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The development of cities and regions emerges from the complex associations at various spatial levels, highlighting the importance of a multi-scale approach to analyzing regional urban networks. This study attempts to establish a new analysis framework encompassing national, regional, and local dimensions by employing a population flow network in the Yangtze River Delta in China. It explores the inter-city connections and spatial structures of regional urban networks as well as the correlations and differentiations of urban functions under multi-scale interaction. The results indicate that: (1) Regional network demonstrates notable multi-scale interactions with an explicit hierarchical structure; (2) The roles and positions of different cities vary significantly across scales due to economic, administrative, locational, and transportation differences; (3) Different city types can drive their evolution by navigating through rescaling in a diverse multi-scale environment; (4) A positive correlation is observed when comparing the functional behaviors of cities across various scales. This study provides insights for cities to identify their strategic roles and adapt development strategies within the wider network framework, offering theoretical and practical contributions to multi-scale urban networks analysis.
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Soybean phospholipid was used as an amphiphilic material to form reverse micelles (RMs) in medium glycerol monolinoleate (Maisine) with Exenatide (EXT.) encapsulated in the polar core formed by the hydrophilic part of phospholipid. Cremopher RH40 and caprylocaproyl macrogol-8 glycerides EP/caprylocaproyl polyoxyl-8 glycerides NF (Labrasol) were added as surfactants to prepare reverse micelles-self emulsifying drug delivery system (RMs-SEDDS). On this basis, oil in water (O/W) emulsion was further prepared. By adding DOTAP, the surface of the emulsion was positively charged. Finally, hyaluronic acid wrapping in the outermost layer by electrostatic adsorption and reverse micelles-O/W-sodium hyaluronate (RMs-O/W-HA) nanoparticles containing Exenatide were prepared. RMs-SEDDS was spherical with an average particle size of 213.6 nm and RMs-O/W-HA was double-layered spherical nanoparticle with an average particle size of 309.2 nm. HA coating enhanced the adhesion of nanoparticles (NPs), and RMs-O/W-HA increased cellular uptake through CD44-mediated endocytosis. Pharmacodynamics results showed that RMs-SEDDS and RMs-O/W-HA could reduce blood glucose in type 2 diabetic rats, protect pancreatic ß cells to a certain extent, and relieve insulin resistance and hyperlipemia complications with good safety.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Nanopartículas , Ratas , Animales , Micelas , Ácido Hialurónico , Exenatida , Emulsiones , Diabetes Mellitus Experimental/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Glicéridos , FosfolípidosRESUMEN
Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD-integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy.
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Boranos , Terapia por Captura de Neutrón de Boro , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/radioterapia , Terapia por Captura de Neutrón de Boro/métodos , Boro , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/radioterapia , Oligosacáridos , Línea Celular TumoralRESUMEN
The gasification fly ash (GFA), a bulk industrial solid waste from coal gasification process, urgently needs to be effectively disposed. In order to use the GFA as porous carbon materials, fluidized activation experiments of the GFA from an industrial circulating fluidized bed (CFB) gasifier were conducted in a bench-scale CFB test rig, as well as steam activation experiments of GFA in a vertical tube furnace and theoretical analysis on the activation process. Due to the ultrafine particle size, the GFA faces a fluidization problem and auxiliary particles are needed to stabilize its fluidization. In the fluidized activation, the pore structure of GFA particles becomes developed in a seconds-level time (about 1.5 s). The specific surface area (SBET) of activated GFA increases with temperature, maximally increasing by 48.9 % and reaching 204 m2/g. Steam activation experiments show that the GFA has an activation potential of 362 m2/g (SBET) and the pore structure evolution of GFA can be quantified by carbon conversion ratio. Based on this, the fluidized activation of GFA is found in the stage of pore development. By appropriately increasing the carbon conversion ratio (below 40 %), the fluidized activation effect of GFA is expected to be improved. Theoretical analysis indicates for the GFA the features of ultra-fine particle size and well-developed pore structure greatly enhance the diffusion rate of active component into the particles. Under the strong diffusion effect, increasing temperature is a critical means to realize the rapid and effective activation of GFA in a finite time.
