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1.
J Control Release ; 324: 124-133, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32430277

RESUMO

Supramolecular chemotherapy is currently a new strategy to improve the therapeutic efficacy as well as overcome the side effects of traditional chemotherapy. Herein, a supramolecular chemotherapy platform based on the pegylated guanidinium-modified calix[5]arene pentadodecyl ether (GC5A-12C) nanoassembly was prepared. Three commercially available antitumor drugs: oxaliplatin, methotrexate and chlorambucil, all showed strong binding to this GC5A-12C nanocarrier. The supramolecular nanodrugs achieved higher anticancer performances compared with free drugs in cell experiments. Furthermore, the cellular uptake mechanisms and efficacy are confirmed by fluorescence imaging.

2.
Chem Commun (Camb) ; 56(41): 5512-5515, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32296785

RESUMO

We developed a host-guest ATP responsive strategy for efficient intracellular delivery of phosphopeptides, employing a pegylated arginine clustered calix[5]arene nanocarrier system that has great capability of recognizing the phosphate moieties on peptides and penetrating the cell membrane.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32253810

RESUMO

The paradox of antioxidants is that they protect other more valuable molecules by sacrificial reactions with oxidizers. Their consequential loss in efficacy imposes great challenges to both living organisms and the food industry. Here we show that the host-guest complexation of the carefully designed positively charged amphiphilic guanidinocalix[5]arene pentadodecyl ether (GC5A-12C) and negatively charged oleic acid (OA), a well-known cell membrane antioxidant, prevents the oxidation of a monolayer of the complex at the air-water interface from two potent oxidizers, hydroxyl radicals (OH) and singlet delta oxygen (SDO). OH is generated from the gas phase and attacks from the top of the monolayer, while SDO is generated inside the monolayer and attacks amphiphiles from a lateral direction. Field-induced droplet ionization mass spectrometry results have demonstrated that the host-guest complexation is able to achieve steric shielding and to prevent both types of oxidation as a result of the tight and "sleeved in" physical arrangement, rather than the chemical reactivity, of the complexes.

4.
Chem Soc Rev ; 49(8): 2303-2315, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32181453

RESUMO

Classic prodrug strategies rely on covalent modification of active drugs to provide systems with superior pharmacokinetic properties than the parent drug and facilitate administration. Supramolecular chemistry is providing a new approach to developing prodrug-like systems, wherein the characteristics of a drug are modified in a beneficial manner by creating host-guest complexes that then permit the stimulus-induced release of the active species in a controlled manner. These complexes are termed "supramolecular prodrugs". In this review, we outline the concept of supramolecular drugs via host-guest chemistry and detail progress made in the area. This summary is designed to highlight the many advantages of supramolecular prodrugs, including ease-of-preparation, molecular-level protection, sensitive response to bio-stimuli, traceless release, and adaptability to different drugs. Limitations of the approach and opportunities for future growth are also detailed.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31981392

RESUMO

Host-guest complexation between calix[5]arene and aggregation-induced emission luminogen (AIEgen) can significantly turn off both the energy dissipation pathways of intersystem crossing and thermal deactivation, enabling the absorbed excitation energy to mostly focus on fluorescence emission. The co-assembly of calix[5]arene amphiphiles and AIEgens affords highly emissive supramolecular AIE nanodots thanks to their interaction severely restricting the intramolecular motion of AIEgens, which also show negligible generation of cytotoxic reactive oxygen species. In vivo studies with a peritoneal carcinomatosis-bearing mouse model indicate that such supramolecular AIE dots have rather low in vivo side toxicity and can serve as a superior fluorescent bioprobe for ultrasensitive fluorescence image-guided cancer surgery.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31965674

RESUMO

Calixarenes (CAs), representing the third generation of supramolecular hosts and one of the most widely studied macrocyclic scaffolds, offer (almost) unlimited possibilities due to their ease of modification, which allows one to establish a large molecular library as a material basis for diverse biomedical applications. Moreover, CAs and their derivatives engage in various non-covalent interactions for the facile recognition of guests including bioactive molecules and are also important building blocks for the fabrication of supramolecular architectures. In view of their molecular recognition and self-assembly properties, CAs are extensively applied in biosensing, bioimaging, and drug/gene delivery. Additionally, some CA derivatives exhibit biological activities and can therefore be used as new therapeutic agents. Herein, we summarize the diverse biomedical applications of CAs including in-vitro diagnosis (biosensing), in-vivo diagnosis (bioimaging), and therapy.

