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1.
Small ; 19(35): e2301981, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37186376

RESUMEN

Poly-L-lactide (PLLA) offers a unique possibility for processing into biocompatible, biodegradable, and implantable piezoelectric structures. With such properties, PLLA has potential to be used as an advanced tool for mimicking biophysical processes that naturally occur during the self-repair of wounds and damaged tissues, including electrostimulated regeneration. The piezoelectricity of PLLA strongly depends on the possibility of controlling its crystallinity and molecular orientation. Here, it is shown that modifying PLLA with a small amount (1 wt%) of crystalline filler particles with a high aspect ratio, which act as nucleating agents during drawing-induced crystallization, promotes the formation of highly crystalline and oriented PLLA structures. This increases their piezoelectricity, and the filler-modified PLLA films provide a 20-fold larger voltage output than nonmodified PLLA during ultrasound (US)-assisted activation. With 99% PLLA content, the ability of the films to produce reactive oxygen species (ROS) and increase the local temperature during interactions with US is shown to be very low. US-assisted piezostimulation of adherent cells directly attach to their surface (such as skin keratinocytes), stimulate cytoskeleton formation, and as a result cells elongate and orient themselves in a specific direction that align with the direction of PLLA film drawing and PLLA dipole orientation.


Asunto(s)
Materiales Biocompatibles , Poliésteres , Materiales Biocompatibles/química , Poliésteres/química , Temperatura , Cristalización
2.
Nano Lett ; 22(7): 3141-3150, 2022 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-35318846

RESUMEN

The pivotal factors affecting the survival rate of patients include metastasis and tumor recurrence after the resection of the primary tumor. Anti-PD-L1 antibody (aPD-L1) has promising efficacy but with some side effects for the off-target binding between aPD-L1 and normal tissues. Here, inspired by the excellent targeting capability of platelets with respect to tumor cells, we propose bioengineered platelets (PDNGs) with inner-loaded doxorubicin (DOX) and outer-anchored aPD-L1-cross-linked nanogels to reduce tumor relapse and metastatic spread postoperation. The cargo does not impair the normal physiological functions of platelets. Free aPD-L1 is cross-linked to form nanogels with a higher drug-loading efficiency and is sustainably released to trigger the T-cell-mediated destruction of tumor cells, reversing the tumor immunosuppressive microenvironment. PDNGs can reduce the postoperative tumor recurrence and metastasis rate, prolonging the survival time of mice. Our findings indicate that bioengineered platelets are promising in postsurgical cancer treatment by the tumor-capturing and in situ microvesicle-secreting capabilities of platelets.


Asunto(s)
Plaquetas , Melanoma , Animales , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Inmunoterapia/métodos , Melanoma/tratamiento farmacológico , Ratones , Nanogeles , Recurrencia Local de Neoplasia , Microambiente Tumoral
3.
BMC Oral Health ; 22(1): 328, 2022 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-35941612

RESUMEN

OBJECTIVE: This study aimed to evaluate timing of fixation to retard bone absorption using finite element analysis(FEA). METHODS: Volunteer CT images were used to construct four models of mandibles with varying degrees of alveolar bone resorption. By simulating occlusal force loading, biomechanical analysis was made on the periodontal membrane, tooth root and surrounding bone (both cancellous and cortical) of mandibular dentition. RESULTS: The von Mises stress value of the periodontal structures was positively related with the degree of alveolar bone resorption, and the von Mises stress at the interface between the periodontal membrane and tooth root was increased significantly in moderate to severe periodontitis models. The von Mises stress at the interface between the periodontal cortical bone and cancellous bone was increased significantly in the severe periodontitis model. And the von Mises stress value with oblique loading showed significantly higher than vertical loading. CONCLUSION: Teeth with moderate to severe periodontitis, loosened tooth fixation can be used to retard bone absorption.


