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1.
Artigo em Inglês | MEDLINE | ID: mdl-38752799

RESUMO

An ideal vehicle with a high transfection efficiency is crucial for gene delivery. In this study, a type of cationic carbon dot (CCD) known as APCDs were first prepared with arginine (Arg) and pentaethylenehexamine (PEHA) as precursors and conjugated with oleic acid (OA) for gene delivery. By tuning the mass ratio of APCDs to OA, APCDs-OA conjugates, namely, APCDs-0.5OA, APCDs-1.0OA, and APCDs-1.5OA were synthesized. All three amphiphilic APCDs-OA conjugates show high affinity to DNA through electrostatic interactions. APCDs-0.5OA exhibit strong binding with small interfering RNA (siRNA). After being internalized by Human Embryonic Kidney (HEK 293) and osteosarcoma (U2OS) cells, they could distribute in both the cytoplasm and the nucleus. With APCDs-OA conjugates as gene delivery vehicles, plasmid DNA (pDNA) that encodes the gene for the green fluorescence protein (GFP) can be successfully delivered in both HEK 293 and U2OS cells. The GFP expression levels mediated by APCDs-0.5OA and APCDs-1.0OA are ten times greater than that of PEI in HEK 293 cells. Furthermore, APCDs-0.5OA show prominent siRNA transfection efficiency, which is proven by the significantly downregulated expression of FANCA and FANCD2 proteins upon delivery of FANCA siRNA and FANCD2 siRNA into U2OS cells. In conclusion, our work demonstrates that conjugation of CCDs with a lipid structure such as OA significantly improves the gene transfection efficiency, providing a new idea about the designation of nonviral carriers in gene delivery systems.

2.
Funct Plant Biol ; 512024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38560925

RESUMO

Continuous increasing leaf photosynthesis may enhance plant yield. As an evolutionary property, plants use less photosynthetic capacity than is theoretically possible. Plant nanobionics is a bioengineering field that improves plant functions using nanoparticles. We applied orange carbon dots (o-CDs) onto the foliage of green beans (Phaseolus vulgaris ) grown in hydroponics to improve their photosynthetic performance and CO2 assimilation. Photosynthesis parameters, photosynthetic pigments content, total phenolic content (TPC) and antioxidative activity (TAA) were measured. Results show that photosynthetic pigments remained unchanged, while photosynthesis was improved. Both o-CDs concentrations decreased TPC and TAA. The light response curve showed higher CO2 assimilation at both o-CDs concentrations, particularly at lower light intensity. Correlation analysis confirmed increased CO2 binding and assimilation at 1mg L-1 . This study demonstrated the potential of using o-CDs as a safe biostimulator through photosynthesis increase and CO2 assimilation without toxic effects on plants. This may stimulate yield increase that paves the way for their agricultural application.


Assuntos
Dióxido de Carbono , Phaseolus , Dióxido de Carbono/metabolismo , Phaseolus/metabolismo , Carbono , Fotossíntese , Luz , Plantas/metabolismo
3.
Small ; 20(18): e2309283, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38230862

RESUMO

The appeal of carbon dots (CDs) has grown recently, due to their established biocompatibility, adjustable photoluminescence properties, and excellent water solubility. For the first time in the literature, copper chlorophyllin-based carbon dots (Chl-D CDs) are successfully synthesized. Chl-D CDs exhibit unique spectroscopic traits and are found to induce a Fenton-like reaction, augmenting photodynamic therapy (PDT) efficacies via ferroptotic and apoptotic pathways. To bolster the therapeutic impact of Chl-D CDs, a widely used cancer drug, temozolomide, is linked to their surface, yielding a synergistic effect with PDT and chemotherapy. Chl-D CDs' biocompatibility in immune cells and in vivo models showed great clinical potential.Proteomic analysis was conducted to understand Chl-D CDs' underlying cancer treatment mechanism. The study underscores the role of reactive oxygen species formation and pointed toward various oxidative stress modulators like aldolase A (ALDOA), aldolase C (ALDOC), aldehyde dehydrogenase 1B1 (ALDH1B1), transaldolase 1 (TALDO1), and transketolase (TKT), offering a deeper understanding of the Chl-D CDs' anticancer activity. Notably, the Chl-D CDs' capacity to trigger a Fenton-like reaction leads to enhanced PDT efficiencies through ferroptotic and apoptotic pathways. Hence, it is firmly believed that the inherent attributes of Chl-CDs can lead to a secure and efficient combined cancer therapy.


