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In this study, the enantioselectivity of ß-cyclodextrin and its derivatives towards propranolol enantiomers are investigated by molecular dynamic (MD) simulations. ß-cyclodextrin (ß-CD) have previously been shown to be able to recognize propranolol (PRP) enantiomers. To improve upon the enantioselectivity of ß-cyclodextrin, we propose the use of an ionic-liquid-modified-ß-cyclodextrin (ß-CD-IL). ß-CD-IL was found to be able to complex R and S propranolol enantiomers with differing binding energies. The molecular docking study reveals that the ionic liquid chain attached to the ß-CD molecule has significant interaction with propranolol. The formation of the most stable complex occurred between (S)-ß-CD-IL and (S)-propranolol with an energy of -5.80 kcal/mol. This is attributed to the formation of a hydrogen bond between the oxygen of the propranolol and the hydrogen on the primary rim of the (S)-ß-CD-IL cavity. This interaction is not detected in other complexes. The root mean-squared fluctuation (RMSF) value indicates that the NH group is the most flexible molecular fragment, followed by the aromatic group. Also of note, the formation of a complex between pristine ß-CD and (S)-propranolol is the least favorable.
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The regioselective radical CH trifluoromethylation of aromatic compounds have been shown to proceed in good yield and high regioselectivity when cyclodextrin (CD) is present. Yet, the reaction mechanism and the role of CD during the reaction have remained obscure. To this end, here we performed density functional theory (DFT) calculations to the conformations obtained by semiempirical quantum mechanical molecular dynamics calculations to reveal the reaction mechanism and the role of CD in controlling regioselectivity. The results show that metal salt increases the yield but do not affect the regioselectivity, which we further confirmed by an experiment. In contrast, multiple CD-substrate complex conformations and reaction pathways were obtained, and CD was shown to contribute to improving the regioselectivity by stabilizing the intermediate state via encapsulation. The present study indicates that CDs can increase the regioselectivity by stabilizing the intermediate and product states while only marginally affecting the transition state.
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BACKGROUND: Generating targeted mutant mice is a crucial technology in biomedical research. This study focuses on optimizing the CRISPR/Cas9 system uptake into sperm cells using the methyl ß-cyclodextrin-sperm-mediated gene transfer (MBCD-SMGT) technique to generate targeted mutant blastocysts and mice efficiently. Additionally, the present study elucidates the roles of cholesterol and reactive oxygen species (ROS) in the exogenous DNA uptake by sperm. RESULTS: In this study, B6D2F1 mouse sperm were incubated in the c-TYH medium with different concentrations of MBCD (0, 0.75, 1, and 2 mM) in the presence of 20 ng/µl pCAG-eCas9-GFP-U6-gRNA (pgRNA-Cas9) for 30 min. Functional parameters, extracellular ROS, and the copy numbers of internalized plasmid per sperm cell were evaluated. Subsequently, in vitro fertilization (IVF) was performed and fertilization rate, early embryonic development, and transfection rate were assessed. Finally, our study investigated the potential of the MBCD-SMGT technique in combination with the CRISPR-Cas9 system, referred to as MBCD-SMGE (MBCD-sperm-mediated gene editing), for generating targeted mutant blastocysts and mice. Results indicated that cholesterol removal from the sperm membrane using MBCD resulted in a premature acrosomal reaction, an increase in extracellular ROS levels, and a dose-dependent influence on the copy numbers of the internalized plasmids per sperm cell. Moreover, the MBCD-SMGT technique led to a larger population of transfected motile sperm and a higher production rate of GFP-positive blastocysts. Additionally, the current study validated the targeted indel in blastocyst and mouse derived from MBCD-SMGE technique. CONCLUSION: Overall, this study highlights the significant potential of the MBCD-SMGE technique for generating targeted mutant mice. It holds enormous promise for modeling human diseases and improving desirable traits in animals.