Asunto(s)
Pérdida de Hueso Alveolar , Periodontitis , Raíz del Diente , Pérdida de Hueso Alveolar/diagnóstico por imagen , Análisis del Estrés Dental , Análisis de Elementos Finitos , Humanos , Imagenología Tridimensional , Mandíbula , Estrés Mecánico , Raíz del Diente/cirugía
4.
J Sci Food Agric ; 101(3): 907-917, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32737882

RESUMEN

BACKGROUND: Efficient utilization of dietary fibers (DFs) is important for optimizing feed resource utilization and animal health. The aim of the current study was to assess the effects of DFs with varying physicochemical properties (bulky, viscous, and fermentable) on fermentation kinetics and microbial composition during in vitro fermentation by fecal inoculum from lactating sow. According to the physicochemical properties, three different DFs, lignocellulose (LC), modified cassava starch (MCS) and konjac flour (KF) were selected as bulky fiber, fermentable fiber and viscous fiber respectively. Gas production, short-chain fatty acids (SCFAs) profiles and microbial composition were monitored during the fermentation. RESULTS: Results showed that the gas production in 72 h (GP72h ) ranked as: KF > MCS > LC (P < 0.05). The halftime of asymptotic gas production ranked as: KF < MCS = LC (P < 0.001). At 36 h of fermentation, MCS group showed higher concentrations of formic acid and lactate than LC and KF groups, whereas KF group showed higher concentrations of propionate and butyrate than LC and MCS groups (P < 0.05). At 72 h of fermentation, KF group showed higher concentrations of formic acid, lactate and propionate than LC and MCS groups, whereas MCS group showed higher concentrations of acetate and butyrate than LC and KF groups (P < 0.05). At 36 h of fermentation, Anaerovibrio and Erysipelatoclostridium abundances were higher in KF group, whereas Proteiniclasticum abundance was higher in MCS group. At 72 h of fermentation, the abundance of Fibrobacter in LC group was higher than that in MCS and KF groups. In addition, we also observed that the abundances of certain specific bacteria (Anaerovibrio and Erysipelatoclostridium) were closely related to the SCFAs production (propionate and butyrate) at different fermentation times. CONCLUSION: Collectively, the present study revealed that KF is a fast fermentation fiber which could produce propionate and butyrate rapidly, whereas LC is difficult to be fermented by bacteria. In addition, the fermentation of DFs with different physicochemical properties had divergent impacts on microbial composition and SCFA production. These findings deepen our understanding of the mechanisms of interaction between DFs and intestinal microbiota, and provide new ideas for the rational use of fiber resources in lactating sows. © 2020 Society of Chemical Industry.


Asunto(s)
Bacterias/metabolismo , Fibras de la Dieta/metabolismo , Heces/microbiología , Microbioma Gastrointestinal , Porcinos/metabolismo , Amorphophallus/química , Amorphophallus/metabolismo , Alimentación Animal/análisis , Animales , Bacterias/clasificación , Bacterias/genética , Dieta/veterinaria , Fibras de la Dieta/análisis , Digestión , Ácidos Grasos Volátiles/química , Ácidos Grasos Volátiles/metabolismo , Fermentación , Cinética , Lignina/química , Lignina/metabolismo , Manihot/química , Manihot/metabolismo , Almidón/química , Almidón/metabolismo , Porcinos/microbiología
5.
Water Sci Technol ; 83(9): 2192-2206, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33989186

RESUMEN

Modifying environmentally harmful waste polystyrene foam as an efficient recyclable adsorbent for organic dyes is important. Amidation modified polystyrene (PS-SD) was prepared by the Friedel-Crafts reaction and N,N'-dicyclohexylcarbodiimide (DCC) dehydration condensation reaction of waste polystyrene foam. PS-SD had highly efficient removal performance for organic dyes in large volume water sample solutions, and equilibrium was achieved in 0.5 h. The maximum adsorption capacities for Methylene blue (MB) and Congo red (CR) were 881.62 and 1,880.91 mg/g, respectively, at room temperature according to the Langmuir adsorption isotherm (R2 > 0.99). The kinetic data of the two dyes followed pseudo-second-order kinetics. The removal percentage remained high (>85%) after eight filtration-regeneration cycles. Experimental results showed that PS-SD was an excellent adsorbent for water treatment with high recyclability and long life.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Colorantes , Cinética , Azul de Metileno , Poliestirenos
6.
Ann Anat ; 253: 152210, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38244942

