrent chemoradiation tumor therapy, as evidenced by the improvement of half maximal inhibitory concentration (IC50 value) of DOX from 2.316 to 0.8235 µg/mL. Moreover, in vivo studies revealed that HA-PPS@DOX NMs exhibited prolonged circulation time and improved tumor accumulation. Particularly, the released DOX triggered by radiation strengthened radiotherapy sensitization in return. Consequently, these superiorities of HA-PPS@DOX NMs shown by the concurrent chemoradiation tumor therapy resulted in an ideal tumor inhibition rate of 70.4%, thus providing a promising ROS-sensitive nanomedicine for cancer treatment.
RESUMEN
Human islet amyloid polypeptide (hIAPP) aggregation is closely associated with dysfunction and apoptosis of pancreatic ß-cells in type 2 diabetes (T2D). Accordingly, hIAPP amyloid inhibitors have shown promise against T2D. Here, by mimicking the function of natural molecular chaperones, nanochaperones (nChaps) based on self-assembled polymeric micelles with tunable surface microdomains for T2D treatment are reported. By capturing the aggregation-prone species of hIAPP onto the hydrophobic microdomains and segregating them by hydrophilic PEG chains, this kind of nChaps could effectively prevent hIAPP aggregation, block cell adhesion of hIAPP, facilitate hIAPP aggregates degradation and reduce hIAPP-related cytotoxicity. Therefore, our work will provide useful insights to develop a biomimetic strategy for the treatment of T2D.
Asunto(s)
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Apoptosis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Polipéptido Amiloide de los Islotes Pancreáticos/químicaRESUMEN
Drug-resistant bacterial infections have stolen the spotlight in recent years as stubborn diseases intimidating public health, thus urgently requiring the development of innovative treatment strategies with high antibacterial efficiency and low bacterial resistance. Here, a polymeric antimicrobial with synergistic chemo-photodynamic therapy function is fabricated to combat drug-resistant bacterial infections. In this strategy, polymeric micelles based on amphiphilic poly(aspartic acid)-block-poly(ε-caprolactone) (PAsp-b-PCL) are used as nanocarriers to encapsulate a photosensitizer protoporphyrin IX (PpIX) in the micellar core, which then undergo silver nanoparticle decoration on the micellar shell through an in situ reduction method. Compared with mono-therapy, the combination of silver nanoparticle decoration and light-activatable PpIX enables the resulting polymeric antimicrobial to exert chemo-photodynamic activity to kill drug-resistant bacteria more potently in vitro. Furthermore, the prepared polymeric antimicrobials with synergistic antibacterial activity show robust eradication efficacy against subcutaneous infections induced by drug-resistant Staphylococcus aureus in a murine model. Therefore, our study provides a simple and potent strategy to realize combination therapy for eradicating drug-resistant bacterial infections.
Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Staphylococcus aureus Resistente a Meticilina , Fotoquimioterapia , Animales , Ratones , Micelas , PlataRESUMEN
We constructed a novel supramolecular hydrogel by carrying out a coassembly of cisplatin and short naproxen-capped peptides. This procedure boosted the radiosensitization effect of cisplatin by increasing the number of Pt-DNA adducts, arresting the cell cycle, and inhibiting cyclooxygenase-2.
Asunto(s)
Antineoplásicos/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Ciclooxigenasa 2/metabolismo , Hidrogeles/química , Péptidos/química , Fármacos Sensibilizantes a Radiaciones/farmacología , Células A549 , Antineoplásicos/química , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Fármacos Sensibilizantes a Radiaciones/químicaRESUMEN
Novel nanocomposite of Ag/AgCl and a single phase of anhydrous basic bismuth nitrate (ABBN)-Bi6O4.46(OH)3.54(NO3)5.54 with efficient antibacterial activity was prepared from BiOCl. Microstructure was characterized as AgCl nanotubes and Ag nanoparticles mixed with Bi6O4.46(OH)3.54(NO3)5.54 nanosheets in nanometer scale. Antibacterial activity of the composite was tested by agar disc diffusion and agar dilution methods using Escherichia coli as target bacteria. The diameter of inhibition zone of Ag/AgCl/ABBN is 17.0â¯mm while that of bulk BBN is 8.1â¯mm. The MIC value of Ag/AgCl/ABBN is ascertained as 35⯵gâ¯mL-1. Results prove that Ag/AgCl/ABBN nanocomposite has much higher antibacterial activity in comparison with bulk basic bismuth nitrate.