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Transparent materials are widely used in industries, everyday life, and scientific activities. The development of new, lightweight, and durable artificial transparent materials is a challenge in synthetic chemistry. In this study, a supramolecular approach is conceived to construct transparent glass. Cyclodextrins are selected as the building blocks for the fabrication of supramolecular glass via noncovalent polymerization. The newly formed glass displays several attractive advantages, including good thermal processability, high mechanical strength and dielectric constant, excellent visible light transparency, and good adhesion performance. Importantly, the structural characteristics of long-range disorder and short-range order are observed in cyclodextrin glass. Here a new strategy is presented for the preparation and functionalization of low-molecular-weight transparent materials.
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Thermoresponsive nanogels (tNGs) are promising candidates for dermal drug delivery. However, poor incorporation of hydrophobic drugs into hydrophilic tNGs limits the therapeutic efficiency. To address this challenge, ß-cyclodextrins (ß-CD) are functionalized by hyperbranched polyglycerol serving as crosslinkers (hPG-ßCD) to fabricate ßCD-tNGs. This novel construct exhibits augmented encapsulation of hydrophobic drugs, shows the appropriate thermal response to dermal administration, and enhances the dermal penetration of payloads. The structural influences on the encapsulation capacity of ßCD-tNGs for hydrophobic drugs are analyzed, while concurrently retaining their efficacy as skin penetration enhancers. Various synthetic parameters are considered, encompassing the acrylation degree and molecular weight of hPG-ßCD, as well as the monomer composition of ßCD-tNGs. The outcome reveals that ßCD-tNGs substantially enhance the aqueous solubility of Nile Red elevating to 120 µg mL-1 and augmenting its dermal penetration up to 3.33 µg cm-2. Notably, the acrylation degree of hPG-ßCD plays a significant role in dermal drug penetration, primarily attributed to the impact on the rigidity and hydrophilicity of ßCD-tNGs. Taken together, the introduction of the functionalized ß-CD as the crosslinker in tNGs presents a novel avenue to enhance the efficacy of hydrophobic drugs in dermatological applications, thereby offering promising opportunities for boosted therapeutic outcomes.
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Glicerol , Interações Hidrofóbicas e Hidrofílicas , Nanogéis , Polímeros , beta-Ciclodextrinas , beta-Ciclodextrinas/química , Glicerol/química , Nanogéis/química , Polímeros/química , Animais , Polietilenoimina/química , Reagentes de Ligações Cruzadas/química , Temperatura , Absorção Cutânea , Pele/metabolismo , Polietilenoglicóis/química , OxazinasRESUMO
In this work, multi-layer Ti3C2 - carbon nanotubes - gold nanoparticles (Ti3C2-CNTs-Au) and cyclodextrin metal-organic framework - carbon nanotubes (CD-MOF-CNTs) have been prepared by in situ growth method and used to construct the ultra-sensitive rutin electrochemical sensor for the first time. Among them, the large number of metal active sites of Ti3C2, the high electron transfer efficiency of CNTS, and the good catalytic properties of AuNPs significantly enhance the electrochemical properties of the composite carbon nanomaterials. Interestingly, CD-MOF has a unique host-guest recognition and a large number of cavities, molecular gaps, and surface reactive groups, which gives the composite outstanding accumulation properties and selectivity for rutin. Under the optimized conditions, the constructed novel sensor has satisfactory detection performance for rutin in the range of 2 × 10-9 to 8 × 10-7 M with a limit of detection of 6.5 × 10-10 M. In addition, the sensor exhibits amazing anti-interference performance against rutin in some flavonoid compounds and can be used to test natural plant samples (buckwheat, Cymbopogon distans, and flos sophorae immaturus). This work has promising applications in the field of environmental and food analysis, and exploring new directions for the application of Mxene-based composites.