RESUMEN

BACKGROUND: Osseous condition of the mandible was regarded as a key factor influencing stability of implants in the early stage. Finite element analysis was used to assess the effect of bone mass density and alveolar bone resorption (double factors) on stress in a four-unit implant restoration of a free-end edentulous posterior mandible. METHODS: A 3D finite element model was constructed for a single-sided free-end edentulous mandible (from mandibular first premolar to mandibular second molar) containing threaded dental implants. Mandible sensitivity modes were constructed with different alveolar bone resorption levels for normal conditions as well as mild, moderate and severe periodontitis, respectively. Based on the mass density of cancellous bone for four types of bones as the sensitivity parameter, two implant design modes were constructed: Model A (four-unit fixed bridge supported by three implants, implant positions were 34, 36 and 37) and model B: 34 × 36, 37 (37: a single implant crown) (34 × 36: three-unit fixed bridge supported by two implants, implant positions were 34 and 36). A total of 32 sensitivity-based finite element models, grouped in two groups, were constructed. Stress distribution and maximum von Mises stress on cortical bone and cancellous bone around the implant, as well as the surface of implant were investigated by using ABAQUS when vertical loading and 45° oblique loading were applied, respectively. RESULTS: When vertical loading was applied on the implant, maximum von Mises stress on the cortical bone around the implant was assessed to be 4.726 MPa - 13.15 MPa and 6.254 MPa - 13.79 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 2.641 MPa - 3.773 MPa and 2.864 MPa - 4.605 MPa, respectively; maximum stress on the surface of implant was 14.7 MPa - 21.17 MPa and 21.64 MPa - 30.70 MPa, respectively. When 45° oblique loading was applied on the implant restoration, maximum von Mises stress on the cortical bone around the implant was assessed to be 42.08 MPa - 92.71 MPa and 50.84 MPa - 102.5 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 4.88 MPa - 25.95 MPa and 5.227 MPa - 28.43 MPa, respectively; maximum stress on the surface of implant was 77.91 MPa - 124.8 MPa and 109.2 MPa - 150.7 MPa, respectively. Stress peak on the cortical bone and that on cancellous bone around the implant increased and decreased with the decrease in bone mass density, respectively. Stress peak on alveolar bone increased with alveolar bone resorption when oblique loading was applied. CONCLUSION: 1. Both alveolar bone resorption and bone mass density (double factors) are critical to implant restoration. Bone mass density may exhibit a more pronounced impact than alveolar bone resorption. 2. From the biomechanical perspective, types I and II bones are preferred for implant restoration, while implantation should be considered carefully in the case of type III bones, or those with less bone mass density accompanied by moderate to severe alveolar bone loss. 3. Splinting crowns restoration is biomechanically superior to single crown restoration.


Asunto(s)
Pérdida de Hueso Alveolar , Implantes Dentales , Humanos , Pérdida de Hueso Alveolar/cirugía , Análisis de Elementos Finitos , Programas Informáticos , Diente Premolar , Mandíbula/cirugía , Estrés Mecánico , Análisis del Estrés Dental , Prótesis Dental de Soporte Implantado
7.
Shanghai Kou Qiang Yi Xue ; 33(2): 211-218, 2024 Apr.
Artículo en Zh | MEDLINE | ID: mdl-39005102

RESUMEN

PURPOSE: To investigate the effects of different cortical bone thickness and jaw bone density at implant sites on intraoperative pain during implant surgery. METHODS: One hundred and eighty-seven patients(263 implant sites) who underwent implant placement surgery at the Fourth Affiliated Hospital of Nanchang University from August 2021 to August 2022 were selected to investigate the effects of different cortical bone thickness and jaw bone density HU values at implant sites on the anesthetic effect under local infiltration anesthesia with epinephrine in articaine. SPSS 26.0 software package was used for data analysis. RESULTS: The mean cortical bone thickness at the painful sites[(3.90±1.36) mm] was significantly greater than that at the non-painful sites [(2.24±0.66) mm], and the difference was statistically significant(P<0.05). The differences in cortical bone thickness in the mandibular anterior, premolar, and molar regions were statistically significant in the comparison of pain and non-pain sites. The mean HU value of bone density was (764.46±239.75) for the painful sites and (612.23±235.31) for the non-painful sites, with significant difference(P<0.05). The difference was not significant(P>0.05) when comparing the HU values of painful sites with non-painful sites in the mandibular anterior teeth and anterior molar region, while the difference was significant(P<0.05) when comparing the HU values of painful sites with non-painful sites in the mandibular molar region. CONCLUSIONS: Sites with large cortical bone thickness have a greater effect on blocking infiltrative anesthetic penetration and are more prone to intraoperative pain during implantation. In the mandibular anterior and premolar regions, the HU value of the implant sites had less effect on infiltrative anesthetic penetration, and the effect was greater in the mandibular molar region, and the implant sites with high HU values in the mandibular molar region were more likely to have intraoperative pain. When the cortical bone thickness in the planned implant site is greater than 3.9 mm and the mean bone density in the mandibular molar region is greater than 665 HU. If there is sufficient safe distance for hole operation, it is recommended to apply mandibular nerve block anesthesia combined with articaine infiltration anesthesia to avoid intraoperative pain and bad surgical experience for the patients.