7.
Colloids Surf B Biointerfaces ; 186: 110676, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838269

RESUMO

Amphiphilic calixarenes are preferred to generate nano-cargos for drugs due to their stability, possibilities for modification and intrinsic host cavities. Here we are reporting the synthesis of amphiphilic calixarene and its evaluation as drug delivery system. Water soluble amphiphilic p-sulfonatocalix[6]arene was synthesized through sulfonation and lipophilic conjugation on its upper and lower rims respectively. The synthesized amphiphile self-assembled into nanostructures in the presence of Clarithromycin and FITC as model hydrophobic drugs followed by a wide range of characterization. Clarithromycin loaded self-assembled nanostructures was screened for its bactericidal potential in resistant S. pneumonia through various in-vitro assays. The amphiphilic calixarene self-assembled into polydispersed nanostructures with 136.45 ±â€¯2.41 nm mean diameter and -49.93 ±â€¯0.35 mV surface charges. The amphiphile was capable to load Clarithromycin (57.54 ±â€¯1.88 %) and fluorescent dye and was highly stable. Clarithromycin loaded nanostructures revealed significant biofilm and bacterial growth inhibition and cell destruction properties. Results authenticate calixarene amphiphile as an efficient nano-carrier for improving Clarithromycin efficacy.

8.
Molecules ; 25(1)2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31878172

RESUMO

The coumarin compound of osthole was extracted from Cnidium monnieri and identified by LC-MS and 1H- and 13C-NMR. Osthole was tested for anti-virus activity against tobacco mosaic virus (TMV) using the half-leaf method. The results showed that stronger antiviral activity on TMV infection appeared in Nicotiana glutinosa than that of eugenol and ningnanmycin, with inhibitory, protective, and curative effects of 72.57%, 70.26%, and 61.97%, respectively. Through observation of the TMV particles, we found that osthole could directly affect the viral particles. Correspondingly, the level of coat protein detected by Western blot was significantly reduced when the concentrations of osthole increased in tested plants compared to that of the control. These results suggest that osthole has anti-TMV activity and may be used as a biological reagent to control the plant virus in the half-leaf method.

9.
Nat Commun ; 10(1): 5762, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848349

RESUMO

Perfluorinated alkyl substances, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are toxic materials that are known to globally contaminate water, air, and soil resources. Strategies for the simultaneous detection and removal of these compounds are desired to address this emerging health and environmental issue. Herein, we develop a type of guanidinocalix[5]arene that can selectively and strongly bind to PFOS and PFOA, which we use to demonstrate the sensitive and quantitative detection of these compounds in contaminated water through a fluorescent indicator displacement assay. Moreover, by co-assembling iron oxide nanoparticle with the amphiphilic guanidinocalix[5]arene, we are able to use simple magnetic absorption and filtration to efficiently remove PFOS and PFOA from contaminated water. This supramolecular approach that uses both molecular recognition and self-assembly of macrocyclic amphiphiles is promising for the detection and remediation of water pollution.


Assuntos
Ácidos Alcanossulfônicos/análise , Calixarenos/química , Caprilatos/análise , Fluorcarbonetos/análise , Tensoativos/química , Poluentes Químicos da Água/análise , Absorção Fisico-Química , Ácidos Alcanossulfônicos/isolamento & purificação , Caprilatos/isolamento & purificação , Monitorização de Parâmetros Ecológicos/métodos , Poluição Ambiental/prevenção & controle , Compostos Férricos/química , Filtração/instrumentação , Filtração/métodos , Fluorcarbonetos/isolamento & purificação , Nanopartículas de Magnetita/química , Água/análise , Água/química , Poluentes Químicos da Água/isolamento & purificação , Poluição Química da Água/prevenção & controle
10.
Chem Commun (Camb) ; 55(95): 14387-14390, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31723950

RESUMO

We designed a tandem stimuli-responsive assembly based on a guanidinium-modified calix[5]arene (GC5A-6C) and eosin Y modified hyaluronic acid (EY-HA), which showed hyaluronidase-triggered disassembly and ATP-activated release of EY. Both hyaluronidase and ATP are tumor biomarkers, and therefore, the present system shows potential in precision delivery with respect to tumor phototheranostics.