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Ceniza del Carbón , Vapor , Carbón Mineral , Carbono/química , Temperatura , Residuos IndustrialesRESUMEN
Inefficient tumor penetration caused by the characteristics of tumor microenvironments is a primary obstacle to improving drug delivery efficiency, which restricts the chemotherapy drug efficacy. One such promising idea is to construct micro/nanomotors (MNMs) as an effective delivery vehicle by way of producing autonomous motion and converting exogenous stimuli or external energies from the surrounding environment into mechanical forces. In this research, the Pt/DOX nanomotor was prepared, and the enhanced diffusion and positive chemotaxis driven by substrates were verified in vitro, proof of the enhanced cellular uptake and deep penetration of Pt/DOX. As a novel nanovehicle, Pt/DOX potentially provides an intriguing approach to foster the tumor-deep penetration and enhance the drug delivery efficiency.
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Nanopartículas , Neoplasias , Quimiotaxis , Doxorrubicina , Sistemas de Liberación de Medicamentos , Humanos , Movimiento (Física) , Neoplasias/tratamiento farmacológico , Microambiente TumoralRESUMEN
Phagocytosis checkpoints, especially targeting CD47, have shown encouraging therapeutic effects. However, there are currently many shortcomings and challenges with immune checkpoint blockades (ICBs). Inspired by the phenomenon of molecular self-assembly, we modify the CD47 targeting peptide (4N1K) onto the self-assembled peptide FY4, as well as the concatenation of PEG at the other terminal via the AZO group to construct hypoxia-responsive nanoparticles (PEG-AZO-FY4-4N1K, PAP NPs), utilizing the peptide as a part of the anti-tumor therapy machine. After degradation, PAP NPs can self-assemble to form fibrous networks and anchor CD47 on the surface of tumor cells, promoting their recognition and phagocytosis by macrophages and relieving immune escape. Self-assembled peptides can interweave on the surface of tumor cells, fully exploiting their morphological advantages to impede normal cell interaction and metastasis. The PAP NPs work synergistically with Doxorubicin (DOX) to further maximize the efficacy of chemoimmunotherapy. In conclusion, this strategy pioneers the progress of self-assembled peptides in biomedicine and promises a novel breakthrough in the development of checkpoint inhibitor therapies.
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Nanopartículas , Neoplasias , Antígeno CD47 , Humanos , Inmunoterapia , Nanopartículas/química , Neoplasias/patología , Péptidos/farmacología , Péptidos/uso terapéutico , FagocitosisRESUMEN
In previous studies, we found that triphenylphosphine-modified doxorubicin (TPP-DOX) can effectively kill drug-resistant tumor cells, but its effect on sensitive tumor cells is weakened. In this research, with albumin from Bovine Serum (BSA) as a carrier, TPP-DOX@MnBSA (TD@MB) nanoparticles were prepared by co-loading TPP-DOX and manganese which can realize the combination of chemotherapy and chemodynamic therapy (CDT). The uniform and stable nano-spherical nanoparticle can promote drug uptake, achieve mitochondrial-targeted drug delivery, increase intracellular reactive oxygen species (ROS) and catalyze the production of highly toxic oxidative hydroxyl radicals (OH·), further inhibiting the growth of both sensitive and drug-resistant MCF-7 cells. Besides, TD@MB can down-regulate the stemness-related proteins and the metastasis-related proteins, potentially decreasing the tumor stemness and metastasis. In vivo experiment indicated that TD@MB was able to exert desired antitumor effect, good tumor targeting and biocompatibility.