Assuntos
Carbono , Clorofilídeos , Ferroptose , Carbono/química , Humanos , Ferroptose/efeitos dos fármacos , Animais , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Ferro/química , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/química , Apoptose/efeitos dos fármacos
4.
Sci Total Environ ; 916: 170176, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38244620

RESUMO

Carbon nanoparticles, or carbon dots, can have many beneficial uses. However, we must consider whether they may have any potential negative side effects on wildlife or the ecosystem when these particles end up in wastewater. Early development stages of amphibians are particularly sensitive to contaminants, and exposure to carbon dots could disrupt their development and cause morbidity or death. Past studies have investigated short-term exposure to certain types of nanoparticles, but if these particles get into wastewater exposure may not be short term. Therefore, we tested whether chronic exposure to different concentrations of carbon dots affects the growth, metamorphosis, and telomere length of Cuban tree frog (Osteopilus septentrionalis) tadpoles. We exposed 12 groups of five tadpoles each to different concentrations of carbon dots and a control for three months and tracked survival, growth and metamorphosis. We used carbon nitride dots approximately 2 nm in size at concentrations of 0.01 mg/ml and 0.02 mg/ml, known to interrupt development in zebrafish embryos. After three months, we measured telomere length from tissue samples. We found no difference in tadpole survivorship, growth, development rate, or telomere length among any of the groups, suggesting that carbon dots at these concentrations do not disrupt tadpole development.


Assuntos
Ecossistema , Nitrilas , Águas Residuárias , Animais , Larva , Peixe-Zebra , Metamorfose Biológica , Anuros , Carbono/toxicidade , Telômero
5.
Colloids Surf B Biointerfaces ; 234: 113719, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181692

RESUMO

In this new study, we present an intriguing development in the field of theranostics: the simplistic self-assembly of red-emissive amphiphilic porphyrin-like carbon dots (P-CDs). By harnessing their exceptional photophysical properties, we have revealed a strong candidate as the ideal photosensitizer (PS) for applications, particularly in the realm of imaging. Spanning a remarkable size average between 1-4 nm, these particles exhibit both highly stable and unparalleled emission characteristics between 650 and 715 nm in water in comparison to current carbon dots (CDs) available. Lastly, these CDs were fairly non-toxic when tested against normal human cell lines as well as were found to have favorable imaging capabilities in zebrafish embryo.


Assuntos
Pontos Quânticos , Água , Humanos , Animais , Carbono , Peixe-Zebra , Linhagem Celular
6.
J Colloid Interface Sci ; 650(Pt B): 1619-1637, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37494859

RESUMO

Over time, the interest in developing stable photosensitizers (PS) which both absorb and emit light in the red region (650 and 950 nm) has gained noticeable interest. Recently, carbon dots (CDs) have become the material of focus to act as a PS due to their high extinction coefficient, low cytotoxicity, and both high photo and thermal stability. In this work, a Federal and Drug Association (FDA) approved Near Infra-Red (NIR) organic fluorophore used for photo-imaging, indocyanine green (ICG), has been explored as a precursor to develop water-soluble red emissive CDs which possess red emission at 697 nm. Furthermore, our material was found to yield favorable red-imaging capabilities of glioblastoma stem-like cells (GSCs) meanwhile boasting low toxicity. Additionally with post modifications, our CDs have been found to have selectivity towards tumors over healthy tissue as well as crossing the blood-brain barrier (BBB) in zebrafish models.