Assuntos
Trifosfato de Adenosina/metabolismo , Calixarenos/metabolismo , Amarelo de Eosina-(YS)/metabolismo , Guanidina/metabolismo , Ácido Hialurônico/metabolismo , Hialuronoglucosaminidase/metabolismo , Trifosfato de Adenosina/química , Biomarcadores Tumorais/química , Biomarcadores Tumorais/metabolismo , Calixarenos/química , Amarelo de Eosina-(YS)/química , Guanidina/química , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase/química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/metabolismo , Polímeros/química , Polímeros/metabolismo , Nanomedicina Teranóstica , Microambiente Tumoral
11.
J Am Chem Soc ; 141(51): 20137-20145, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31739668

RESUMO

The membrane transport mechanisms of cell-penetrating peptides (CPPs) are still controversial, and reliable assays to report on their internalization in model membranes are required. Herein, we introduce a label-free, fluorescence-based method to monitor membrane transport of peptides in real time. For this purpose, a macrocyclic host and a fluorescent dye forming a host-dye reporter pair are encapsulated inside phospholipid vesicles. Internalization of peptides, which can bind to the supramolecular host, leads to displacement of the dye from the host, resulting in a fluorescence change that signals the peptide uptake and, thus, provides unambiguous evidence for their transport through the membrane. The method was successfully validated with various established CPPs, including the elusive peptide TP2, in the presence of counterion activators of CPPs, and with a calixarene-based supramolecular membrane transport system. In addition, transport experiments with encapsulated host-dye reporter pairs are not limited to large unilamellar vesicles (LUVs) but can also be used with giant unilamellar vesicles (GUVs) and fluorescence microscopy imaging.

12.
Theranostics ; 9(16): 4624-4632, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367245

RESUMO

Detection and quantification of trimethylamine N-oxide (TMAO), a metabolite from gut microbial, is important for the disease diagnosis such as atherosclerosis, thrombosis and colorectal cancer. In this study, a novel method was established for the sensing and quantitative detection of TMAO via molecular recognition of guanidinium-modified calixarene from complex matrix. Methods: Various macrocycles were tested for their abilities to serve as an artificial TMAO receptor. Using the optimized receptor, we developed an indicator displacement assay (IDA) for the facile fluorescence detection of TMAO. The quantification of TMAO was accomplished by the established calibration line after excluding the interference from the various interfering substances in artificial urine. Results: Among various macrocycles, water-soluble guanidinium-modified calix[5]arene (GC5A), which binds TMAO in submicromolar-level, was identified as the optimal artificial receptor for TMAO. With the aid of the GC5A•Fl (fluorescein) reporter pair, TMAO fluorescence "switch-on" sensing was achieved by IDA. The fluorescence intensity increased linearly with the elevated TMAO concentration. The detection was not significantly interfered by the various interfering substances. TMAO concentration in artificial urine was quantified using a calibration line with a detection limit of 28.88 ± 1.59 µM, within the biologically relevant low µM range. Furthermore, the GC5A•Fl reporter pair was successfully applied in analyzing human urine samples, by which a significant difference in fluorescence response was observed between the [normal + TMAO] and normal group. Conclusion: The proposed supramolecular approach provides a facile, low-cost and sensitive method for TMAO detection, which shows promise for tracking TMAO excretion in urine and studying chronic disease progression in humans.