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Ciclodextrinas , Ouro , Nanotubos de Carbono , Rutina , Titânio , Rutina/química , Rutina/análise , Ouro/química , Ciclodextrinas/química , Nanotubos de Carbono/química , Titânio/química , Estruturas Metalorgânicas/química , Nanopartículas Metálicas/química , Técnicas Eletroquímicas/métodosRESUMO
To address the issue of bacterial growth on fresh-cut fruits, this paper reports the synthesis of nanosized γ-cyclodextrin metal-organic frameworks (CD-MOFs) using an ultrasound-assisted method and their application as carriers of limonene for antibacterial active packaging. The effects of the processing parameters on the morphology and crystallinity of the CD-MOFs are investigated, and the results prove that the addition of methanol is the key to producing nanosized CD-MOFs. The limonene loading content of the nanosized CD-MOFs can reach approximately 170 mg g-1. The sustained-release behaviors of limonene in the CD-MOFs are evaluated. Molecular docking simulations reveal the distribution and binding sites of limonene in the CD-MOFs. CD-MOFs are deposited on the surfaces of polycaprolactone (PCL) nanofibers via an immersion method, and limonene-loaded CD-MOF@PCL nanofibers are prepared. The morphology, crystallinity, thermal stability, mechanical properties, and antibacterial activity of the nanofibers are also studied. The nanofiber film effectively inhibits bacterial growth and prolongs the shelf life of fresh-cut apples. This study provides a novel strategy for developing antibacterial active packaging materials based on CD-MOFs and PCL nanofibers.
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Frutas , Limoneno , Estruturas Metalorgânicas , Nanofibras , Poliésteres , gama-Ciclodextrinas , Limoneno/química , Limoneno/farmacologia , Nanofibras/química , Poliésteres/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , gama-Ciclodextrinas/química , Frutas/química , Terpenos/química , Terpenos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Simulação de Acoplamento MolecularRESUMO
The influence of alpha-cyclodextrin (αCD) on PEG crystallization is examined for a peptide-PEG conjugate, YYKLVFF-PEG3k comprising an amyloid peptide YYKLVFF linked to PEG with molar mass 3â kg mol-1. Remarkably, differential scanning calorimetry (DSC) and simultaneous synchrotron small-angle/wide-angle X-ray scattering (SAXS/WAXS) show that crystallization of PEG is suppressed by αCD, provided that the cyclodextrin content is sufficient. A hexagonal mesophase is formed instead. The αCD threading reduces the conformational flexibility of PEG, and hence suppresses crystallization. These results show that addition of cyclodextrins can be used to tune the crystallization of peptide-polymer conjugates and potentially other polymer/biomolecular hybrids.
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Cristalização , Peptídeos , Polietilenoglicóis , Polietilenoglicóis/química , Peptídeos/química , Varredura Diferencial de Calorimetria , Ciclodextrinas/química , Difração de Raios X , alfa-Ciclodextrinas/química , Espalhamento a Baixo ÂnguloRESUMO
The activity of neuronal Kv7.2/Kv7.3 channels is critically dependent on PIP2 and finely modulated by cholesterol. Here, we report the crosstalk between cholesterol and PIP2 in the regulation of Kv7.2/Kv7.3 channels. Our results show that currents passing through Kv7.2/Kv7.3 channels in cholesterol-depleted cells, by acute application of methyl-ß-cyclodextrin (MßCD), were less sensitive to PIP2 dephosphorylation strategies than those of control cells, suggesting that cholesterol depletion enhances the Kv7.2/Kv7.3-PIP2 interaction. In contrast, the sensitivity of Kv7.2/Kv7.3 channels to acute membrane cholesterol depletion by MßCD was not altered in mutant channels with different apparent affinities for PIP2.