Asunto(s)
Densidad Ósea , Hueso Cortical , Mandíbula , Humanos , Densidad Ósea/efectos de los fármacos , Mandíbula/cirugía , Mandíbula/anatomía & histología , Hueso Cortical/anatomía & histología , Implantes Dentales , Anestesia Local/métodos , Dolor/etiología , Carticaína/administración & dosificación
8.
Zootaxa ; 5396(1): 64-73, 2023 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-38220980

RESUMEN

Diplura is a cryptic and edaphic group of hexapod animals characterized by the presence of filiform or pincer-like cerci located at the end of the abdomen. As one of the early diverging lineages of Hexapoda, diplurans play a crucial role in unraveling the origin of the hyperdiverse insects. The fossil record of diplurans, however, is exceptionally limited due to their delicate bodies and habitat requirements. Here we report the discovery of a new japygid, Cretojapyx huangi gen. et sp. nov., entombed in mid-Cretaceous Kachin amber (northern Myanmar). This specimen exhibits distinctive features, including the well-developed carinae on abdominal segment X and cerci, left cercus lacking a prominent tooth and denticles, and right cercus with a postmedian tooth followed by uniseriate round denticles. Our finding provides a unique opportunity to gain valuable insights into the evolutionary history of this ancient lineage and deepen our understanding of terrestrial ecosystems during the Mesozoic.


Asunto(s)
Ámbar , Calcificaciones de la Pulpa Dental , Animales , Ecosistema , Mianmar , Insectos , Fósiles
9.
Ann Anat ; 249: 152111, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37247761

RESUMEN

BACKGROUND: With periodontal disease having an increasing incidence, mandibular free-end edentulism caused by periodontitis is clinically more common. Finite element analysis and clinical case reports were used to evaluate the influence of different designs on the load distribution of implant prosthesis in mandibular posterior free-end edentulism. METHOD: A finite element model of a mandible with posterior free-end edentulism was established. Considering the implant position and selection of single crown repair or splint repair, four designs were conducted including model A: 3435 × 37(four-unit fixed bridge supported by three implants, implant positions were 34, 35, 37); model B: 34,35 × 37, (34: a single implant crown) (35 ×37: three-unit fixed bridge supported by two implants, implant positions were 35, 37); model C: 34 × 3637(four-unit fixed bridge supported by three implants, implant positions were 34, 36, 37); and model D: 34 × 36, 37(37: a single implant crown)(34 ×36: three-unit fixed bridge supported by two implants, implant positions were 34, 36). Stress distribution and the Von Mises stress value of the implants, the crown and the bone around the implants were analyzed at vertical and 45° inclined load. RESULTS: Stress in the cortical bone was mainly concentrated around the implant neck, and maximum Von Mises stress (MVMS) of the four models was 11.6-16.1 MPa at vertical load and 61.74-96.49 MPa at 45° inclined load. Stress in the cancellous bone was concentrated around the implant base, and MVMS of four models was 3.075-3.899 MPa at vertical load and 5.021-6.165 MPa at 45° inclined load. Stress of the restoration crowns was mainly concentrated in the connector of the bridge, and MVMS of four models was 23.38-26.28 MPa at vertical load and 53.14-56.35 MPa at 45° inclined load. Stress of the implant interface was mainly concentrated on the surface of the smaller implants near the bridge, and MVMS of four models was 21.12-33.25 MPa at vertical load and 83.73-138.7 MPa at 45° inclined load. CONCLUSION: There was favorable stress distribution of the four models at vertical load and 45° inclined load. Design of a three-unit fixed bridge combined with a partial crown may be an available option for devising patient treatment plans with mandibular free-end edentulism.