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Neoplasias de la Mama , Nanopartículas , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Catálisis , Línea Celular Tumoral , Doxorrubicina , Femenino , Humanos , Células MCF-7 , Manganeso/uso terapéutico , Nanopartículas/uso terapéuticoRESUMEN
There is evidence to suggest that the primary tumor induces the formation of a pre-metastatic niche in distal organs by stimulating the production of pro-metastatic factors. Given the fundamental role of the pre-metastatic niche in the development of metastases, interruption of its formation would be a promising strategy to take early action against tumor metastasis. Here we report an enzyme-activated assembled peptide FR17 that can serve as a "flame-retarding blanket" in the pre-metastatic niche specifically to extinguish the "fire" of tumor-supportive microenvironment adaption. We show that the in-situ assembled peptide nano-blanket inhibits fibroblasts activation, suppressing the remodeling of the metastasis-supportive host stromal tissue, and reversing vascular destabilization and angiogenesis. Furthermore, we demonstrate that the nano-blanket prevents the recruitment of myeloid cells to the pre-metastatic niche, regulating the immune-suppressive microenvironment. We show that FR17 administration effectively inhibits the formation of the pulmonary pre-metastatic niche and postoperative metastasis, offering a therapeutic strategy against pre-metastatic niche formation.
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Neoplasias , Fibroblastos/patología , Humanos , Pulmón/patología , Metástasis de la Neoplasia/patología , Neoplasias/patología , Péptidos/farmacología , Microambiente TumoralRESUMEN
Glioblastoma is the most common brain primary malignant tumor with the highest mortality. Boron neutron capture therapy (BNCT) can efficiently kill cancer cells on the cellular scale, with high accuracy, short course and low side-effects, which is regarded as the most promising therapy for malignant brain tumors like glioma. As the keypoint of BNCT, all boron delivery agents currently in clinical use are beset by insufficient tumor uptake, especially in the tumor nucleus, which limits the clinical application of BNCT. In this study, nuclear targeting of boron is achieved by DOX-CB, consisting of doxorubicin (DOX) and carborane (CB) utilizing the nuclear translocation property of DOX. The nucleus of GL261 cells takes up almost three times the concentration of boron required for BNCT. To further kill glioma and inhibit recurrence, a new multifunctional nanoliposome delivery system DOX-CB@lipo-pDNA-iRGD is constructed. It combines DOX-CB with immunotherapy strategy of blocking macrophage immune checkpoint pathway CD47-SIRPα by CRISPR-Cas9 system, coupling BNCT with immunotherapy simultaneously. Compared with clinical drug Borocaptate Sodium (BSH), DOX-CB@lipo-pDNA-iRGD significantly enhances the survival rate of tumor-bearing mice, reduces tumor stemness, and improves the prognosis. The excellent curative effect of this nanoliposome delivery system provides an insight into the combined treatment of BNCT.
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Terapia por Captura de Neutrón de Boro , Neoplasias Encefálicas , Glioblastoma , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/metabolismo , Antígeno CD47/genética , Edición Génica , Glioblastoma/tratamiento farmacológico , Ratones , Preparaciones FarmacéuticasRESUMEN
Background: This study aimed to evaluate the impact of patients' positioning before and after intubation with mechanical ventilation, and after extubation on the lung function and blood oxygenation of patients with morbid obesity, who had a laparoscopic sleeve gastrectomy. Methods: Patients with morbid obesity (BMI ≥ 30 kg/m2, ASA I - II grade) who underwent laparoscopic sleeve gastrectomy at our hospital from June 2018 to January 2019 were enrolled in this prospective study. Before intubation, after intubation with mechanical ventilation, and after extubation, arterial blood was collected for blood oxygenation and gas analysis after posturing the patients at supine position or 30° reverse Trendelenburg position (30°-RTP). Results: A total of 15 patients with morbid obesity were enrolled in this self-compared study. Pulmonary shunt (Qs/Qt) after extubation was significantly lower at 30°-RTP (18.82 ± 3.60%) compared to that at supine position (17.13 ± 3.10%, p < 0.01). Patients' static lung compliance (Cstat), during mechanical ventilation, was significantly improved at 30°-RTP (36.8 ± 6.7) compared to that of those in a supine position (33.8 ± 7.3, p < 0.05). The PaO2 and oxygen index (OI) before and after intubation with mechanical ventilation were significantly higher at 30°-RTP compared to that at supine position, and in contrast, the PA-aO2 before and after intubation with mechanical ventilation was significantly reduced at 30°-RTP compared to that at supine position. Conclusion: During and after laparoscopic sleeve gastrectomy, patients with morbid obesity had improved lung function, reduced pulmonary shunt, reduced PA-aO2 difference, and increased PaO2 and oxygen index at 30°-RTP compared to that supine position.