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ColesterolRESUMO
This research focuses on the development and validation of a capillary electrophoresis (CE) method for the chiral separation of three H1-antihistamine drugs chlorcyclizine, norchlorcyclizine, and neobenodine using sulfated ß-cyclodextrin (S-ß-CD) as the chiral selector. The study explores various factors influencing the separation efficiency, including CD concentration, organic modifier content, voltage application, and buffer pH. Optimal conditions were identified as a 100 mM phosphate buffer (pH 6.0) with 34 mg mL-1 S-ß-CD and 40% (v/v) methanol. The method demonstrated excellent linearity in calibration curves, with coefficients of determination exceeding 0.99 for each enantiomer. Precision studies revealed good intra- and inter-day precision for migration times and peak areas. The limits of detection and quantification for the analytes were within the ranges of 5.9-11.4 and 18-34.6 µmol L-1, respectively. Overall, the developed CE method offers a robust and precise approach for the chiral separation of H1-antihistamine drugs, holding promise for pharmaceutical applications.
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Eletroforese Capilar , Limite de Detecção , beta-Ciclodextrinas , Eletroforese Capilar/métodos , beta-Ciclodextrinas/química , Estereoisomerismo , Reprodutibilidade dos Testes , Piperazinas/química , Piperazinas/análise , Modelos Lineares , Concentração de Íons de Hidrogênio , Sulfatos/química , Sulfatos/análiseRESUMO
In recent decades, many efforts have been devoted to studying reactions catalyzed in nanoconfined spaces. The most impressive aspect of catalysis in nanoconfined spaces is that the reactivity of the molecules can be smartly driven to disobey classical behavior. A green and efficient three-component aza-Darzens (TCAD) reaction using a catalytic amount of γ-cyclodextrins (CDs) in water has been developed to synthesize N-phenylaziridines. CDs effectively performed this reaction in an environmentally friendly setting, achieving good yields. The same reaction was then performed using polymeric γ-CD such as a γ-cyclodextrin polymer crosslinked (GCDPC) with epichlorohydrin, a sponge-like macroporous γ-cyclodextrin-based cryogel (GCDC), and a γ-cyclodextrin-based hydrogel (GCDH). The homogeneous and heterogeneous catalyst recovery was then studied, and it was proved to be easily recycled several times without relevant activity loss. Water, as a unique and eco-friendly reaction medium, has been utilized for the first time, to the best of our knowledge, in this reaction. The inclusion of the reagents in CDs has been studied and rationalized by NMR spectroscopy experiments and molecular modeling calculations. The credit of the presented protocol includes good yields and catalyst reusability and precludes the use of organic solvents.
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Slightly different reaction conditions afforded two distinct cavity-shaped cis-chelating diphosphanes from the same starting materials, namely diphenyl(2-phosphanylphenyl)phosphane and an α-cyclodextrin-derived dimesylate. Thanks to their metal-confining properties, the two diphosphanes form only mononuclear [CuX(PP)] complexes (X=Cl, Br, or I) with the tricoordinated metal ion located just above the center of the cavity. The two series of CuI complexes display markedly different luminescence properties that are both influenced by the electronic properties of the ligand and the unique steric environment provided by the cyclodextrin (CD) cavity. The excited state lifetimes of all complexes are significantly longer than those of the cavity-free analogues suggesting peculiar electronic effects that affect radiative deactivation constants. The overall picture stemming from absorption and emission data suggests close-lying charge-transfer (MLCT, XLCT) and triplet ligand-centered (LC) excited states.
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The application of flavoring ingredients like menthol in the food industry is hindered by their high volatility and poor thermal stability, which lead to significant losses during processing and storage. Encapsulation of flavors into porous materials to obtain inclusion complexes (ICs) has proved to be an efficient strategy. In the present study, we synthesized a series of relatively food-safe three-dimensional anionic cyclodextrin-based covalent organic frameworks (CD-COFs) with spiroborate linkages using a facile microwave-assisted method. The high surface area and newly formed cavities of COFs significantly enhanced the encapsulation efficiency of menthol compared to native CD materials. Our findings revealed that γ-CD-COF-Li, with Li+ as the counterion, achieved superior encapsulation efficiency of 25.9 %, outperforming γ-CD-COF-Na, γ-CD-COF-K and α-CD-COF-Li under the same conditions. Thermal stability measurements show that the menthol/γ-CD-COF-Li-ICs effectively stabilize menthol against heat evaporation at elevated temperatures due to the strengthened interaction between menthol and γ-CD-COF-Li. The promising results of this research suggest that rapid advancements in COF technology will provide new opportunities for enhancing the stability of flavoring ingredients in the food industry.