Asunto(s)
Implantes Dentales , Mandíbula , Humanos , Análisis de Elementos Finitos , Estrés Mecánico , Diente Premolar , Mandíbula/cirugía , Dentadura Parcial Fija , Análisis del Estrés Dental , Prótesis Dental de Soporte Implantado , Diseño de Prótesis Dental
10.
J Hazard Mater ; 426: 127799, 2022 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-34802827

RESUMEN

In the study, a novel polymethacryloyl hydrazone modified guar gum adsorption material (GSA) was prepared via condensation between polyhydrazide and dialdehyde guar gum. GSA exhibited an abundant porous structure, higher selectivity for cationic pollutants in high-concentration wastewater like methylene blue (MB), malachite green (MG) dyes, and Cu2+. Under optimized experimental conditions, the maximum equilibrium adsorption capacity of MB, MG, and Cu2+ were 1418.36 mg/g, 1375.58 mg/g, and 196 mg/g, respectively. Adsorption isotherms and kinetics were well fitted with the Langmuir isotherm model and pseudo-second-order kinetic model. The thermodynamic analysis demonstrated that the adsorption process was endothermic, feasible, and spontaneous. Correspondently, the adsorption mechanism was explored by FTIR, SEM-EDS and XPS. The adsorbent was employed in disposing of local sewage water. Additionally, GSA successfully achieves efficient water/oil separation in different salt concentrations with a separation efficiency exceeding 99%.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Colorantes , Galactanos , Hidrazinas , Concentración de Iones de Hidrógeno , Cinética , Mananos , Azul de Metileno , Gomas de Plantas , Polimetil Metacrilato
11.
Phytomedicine ; 102: 154163, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35597027

RESUMEN

BACKGROUND: Artemisia anomala S. Moore (Compositae), known as "Nan-Liu-Ji-Nu" in traditional Chinese medicine (TCM), has been used to treat many inflammatory diseases, including enteritis, acute icteric hepatitis, rheumatism, toothache, tonsillitis, and chronic bronchitis, for centuries. Our preliminary studies have demonstrated that the ethanolic extract of A. anomala (EAA) might be with the potential of inhibiting the activation of the NLRP3 inflammasome. However, the anti-inflammatory activity of EAA based on NLRP3 inflammasome inhibition is still unclear. PURPOSE: This work aimed to elucidate the anti-inflammatory mechanism of EAA by inhibiting NLRP3 inflammasome activation. METHODS: Lipopolysaccharide (LPS)-primed bone marrow-derived macrophages (BMDMs) were used to evaluate the inhibitory effects on NLRP3 inflammasome activation. The level of IL-1ß was determined by ELISA. The expression levels of IL-1ß, caspase-1, NLRP3, and ASC were assayed using western blot analysis. ASC oligomerization and speck formation were detected by immunofluorescence microscopy. The measurements of intracellular chloride and potassium were conducted using N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) probe assay and inductively coupled plasma-optical emission spectrometry (ICP-OES), respectively. Mitochondrial reactive oxygen species (mtROS) were examined using the MitoSOX method. Acridine orange (AO) staining was used to detect the permeability of the lysosomal membrane. A DSS-induced ulcerative colitis model was established to evaluate the anti-inflammatory effects of EAA in vivo. Finally, high-performance liquid chromatography (HPLC) was employed to identify and quantify the major constituents of EAA. RESULTS: In BMDMs, EAA significantly inhibited the release of IL-1ß induced by LPS. The mechanistic study revealed that EAA inhibited NLRP3 inflammasome activation by blocking the oligomerization of ASC and suppressed the LPS-induced priming step. Furthermore, EAA protected lysosomes by inhibiting the TAK1-JNK pathway, thereby inhibiting the assembly of downstream NLRP3 inflammasome and the production of IL-1ß. In addition, EAA exerted potent protective effects in an ulcerative colitis model by decreasing the content of colonic IL-1ß and alleviating the process of ulcerative colitis. HPLC analysis identified eight main components of EAA, including isofraxidin (1), quercetin-7-O-ß-D-glucopyranoside (2), apigenin-7-O-ß-D-glucopyranoside (3), 7-methoxycoumarin (4), quercetin (5), luteolin (6), kaempferol (7), and eupatorin (8), Of these compounds, quercetin and kaempferol were found to be the most potent ingredients. CONCLUSION: These findings collectively reveal that EAA exerts anti-inflammatory effects by both suppressing the NLRP3 priming step and protecting lysosomes to inhibit NLRP3 inflammasome activation, suggesting that this traditional herbal medicine might be used to treat NLRP3-driven inflammatory diseases.