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Boron neutron capture therapy (BNCT) is a selective biological targeted nuclide technique for cancer therapy. It has the following attractive features: good targeting, high effectiveness, and causes slight damage to surrounding healthy tissue compared with other traditional methods. It has been considered as one of the promising methods for the treatment of various cancers. Measuring 10B concentrations is vital for BNCT. However, the existing technology and equipment cannot satisfy the real-time and accurate measurement requirements, and more efficient methods are in demand. The development of methods and imaging applied in BNCT to help measure boron concentration is described in this review.
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Terapia por Captura de Neutrón de Boro , Boro , Compuestos de Boro , Terapia por Captura de Neutrón de Boro/métodos , Diagnóstico por ImagenRESUMEN
RATIONALE: Cis-atracurium as an intermediate-acting non-depolarizing neuromuscular blocker is widely used clinically with less causing cyclic fluctuations and less histamine release. As the use rate increases, allergic reactions and anaphylactoid reactions caused by cis-atracurium increase. PATIENT CONCERNS: A 23-year-old woman underwent laparoscopic bariatric surgery. Airway spasm occurred after anesthesia induction and the operation was suspended. After adjustment, the anesthesia was performed with the same anesthetic scheme again. After induction, skin flushing and airway resistance increased, then the symptoms were relieved. When the cis-atracurium was given again, the symptoms of airway spasm reappeared immediately, and after communicating with the family, the operation was successfully completed with rocuronium. DIAGNOSES: Serious bronchospasm induced by cisatracurium besylate. INTERVENTIONS: The patient was undergone assisted ventilation with continuous positive airway pressure (CPAP) and aminophylline 250âmg, methylprednisolone 80âmg were given intravenously. OUTCOMES: There was no any obvious discomfort in the patient's self-report during the next day's visit. The patient was discharged 7âdays later. No abnormalities were observed during following 4âweeks. LESSONS: Although the anaphylactoid reactions caused by cis-atracurium are rare, the bronchospasm and anaphylactic shock caused by it greatly increase the risk of anesthesia, which should be taken seriously by clinicians. Increased vigilance in diagnosis, and treatment are essential to prevent aggravation and further complication.
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Anafilaxia/inducido químicamente , Anestesia General/efectos adversos , Atracurio/análogos & derivados , Espasmo Bronquial/inducido químicamente , Bloqueantes Neuromusculares/efectos adversos , Atracurio/efectos adversos , Cirugía Bariátrica , Femenino , Humanos , Laparoscopía , Adulto JovenRESUMEN
Macrophages have a leading position in the tumor microenvironment (TME) which paves the way to carcinogenesis. Initially, monocytes and macrophages are recruited to the sites where the tumor develops. Under the guidance of different microenvironmental signals, macrophages would polarize into two functional phenotypes, named as classically activated macrophages (M1) and alternatively activated macrophages (M2). Contrary to the anti-tumor effect of M1, M2 exerts anti-inflammatory and tumorigenic characters. In progressive tumor, M2 tumor-associated macrophages (TAMs) are in the majority, being vital regulators reacting upon TME. This review elaborates on the role of TAMs in tumor progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only in clinical trials but also at primary research stages, are summarized followed by a discussion about their clinical application values. Nanoparticulate systems with efficient drug delivery and improved antitumor effect are also summed up in this article.