13.
Beilstein J Org Chem ; 15: 1394-1406, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293689

RESUMO

We herein describe the comprehensive investigation of the complexation behavior of a guanidinium-modified calix[5]arene pentaisohexyl ether (GC5A) with a variety of typical luminescent dyes. Fluorescein, eosin Y, rose bengal, tetraphenylporphine sulfonate and sulfonated aluminum phthalocyanine were employed as classical aggregation-induced quenching dyes. 2-(p-Toluidinyl)naphthalene-6-sulfonic acid and 1-anilinonaphthalene-8-sulfonic acid were selected as representatives of intramolecular charge-transfer dyes. Phosphated tetraphenylethylene was involved as the classical aggregation-induced emission dye. Sulfonated acedan representing one example of two-photon fluorescent probes, was also investigated. A ruthenium(II) complex with carboxylated bipyridyl ligands was included as a representative candidate of luminescent transition-metal complexes. We determined the association constants of the GC5A-dye complexes by fluorescence titration and discuss the complexation-induced photophysical changes. In addition, a comparison of the complexation behavior of GC5A with that of other macrocycles and potential applications according to the diverse photophysical responses are provided.

14.
Molecules ; 24(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174300

RESUMO

In this study, two phenol compounds, magnolol and honokiol, were extracted from Magnolia officinalis and identified by LC-MS, 1H- and 13C-NMR. The magnolol and honokiol were shown to be effective against seven pathogenic fungi, including Alternaria alternata (Fr.) Keissl, Penicillium expansum (Link) Thom, Alternaria dauci f.sp. solani, Fusarium moniliforme J. Sheld, Fusarium oxysporum Schltdl., Valsa mali Miyabe & G. Yamada, and Rhizoctonia solani J.G. Kühn, with growth inhibition of more than 57%. We also investigated the mechanisms underlying the potential antifungal activity of magnolol and honokiol. The results showed that they inhibited the growth of A. alternata in a dose-dependent manner. Moreover, magnolol and honokiol treatment resulted in distorted mycelia and increased the cell membrane permeability of A. alternata, as determined by conductivity measurements. These results suggest that magnolol and honokiol are potential antifungal agents for application against plant fungal diseases.


Assuntos
Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Lignanas/química , Lignanas/farmacologia , Magnolia/efeitos dos fármacos , Doenças das Plantas/microbiologia , Alternaria/efeitos dos fármacos , Alternaria/patogenicidade , Antifúngicos/química , Antifúngicos/farmacologia , Magnolia/química , Tabaco/efeitos dos fármacos , Tabaco/microbiologia
15.
Theranostics ; 9(11): 3094-3106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244943

RESUMO

Gene therapy, with an important role in biomedicine, often requires vectors for gene condensation in order to avoid degradation, improve membrane permeation, and achieve targeted delivery. Macrocyclic molecules are a family of artificial receptors that can selectively bind a variety of guest species. Amphiphilic macrocycles, particularly those bearing cationic charges and their various assemblies represent a new class of promising non-viral vectors with intrinsic advantages in gene condensation and delivery. The most prominent examples include amphiphilic cyclodextrins, calixarenes and pillararenes. Herein, we systemically reviewed reported assemblies of amphiphilic macrocycles for gene delivery and therapy. The advantages and disadvantages of each type of macrocyclic amphiphiles for gene delivery, as well as the perspectives on the future development of this area are discussed.

16.
Angew Chem Int Ed Engl ; 58(8): 2377-2381, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30628146

RESUMO

Hypoxia plays crucial roles in many diseases and is a central target for them. Present hypoxia imaging is restricted to the covalent approach, which needs tedious synthesis. In this work, a new supramolecular host-guest approach, based on the complexation of a hypoxia-responsive macrocycle with a commercial dye, is proposed. To exemplify the strategy, a carboxyl-modified azocalix[4]arene (CAC4A) was designed that binds to rhodamine 123 (Rho123) and quenches its fluorescence. The azo groups of CAC4A were selectively reduced under hypoxia, leading to the release of Rho123 and recovery of its fluorescence. The noncovalent strategy was validated through hypoxia imaging in living cells treated with the CAC4A-Rho123 reporter pair.