Asunto(s)
Artemisia , Colitis Ulcerosa , Antiinflamatorios/farmacología , Caspasa 1/metabolismo , Inflamasomas , Interleucina-1beta/metabolismo , Quempferoles , Lipopolisacáridos/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Extractos Vegetales/farmacología , Quercetina
12.
ACS Appl Mater Interfaces ; 14(2): 2564-2577, 2022 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-34981928

RESUMEN

Supramolecular chemistry provides huge potentials and opportunities in agricultural pest management. In an attempt to develop highly bioactive, eco-friendly, and biocompatible supramolecular complexes for managing intractable plant bacterial diseases, herein, a type of interesting adamantane-functionalized 1,3,4-oxadiazole was rationally prepared to facilitate the formation of supramolecular complexes via ß-cyclodextrin-adamantane host-guest interactions. Initial antibacterial screening revealed that most of these adamantane-decorated 1,3,4-oxadiazoles were obviously bioactive against three typically destructive phytopathogens. The lowest EC50 values could reach 0.936 (III18), 0.889 (III18), and 2.10 (III19) µg/mL against the corresponding Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). Next, the representative supramolecular binary complex III18@ß-CD (binding mode 1:1) was successfully fabricated and characterized by 1H nuclear magnetic resonance (NMR), isothermal titration calorimetry (ITC), high-resolution mass spectrometry (HRMS), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Eventually, correlative water solubility and foliar surface wettability were significantly improved after the formation of host-guest assemblies. In vivo antibacterial evaluation found that the achieved supramolecular complex could distinctly alleviate the disease symptoms and promote the control efficiencies against rice bacterial blight (from 34.6-35.7% (III18) to 40.3-43.6% (III18@ß-CD)) and kiwi canker diseases (from 41.0-42.3% (III18) to 53.9-68.0% (III18@ß-CD)) at 200 µg/mL (active ingredient). The current study can provide a feasible platform and insight for constructing biocompatible supramolecular assemblies for managing destructive bacterial infections in agriculture.


Asunto(s)
Adamantano/farmacología , Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Materiales Biocompatibles/farmacología , Oxadiazoles/farmacología , beta-Ciclodextrinas/farmacología , Adamantano/química , Antibacterianos/síntesis química , Antibacterianos/química , Materiales Biocompatibles/síntesis química , Materiales Biocompatibles/química , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oryza/microbiología , Oxadiazoles/química , Pseudomonas/efectos de los fármacos , Xanthomonas/efectos de los fármacos , beta-Ciclodextrinas/química
13.
Acta Biomater ; 154: 412-423, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36280028

RESUMEN

Nanoparticle-anchored platelet systems hold great potential to act as drug carriers in post-surgical cancer treatment due to their intrinsic ability to target the bleeding sites. However, rational design is still needed to further improve its cargo release profiles to meet the cytosolic delivery of therapeutic proteins with intracellular targets. Herein, we developed a tumor microenvironment (TME)-responsive backpack-conjugated platelet system to enhance intracellular protein delivery, thereby significantly inhibiting tumor recurrence after surgery. Specifically, protein nanogels encapsulating GALA and Granzyme B (GrB) are conjugated on the platelet surface via an acid-sensitive benzoic-imine linker through a biorthogonal reaction (GALA-GNGs-P). Taking advantage of wound-tropism of platelets, GALA-GNGs-P could actively accumulate at the surgical trauma and release nanogels in response to acidic TME for promoting deep penetration. Following cellular uptake, the pore-forming peptide GALA helps nanogels escape from lysosome. Subsequently, high glutathione (GSH) concentration in tumor cytoplasm facilitates GrB release from NGs, leading to intense cell apoptosis. GALA-GNGs-P shows remarkable tumor-targeting capability, high cellular uptake, and outstanding lysosomal escaping ability, which can significantly inhibit tumor recurrence in mice models with incomplete tumor resection. Our findings indicate that platelets bioengineered with TME-responsive protein nanogels provide an option to intracellularly deliver therapeutic proteins for the post-surgical treatment of cancer. STATEMENT OF SIGNIFICANCE: Platelet-based drug delivery systems (DDSs) have gained considerable achievements in post-surgical cancer treatment. However, there is no research exploring their potential in realizing the controllable release of cargoes in the acidic tumor microenvironment (TME). Herein, we developed a TME-responsive bioengineered platelet delivery platform (GALA-GNGs-P) for achieving controllable and effective protein intracellular delivery to overcome post-surgical tumor recurrence. Our surface-anchored nanogel-platelet system has the following advantages: (i) improving the loading efficiency of therapeutic proteins, (ii) affecting no physiological function of platelets, (iii) realizing on-demand cargo release in the acidic TME, and (iv) helping proteins escape from endosomal entrapment. Our findings further explored the prospect of cellular backpack system and realized the controllable release of cargoes in the acidic TME.