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Metastasis is the primary cause of death for most cancer patients, in which tumor-associated macrophages (TAMs) are involved through several mechanisms. While hitherto there is still a lack of study on exclusive elimination of TAMs to inhibit metastasis due to the difficulties in specific targeting of TAMs, we construct an extra- and intracellular stepwise-responsive delivery system p-(aminomethyl)benzoic acid (PAMB)/doxorubicin (DOX) to achieve specific TAM depletion for the first time, thereby preventing tumor metastasis. Once accumulated into the tumor, PAMB/DOX would stepwise responsively (hypoxia and reactive oxygen species (ROS) responsively) disintegrate to expose the TAM-targeting ligand and release DOX sequentially, which depletes TAMs effectively in vivo. Owing to the inhibition of extracellular matrix (ECM) degradation, neovascularization, and tumor invasion contributed by TAM depletion, lung metastasis was successfully inhibited. Furthermore, PAMB/DOX showed efficient inhibition against tumor growth as well as spontaneous metastasis formation when combined with additional chemotherapy, representing a safe and efficient nanoplatform to modulate the adverse tumor microenvironment via TAM elimination.
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Portadores de Fármacos/química , Espacio Extracelular/efectos de los fármacos , Espacio Intracelular/efectos de los fármacos , Nanoestructuras/química , Macrófagos Asociados a Tumores/efectos de los fármacos , para-Aminobenzoatos/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacología , Liberación de Fármacos , Espacio Extracelular/metabolismo , Espacio Intracelular/metabolismo , Ratones , Metástasis de la Neoplasia , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Distribución Tisular , Hipoxia Tumoral/efectos de los fármacos , Macrófagos Asociados a Tumores/patología , para-Aminobenzoatos/farmacocinéticaRESUMEN
Nitrogen mustard (NM) is among the earliest drugs used to treat malignant tumors and it kills tumor cells by cross-linking DNA. Unfortunately, because of the short half-life and unfavorable selectivity, NM causes significant damage to normal tissues. As NM can increase the levels of reactive oxygen species (ROS) in tumor cells, a ROS-activated nitrogen mustard prodrug (NM-Pro) was synthesized and mixed with NM at a specific ratio to obtain an "NM-ROS-NM-Pro-NM" positive feedback system, which ultimately achieves a specific lethal effect on hematological neoplasms. The further encapsulation of NM/NM-Pro in liposomes allows the sustained release of the drug and prolongs the residence time in vivo. Here, we prepared stable liposomes with a uniform particle size of 170.6 ± 2.2 nm. The optimal ratio of NM to NM-Pro in this study was 2:1. The active drug NM in the NM/NM-Pro system continuously stimulated ROS production by the cells, which in turn further activated the NM-Pro to continuously generate NM. The positive feedback pathway between the NM and NM-Pro resulted in the specific death of tumor cells. Furthermore, the K562 hematological neoplasm model was utilized to evaluate the therapeutic effect of NM/NM-Pro liposomes in vivo. After encapsulation in liposomes, the targeting of tumor cells was increased approximately two times compared with that of normal cells, and NM/NM-Pro liposomes exhibited reduced toxicity, without an increase in drug activity compared to the NM/NM-Pro combination. The NM/NM-Pro delivery system exerts a positive feedback effect on ROS production in tumor cells and displays good potential for the specific killing of hematoma cells.
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Antineoplásicos Alquilantes/administración & dosificación , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Retroalimentación Fisiológica , Neoplasias Hematológicas/tratamiento farmacológico , Mecloretamina/administración & dosificación , Profármacos/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Animales , Antineoplásicos Alquilantes/farmacocinética , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Liberación de Fármacos , Femenino , Humanos , Células K562 , Liposomas , Mecloretamina/farmacocinética , Ratones , Tamaño de la Partícula , Profármacos/farmacocinética , Ratas , Ratas Sprague-Dawley , Resultado del TratamientoRESUMEN
Self-assembled peptide nanofibers have been widely studied in cancer nanotherapeutics with their excellent biocompatibility and low toxicity of degradation products, showing the significant potential in inhibiting tumor progression. However, poor solubility prevents direct intravenous administration of nanofibers. Although water-soluble peptide precursors have been formed via the method of phosphorylation for intravenous administration, their opportunities for broad in vivo application are limited by the weak capacity of encapsulating drugs. Herein, we designed a novel restructured reduced glutathione (GSH)-responsive drug delivery system encapsulating doxorubicin for systemic administration, which achieved the intracellular restructuration from three-dimensional micelles into one-dimensional nanofibers. After a long blood circulation, micelles endocytosed by tumor cells could degrade in response to high GSH levels, achieving more release and accumulation of doxorubicin at desired sites. Further, the synergistic chemotherapy effects of self-assembled nanofibers were confirmed in both in vitro and in vivo experiments.