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Photosynthesis is a complex multi-step process in which light collection is the initial step of photosynthesis and plays an important role in the utilization of solar energy. In order to improve the utilization of sunlight, researchers have developed a variety of artificial light-harvesting systems to simulate photosynthesis in nature. Here, we report a supramolecular artificial light-harvesting system in aqueous solution. Since ß-cyclodextrin (ß-CD) has a hydrophobic cavity and a hydrophilic outer surface, we adopt ß-cyclodextrin (ß-CD) as the host molecule and use adamantane as the guest molecule. At the same time, we modified ß-CD with the donor molecule naphthalimide and adamantane with the tetraphenylethylene molecule which has aggregation-induced emission (AIE) effects. By using fluorescent molecules with AIE, the self-quenching effect caused by aggregation in aqueous solution can be effectively avoided. Due to the host-guest interaction of ß-CD and adamantane, nanoparticles with stable structure and uniform size can be spontaneously assembled in water. Because of the close distance and strong spectral overlap between naphthalimide and tetraphenylethylene, Förster resonance energy transfer (FRET) was realized, and artificial light-harvesting system was successfully constructed in aqueous solution. Therefore, this study provides a new strategy for constructing artificial light-harvesting system, and the artificial light-harvesting system shows broad application prospects in aqueous solutions.
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Amphiphilic supramolecular materials based on biodegradable cyclodextrins (CDs) have been known to self-assemble into different types of thermotropic liquid crystals, including smectic and hexagonal columnar mesophases. Previous studies on amphiphilic CDs bearing 14 aliphatic chains at the primary face and 7 oligoethylene glycol (OEG) chains at the secondary face showed that the stability of the mesophase can be rationally tuned through implemation of terminal functional groups to the OEG chains. Here, we report the syntheses of first examples of crown ether-functionalized amphiphilic cyclodextrins that unexpectedly form thermotropic bicontinuous cubic phases. This constitutes the first reported examples of cyclodextrins forming such phases, which are potentially capable of 3D ion transport. Lithium composites were made to assess lithium conduction in the material. XRD revealed the added lithium salt destabilizes the cubic phase in favour of the smectic phase. Solid-state NMR studies showed that these materials conduct lithium ions with a very low activation energy.
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Nanocone clusters (NCCs) have been developed as clusters with inclusion complexes of FDA-approved ß-cyclodextrin (ßCD) and perfluorocarbons (PFC) (i.e., perfluoropentane (PFP) and perfluorohexane (PFH)) and have shown promise in nanoparticle-mediated histotripsy (NMH) applications owing to their lowered cavitation threshold, ease of production, and fluorocarbon quantification. However, there is still a lack of information on the best conditions of the synthesis of NCCs as a product that can have a maximum determinable fluorocarbon content and maintain the stability of the NCC during synthesis and when used as histotripsy agents or exposed to physiological conditions. These concerns about the stability of the clusters and the best possible formulation are investigated in the current work. The cluster formation potential was tested taking into consideration the nature of both PFCs and ßCD by employing different synthesis conditions in terms of solution and environmental parameters such as concentration of solvent, stoichiometry between ßCD and PFCs, temperature, pH, solvent type, etc. The best route of synthesis was then translated into various batch sizes and investigated in terms of the PFC loading and yield. These studies revealed that preparing NCCs in double-distilled water in an ice bath at the optimized solution concentration gave the highest yields and optimal PFC loading, as determined from gas chromatography. Furthermore, the stability of the clusters with different stoichiometries was scrutinized in varying concentrations, mechanical disruption times, pH levels, and temperature conditions, showing effects on each cluster's particle size in dynamic light scattering, visualized in transmission electron microscopy, and cavitation behavior in agarose gel tissue phantoms. These studies revealed stable clusters for all formulations, with PFH-containing NCCs emerging to be the most stable in terms of their cluster size and bubble formation potential in histotripsy. Finally, the shelf life of these clusters was investigated using DLS, which revealed a stable cluster. In conclusion, NCCs have shown high stability in terms of both synthesis, which can be replicated in gram-level production, and the cluster itself, which can be exposed to harsher conditions and still form stable bubbles in histotripsy.