Asunto(s)
Neoplasias , Microambiente Tumoral , Ratones , Animales , Proteínas de la Membrana , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nanogeles , Sistemas de Liberación de Medicamentos , Neoplasias/tratamiento farmacológico
14.
Int J Pharm ; 578: 119075, 2020 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-31991187

RESUMEN

Hydrogels formed through reversible supramolecular interactions may attain self-healing in the in situ environment. However, the low grafting degree of functional groups and steric hindrance effect of polymer backbones significantly reduced the self-healing efficacy and kinetics. To overcome these deficiencies, we designed a novel hydrogel via non-covalent host-guest interaction between ß-cyclodextrin modified hyaluronic acid (HA-CD) and adamantane modified 4-arm-PEG (4-arm-PEG-Ad). The multi-armed monomer enabled to increase the number of functional groups and avoid steric hindrance effects, offering more efficient host-guest interaction. The insoluble dexamethasone could be loaded in the ß-CDs' hydrophobic cavities. The designed hydrogels exhibited excellent self-healing properties. The mechanical strengths, swelling rate and release of dexamethasone could be adjusted by adding 4-arm-PEG-Ad. The novel hydrogels significantly improved the therapeutic effect of the dexamethasone in burn wound healing. Herein, these hydrogels had great potential for direct, convenient, and efficient delivery of hydrophobic drugs and improved their therapeutic effects.


Asunto(s)
Adamantano , Sistemas de Liberación de Medicamentos , Ácido Hialurónico , Hidrogeles , Polietilenglicoles , beta-Ciclodextrinas , Células 3T3 , Adamantano/administración & dosificación , Adamantano/química , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/química , Quemaduras/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados/administración & dosificación , Reactivos de Enlaces Cruzados/química , Dexametasona/administración & dosificación , Dexametasona/química , Liberación de Fármacos , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/química , Hidrogeles/administración & dosificación , Hidrogeles/química , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Ratas Sprague-Dawley , Cicatrización de Heridas/efectos de los fármacos , beta-Ciclodextrinas/administración & dosificación , beta-Ciclodextrinas/química
15.
ACS Nano ; 13(6): 7010-7023, 2019 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-31188559

RESUMEN

Photodynamic therapy (PDT) shows a promising synergy with chemotherapy in the therapeutic outcome of malignant cancers. The minimal invasiveness and nonsystemic toxicity are appealing advantages of PDT, but combination with chemotherapy brings in the nonselective toxicity. We designed a polymeric nanoparticle system that contains both a chemotherapeutic agent and a photosensitizer to seek improvement for chemo-photodynamic therapy. First, to address the challenge of efficient co-delivery, polymer-conjugated doxorubicin (PEG-PBC-TKDOX) was synthesized to load photosensitizer chlorin e6 (Ce6). Ce6 is retained with DOX by a π-π stacking interaction, with high loading (41.9 wt %) and the optimal nanoparticle size (50 nm). Second, light given in PDT treatment not only excites Ce6 to produce cytotoxic reactive oxygen species (ROS) but also spatiotemporally activates a cascade reaction to release the loaded drugs. Finally, we report a self-destructive polymeric carrier (PEG-PBC-TKDOX) that depolymerizes its backbone to facilitate drug release upon ROS stimulus. This is achieved by grafting the ROS-sensitive pendant thioketal to aliphatic polycarbonate. When DOX is covalently modified to this polymer via thioketal, target specificity is controlled by light, and off-target delivery toxicity is mostly avoided. An oral squamous cell carcinoma that is clinically relevant to PDT was used as the cancer model. We put forward a polymeric system with improved efficiency for chemo-photodynamic therapy and reduced off-target toxicity.


Asunto(s)
Liberación de Fármacos , Neoplasias Experimentales/tratamiento farmacológico , Fotoquimioterapia/métodos , Polímeros de Estímulo Receptivo/síntesis química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Femenino , Humanos , Células MCF-7 , Masculino , Ratones , Ratones Desnudos , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Polímeros de Estímulo Receptivo/farmacocinética
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