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Doxorrubicina/administración & dosificación , Portadores de Fármacos/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Glutatión/metabolismo , Nanofibras/química , Células A549 , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/farmacocinética , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Sinergismo Farmacológico , Endocitosis/efectos de los fármacos , Glutatión/sangre , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ratones Endogámicos BALB C , Micelas , Péptidos/química , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
PURPOSE: Boron neutron capture therapy (BNCT) is an emerging binary radiotherapy, which is limited for application due to the challenge of targeted delivery into tumor nowadays. Here, we propose the use of iRGD-modified polymeric nanoparticles for active targeted delivery of boron and doxorubicin (DOX) in BNCT. METHODS: 10B-enriched BSH was covalently grafted to PEG-PCCL to prepare 10B-polymer, then surface-modified with iRGD. And, DOX was physically incorporated into polymers afterwards. Characterization of prepared polymers and in vitro release profile of DOX from polymers were determined by several methods. Cellular uptake of DOX was observed by confocal microscope. Accumulation of boron in cells and tissues was analyzed by ICP-MS. Biodistribution of DOX was studied by ex vivo fluorescence imaging and quantitative measurement. Tumor vascular normalization of Endostar for promoting delivery efficiency of boron on refractory B16F10 tumor was also studied. RESULTS: The polymers were monodisperse and spheroidal in water with an average diameter of 24.97 nm, which were relatively stable at physiological pH and showed a sustained release of DOX, especially at endolysosomal pH. Enhanced cellular delivery of DOX was found in iRGD-modified polymer group. Cellular boron uptake of iRGD-modified polymers in A549 cells was remarkably raised fivefold (209.83 ng 10B/106 cells) compared with BSH. The polymers represented prolonged blood circulation, enhanced tumor accumulation of 10B against BSH, and favorable tumor:normal tissue boron concentration ratios (tumor:blood = 14.11, tumor:muscle = 19.49) in A549 tumor-bearing mice 24 hrs after injection. Both fluorescence imaging and quantitative measurement showed the highest tumor accumulation of DOX at 24 hrs after injecting of iRGD-modified polymers. Improvement of vascular integrity and reduction of vascular mimicries were found after Endostar injection, and raised tumor accumulation of boron as well. CONCLUSION: The developed nanoparticle is an inspiring candidate for the safe clinical application for BNCT.
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Terapia por Captura de Neutrón de Boro , Boro/administración & dosificación , Nanopartículas/química , Oligopéptidos/química , Polímeros/química , Animales , Borohidruros/farmacocinética , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Liberación de Fármacos , Endocitosis/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Integrinas/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/irrigación sanguínea , Neoplasias/tratamiento farmacológico , Polímeros/síntesis química , Conejos , Compuestos de Sulfhidrilo/farmacocinética , Distribución Tisular , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Objective: This study was aimed to develop DOX-TPP loaded acetal-PEG-PCCL micelles to improve the clinical efficacy of drug resistance tumor. Significance: Chemotherapy is one of the main treatments for breast cancer but is plagued by multidrug resistance (MDR). DOX-TPP-loaded micelles can enhance the specific concentration of drugs in the tumor and improve the efficacy and overcome MDR. Methods: In this study, DOX-TPP-loaded micelles based on acetal-PEG-PCCL were prepared and their physicochemical properties were characterized. The cellular uptake and ability to induce apoptosis of the micelles was confirmed by flow cytometry in MCF-7/ADR cells. In addition, cytotoxicity of the micelles was studied in MCF-7 cells and MCF-7/ADR cells. Confocal is used to study the subcellular distribution of DOX. Free DOX-TPP or DOX-TPP-loaded acetal-PEG-PCCL micelles were administered via intravenous injection in the tail vain for the biodistribution study in vivo. Results: The diameter of micelles was about 102.4 nm and their drug-loading efficiency is 61.8%. The structural characterization was confirmed by 1H NMR. The micelles exhibited better antitumor efficacy compared to free doxorubicin in MCF-7/ADR cells by MTT assay. The apoptotic rate and the cellular uptake of micelles were significantly higher than free DOX and DOX-TPP. Micelles can efficiently deliver mitochondria-targeting DOX-TPP to tumor cells. The result of bio-distribution showed that the micelles had stronger tumor infiltration ability than free drugs. Conclusions: In this study, mitochondriotropic DOX-TPP was conjugated to the nanocarrier acetal-PEG-PCCL via ionic interaction to form a polymer, which spontaneously formed spherical micelles. The cytotoxicity and cellular uptake of the micelles are superior to free DOX and exhibit mitochondrial targeting and passive tumor targeting, indicating that they have potential prospects.