17.
Nat Chem ; 11(1): 86-93, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30455432

RESUMO

Heteromultivalency, which involves the simultaneous interactions of more than one type of ligand with more than one type of receptor, is ubiquitous in living systems and provides a powerful strategy to improve the binding efficiency of heterotopic species such as proteins and membranes. However, the design and development of artificial heteromultivalent receptors is still challenging owing to tedious synthesis processes and the need for precise control over the spatial arrangement of the binding sites. Here, we have designed a heteromultivalent platform by co-assembling cyclodextrin and calixarene amphiphiles, so that two orthogonal, non-covalent binding sites are distributed on the surface of the co-assembly. Binding with model peptides shows a synergistic effect of the two receptors, (hetero)multivalency and self-adaptability. The co-assembly shows promise for inhibition of the fibrillation of amyloid-ß peptides and the dissolution of amyloid-ß fibrils, substantially reducing amyloid cytotoxicity. This self-assembled heteromultivalency concept is easily amenable to other ensembles and targets, so that versatile biomedical applications can be envisaged.


Assuntos
Amiloide , Calixarenos , Ciclodextrinas , Peptídeos , Amiloide/química , Amiloide/metabolismo , Peptídeos beta-Amiloides , Animais , Calixarenos/química , Calixarenos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Ciclodextrinas/química , Ciclodextrinas/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Células PC12 , Fragmentos de Peptídeos , Peptídeos/química , Peptídeos/metabolismo , Ratos
18.
Bioresour Technol ; 271: 118-124, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30265951

RESUMO

The aim of this work was to reduce the algae-residue emission and make use of cane molasses as fermentation materials for docosahexaenoic acid (DHA) fermentaion by Schizochytrium sp., which further could cut the cost of DHA production. Algae-residue and cane molasses were respectively used as nitrogen and carbon sources to replace yeast extract and glucose. A significant DHA yield of 18.58 g/L was obtained using algae-residue, while cane molasses could not be used well as sole carbon source due to the presence of undesirable substance. A two-stage culture strategy with glucose followed by pretreated cane molasses as carbon source was developed, resulting in a final DHA yield of 15.22 g/L. This study therefore offers an economical and green strategy for DHA production by Schizochytrium sp.


Assuntos
Bengala , Ácidos Docosa-Hexaenoicos/biossíntese , Estramenópilas/metabolismo , Carbono/metabolismo , Fermentação , Glucose/metabolismo , Melaço , Nitrogênio/metabolismo
19.
Nanoscale ; 10(39): 18829-18834, 2018 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-30277253

RESUMO

Portable visual detection systems for environmental monitoring or diagnostic purposes are eagerly anticipated in low-resource settings. Inexpensive device requirements and visualization are key challenges for the development of any portable analysis system. We report herein a new strategy for developing portable rapid ion detection technology by the coupling of topochemical polymerization and supramolecular (SM) self-assembly. The rapid sol-gel or gel-sol phase transition of SM hydrogels has been widely applied for the detection of many important analytes including metal ions. However, one problem that remains is the difficulty inaccurately quantifying the degree of self-assembly with the naked eye. To address this problem, we designed a diacetylene-grafted peptide that can be polymerized following self-assembly into a hydrogel triggered by zinc ions. Before adding zinc ions, the molecules dissolved well in aqueous solution and arranged randomly, and were unable to be polymerized through UV light irradiation. After mixing with zinc ions, the peptide chelated with zinc ions immediately and self-assembled into a SM hydrogel. The molecules arranged orderly and could be easily polymerized through irradiation of a hand-held UV lamp in less than 2 minutes. The hydrogel showed a quick and sharp chromatic change from colorless to dark blue, which allowed the quantification of self-assembly (i.e. concentration of zinc ions) with the naked eye. In addition, the monomers were insensitive to light, pH and temperature changes, which is a highly desired characteristic in practical applications.

20.
Beilstein J Org Chem ; 14: 1840-1845, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30112088

RESUMO

Based on the indicator displacement assay (IDA) approach, we herein report the fluorescence "switch-on" sensing and quantitative detection of bisphosphonates (BPs), a class of drugs extensively used in the treatment of patients with various skeletal diseases. Guanidinium-modified calix[5]arene (GC5A) affords strong binding on the micromolar to nanomolar level towards BPs dominantly via multiple salt bridge interactions, which was evaluated by fluorescence competitive titrations. Fluorescent IDA enables the highly sensitive and label-free detection of BPs in buffer solution, and more importantly, in artificial urine. Calibration lines were therefore set up in untreated artificial urine, allowing for quantifying the concentrations of BPs in the biologically relevant low range.

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