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Fluorocarbonos , Nanopartículas , beta-Ciclodextrinas , Fluorocarbonos/química , beta-Ciclodextrinas/química , Nanopartículas/química , Solventes/química , Temperatura , Concentração de Íons de Hidrogênio , PentanosRESUMO
Folate uptake is largely mediated by folate receptor (FR)ß, encoded by FOLR2 gene, in myeloid immune cells such as granulocytes, monocytes, and especially in macrophages that constitute the reticuloendothelial system (RES) and infiltrate the tumor microenvironment. Since the myeloid immune compartment dynamically changes during tumorigenesis, it is critical to assess the infiltration status of the tumors by FRß-expressing myeloid cells to better define the targeting efficacy of folate-functionalized drug delivery systems. On the other hand, clearance by RES is a major limitation for the targeting efficacy of nanoparticles decorated with folate. Therefore, the aims of this study are (i) to determine the amount and subtypes of FRß+ myeloid cells infiltrating the tumors at different stages, (ii) to compare the amount and subtype of FRß+ myeloid cells in distinct organs of tumor-bearing and healthy animals, (iii) to test if the cancer-targeting efficacy and biodistribution of a prototypic folate-functionalized nanoparticle associates with the density of FRß+ myeloid cells. Here, we report that myeloid cell infiltration was enhanced and FRß was upregulated at distinct stages of tumorigenesis in a mouse breast cancer model. The CD206+ subset of macrophages highly expressed FRß, prominently both in tumor-bearing and healthy mice. In tumor-bearing mice, the amount of all myeloid cells, but particularly granulocytes, was remarkably increased in the tumor, liver, lungs, spleen, kidneys, lymph nodes, peritoneal cavity, bone marrow, heart, and brain. Compared with macrophages, the level of FRß was moderate in granulocytes and monocytes. The density of FRß+ immune cells in the tumor microenvironment was not directly associated with the tumor-targeting efficacy of the folate-functionalized cyclodextrin nanoparticles. The lung was determined as a preferential site of accumulation for folate-functionalized nanoparticles, wherein FRß+CD206+ macrophages significantly engulfed cyclodextrin nanoparticles. In conclusion, our results demonstrate that the tumor formation augments the FR levels and alters the infiltration and distribution of myeloid immune cells in all organs which should be considered as a major factor influencing the targeting efficacy of nanoparticles for drug delivery.
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Receptor 2 de Folato , Ácido Fólico , Sistema Fagocitário Mononuclear , Células Mieloides , Nanopartículas , Microambiente Tumoral , Animais , Ácido Fólico/química , Ácido Fólico/farmacocinética , Receptor 2 de Folato/metabolismo , Camundongos , Nanopartículas/química , Células Mieloides/metabolismo , Células Mieloides/efeitos dos fármacos , Distribuição Tecidual , Feminino , Sistema Fagocitário Mononuclear/metabolismo , Humanos , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Camundongos Endogâmicos BALB CRESUMO
Melanoma is an aggressive skin cancer notorious for high levels of drug resistance. Additionally, current treatments such as immunotherapies are often associated with numerous adverse side effects. The use of nitric oxide (NO) may represent an attractive treatment for melanoma due to NO's various anticancer properties, unlikeliness to foster resistance, and limited toxicity toward healthy tissues. The anticancer effects of chemical NO donors have been explored previously but with limited understanding of the needed characteristics for exerting optimal antimelanoma activity. Herein, the in vitro therapeutic efficacy of three macromolecular NO donor systems (i.e., cyclodextrin, mesoporous silica nanoparticles, and hyaluronic acid) with tunable NO-release kinetics was explored by evaluating skin permeation along with toxicity against melanoma and healthy skin cells. Cytotoxicity against melanoma cells was dependent on NO payload and not donor identity or NO-release kinetics. In contrast, cytotoxicity against healthy cells was primarily influenced by the macromolecular NO donor, with cyclodextrin- and hyaluronic acid-based NO donors having the highest therapeutic indices. In vitro skin permeation was influenced by both the size and charge of the NO donor, with smaller, more neutral donors resulting in greater permeation. A Pluronic F127 organogel was optimized for the delivery of a cyclodextrin-based NO donor. Delivery of the NO donor in this manner resulted in increased in vitro skin permeation and reduced tumor growth in an in vivo model.