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Antineoplásicos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Nanoconjugados/química , Compuestos Organofosforados/administración & dosificación , Acetales/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/patología , Doxorrubicina/análogos & derivados , Doxorrubicina/farmacocinética , Composición de Medicamentos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Humanos , Células MCF-7 , Micelas , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Compuestos Organofosforados/química , Compuestos Organofosforados/farmacocinética , Poliésteres/química , Polietilenglicoles/química , Distribución TisularRESUMEN
Blending sewage sludge (SS) with Zhundong coal (ZDC) for combustion in coal-fired power plants is a recent approach that can alleviate the shortage of high-quality coal resources and achieve the harmless treatment of SS, while also having a significant influence on combustion and ash slagging. Due to the high content of alkali and alkaline earth metals (AAEMs) in ZDC, its combustion ash has a strong likelihood of slagging. This study aims to investigate the effect of blending SS with ZDC on combustion and ash slagging. Thermogravimetry (TG) results indicate that blending with SS could lower the ignition and burnout temperatures of ZDC. With an increase in the ratio of sludge, the comprehensive combustion index (S) first increases and then decreases, showing that blending SS with ZDC in an appropriate proportion could improve the overall combustion. Through the analysis of the interaction, it is confirmed that SS and ZDC could complement each other during co-combustion due to their different components. X-ray fluorescence (XRF) was used to test the ash components of different blending ratios (10-30%) and combustion temperatures (800-1100 °C). Slagging indices including alkali acid ratio (B/A), silicon ratio (G), and silica-alumina ratio (SiO2/Al2O3) were also calculated. The results suggest that the slagging behavior of ZDC is greatly reduced even if the blending ratio is only 10%. However, with an increase in the blending ratio, the effect on slagging gradually weakens. Considering the dual influence of SS blending on combustion and slagging, this study assumes the optimal blending ratio of 20%. Influenced by the components of the combustion ash, B/A and SiO2/Al2O3 are more suitable for evaluating the slagging tendency of ash; however, there is great deviation in the results for G. This research is beneficial to coal-fired power plants for the selection of operation parameters during co-combustion with SS.
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The PET and CT fusion image, combining the anatomical and functional information, has important clinical meaning. An effective registration of PET and CT images is the basis of image fusion. This paper presents a multithread registration method based on contour point cloud for 3D whole-body PET and CT images. Firstly, a geometric feature-based segmentation (GFS) method and a dynamic threshold denoising (DTD) method are creatively proposed to preprocess CT and PET images, respectively. Next, a new automated trunk slices extraction method is presented for extracting feature point clouds. Finally, the multithread Iterative Closet Point is adopted to drive an affine transform. We compare our method with a multiresolution registration method based on Mattes Mutual Information on 13 pairs (246~286 slices per pair) of 3D whole-body PET and CT data. Experimental results demonstrate the registration effectiveness of our method with lower negative normalization correlation (NC = -0.933) on feature images and less Euclidean distance error (ED = 2.826) on landmark points, outperforming the source data (NC = -0.496, ED = 25.847) and the compared method (NC = -0.614, ED = 16.085). Moreover, our method is about ten times faster than the compared one.