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Ácido Hialurônico , Melanoma , Nanopartículas , Doadores de Óxido Nítrico , Óxido Nítrico , Neoplasias Cutâneas , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Animais , Óxido Nítrico/metabolismo , Ácido Hialurônico/química , Melanoma/tratamento farmacológico , Melanoma/patologia , Humanos , Camundongos , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia , Nanopartículas/química , Linhagem Celular Tumoral , Ciclodextrinas/química , Administração Cutânea , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Dióxido de Silício/química , Poloxâmero/química , Administração Tópica , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Feminino , Melanoma Maligno CutâneoRESUMO
Improving nanomedicine uptake by tumor cells is key to achieving intracellular drug delivery. In this study, we found that methyl-ß-cyclodextrin (MßCD) can significantly promote the intracellular accumulation of nanoparticulated α-linolenic acid-paclitaxel conjugates (ALA-PTX NPs) via enhanced clathrin-mediated endocytosis and limited degradation in lysosomes. Our in vitro results indicated that MßCD not only reduced the plasma membrane cholesterol content and increased plasma membrane fluidity, leading to ALA-PTX NPs being more easily incorporated into the plasma membrane, further enhancing membrane fluidity and making the plasma membrane more susceptible to tensile deformation, forming intracellular vesicles to enhance ALA-PTX NP cellular uptake, but also destroyed lysosomes and then limited ALA-PTX NPs' degradation in lysosomes. In HepG2 tumor-bearing mice, MßCD was also able to enhance the antitumor activity of ALA-PTX NPs in vivo. Moreover, we found that MßCD specifically promoted PUFA-paclitaxel conjugate NP cellular uptake. The cellular uptake of PTX liposome which shares an endocytosis pathway with ALA-PTX NPs could be enhanced by MßCD combined with ALA or ALA-PTX NPs. Therefore, we suggested that MßCD combined with polyunsaturated fatty acid-conjugation would be an effective strategy for improving intracellular delivery of nanoparticulated chemotherapeutic drugs used for combination administration to enhance antitumor efficiency.
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Quercetin is a natural flavonoid with antioxidant, anti-inflammatory, and antibacterial properties. This work aimed to formulate quercetin-cyclodextrin microcapsules (QT-ß-CD) while examining their photodynamic antibacterial effects and underlying mechanisms in detail. Characterization of the QT-ß-CD was conducted using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The bacteriostatic effects of UV-A irradiation on Escherichia coli O157:H7 (E. coli O157:H7) were investigated. The photodynamic impact of QT-ß-CD was assessed by analyzing hydrogen peroxide (H2O2) production. The antimicrobial activity was further elucidated through examinations of cell membrane integrity, protein damage, changes in cellular motility, biofilm formation, and extracellular polysaccharide reduction. The effect of QT-ß-CD on LuxS and motA gene expression in E. coli O157:H7 was investigated by RT-qPCR. The findings demonstrated that QT-ß-CD exhibited potent photodynamic properties and functioned as an efficient photosensitizer, causing substantial damage to E. coli O157:H7 cells. These results underscore the potential of quercetin as an antimicrobial agent for food preservation.