Assuntos
Glioblastoma , Pontos Quânticos , Animais , Carbono , Glioblastoma/diagnóstico por imagem , Peixe-Zebra , Corantes Fluorescentes
7.
Int J Mol Sci ; 24(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37298513

RESUMO

Pediatric brain tumors remain a significant source of morbidity and mortality. Though developments have been made in treating these malignancies, the blood-brain barrier, intra- and inter-tumoral heterogeneity, and therapeutic toxicity pose challenges to improving outcomes. Varying types of nanoparticles, including metallic, organic, and micellar molecules of varying structures and compositions, have been investigated as a potential therapy to circumvent some of these inherent challenges. Carbon dots (CDs) have recently gained popularity as a novel nanoparticle with theranostic properties. This carbon-based modality is highly modifiable, allowing for conjugation to drugs, as well as tumor-specific ligands in an effort to more effectively target cancerous cells and reduce peripheral toxicity. CDs are being studied pre-clinically. The ClinicalTrials.gov site was queried using the search terms: brain tumor and nanoparticle, liposome, micelle, dendrimer, quantum dot, or carbon dot. At the time of this review, 36 studies were found, 6 of which included pediatric patients. Two of the six studies investigated nanoparticle drug formulations, whereas the other four studies were on varying liposomal nanoparticle formulations for the treatment of pediatric brain tumors. Here, we reviewed the context of CDs within the broader realm of nanoparticles, their development, promising pre-clinical potential, and proposed future translational utility.


Assuntos
Neoplasias Encefálicas , Nanopartículas , Pontos Quânticos , Humanos , Criança , Sistemas de Liberação de Medicamentos , Carbono/uso terapêutico , Carbono/química , Neoplasias Encefálicas/tratamento farmacológico , Lipossomos , Nanopartículas/uso terapêutico , Nanopartículas/química , Nanomedicina Teranóstica
8.
Molecules ; 28(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36838742

RESUMO

In this work, a NIR emitting dye, p-toluenesulfonate (IR-813) was explored as a model precursor to develop red emissive carbon dots (813-CD) with solvatochromic behavior with a red-shift observed with increasing solvent polarity. The 813-CDs produced had emission peaks at 610 and 698 nm, respectively, in water with blue shifts of emission as solvent polarity decreased. Subsequently, 813-CD was synthesized with increasing nitrogen content with polyethyleneimine (PEI) to elucidate the change in band gap energy. With increased nitrogen content, the CDs produced emissions as far as 776 nm. Additionally, a CD nanocomposite polyvinylpyrrolidone (PVP) film was synthesized to assess the phenomenon of solid-state fluorescence. Furthermore, the CDs were found to have electrochemical properties to be used as an additive doping agent for PVP film coatings.


Assuntos
Carbono , Pontos Quânticos , Solventes/química , Carbono/química , Pontos Quânticos/química , Corantes Fluorescentes/química , Nitrogênio/química
9.
Int J Pharm ; 638: 122740, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36804524

RESUMO

The eye is one of the most important organs in the human body providing critical information on the environment. Many corneal diseases can lead to vision loss affecting the lives of people around the world. Ophthalmic drug delivery has always been a major challenge in the medical sciences. Since traditional methods are less efficient (∼5%) at delivering drugs to ocular tissues, contact lenses have generated growing interest in ocular drug delivery due to their potential to enhance drug bioavailability in ocular tissues. The main techniques used to achieve sustained release are discussed in this review, including soaking in drug solutions, incorporating drug into multilayered contact lenses, use of vitamin E barriers, molecular imprinting, nanoparticles, micelles and liposomes. The most clinically relevant results on different eye pathologies are presented. In addition, this review summarizes the benefits of contact lenses over eye drops, strategies for incorporating drugs into lenses to achieve sustained release, results of in vitro and in vivo studies, and recent advances in the commercialization of therapeutic contact lenses for allergic conjunctivitis.


Assuntos
Lentes de Contato Hidrofílicas , Oftalmopatias , Humanos , Preparações de Ação Retardada/uso terapêutico , Administração Oftálmica , Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico , Córnea
10.
J Colloid Interface Sci ; 639: 180-192, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36805743

RESUMO

Carbon dots (CDs) have attracted much attention due to their excellent properties and applications, especially the use for gene delivery. Considering the risks and concerns involved in the use of viral vectors for gene delivery in vivo, non-viral vectors such as CDs have gradually become an ideal alternative due to their biocompatibility and low toxicity. Therefore, in this study, the potential to apply CDs as a non-viral vector for gene delivery was investigated. The CDs were prepared using citric acid and pentaethylenehexamine (PEHA) as precursors via a one-step microwave-mediated approach. The optical, structural, and morphological properties of PEHA-derived CDs (PCDs) were characterized by ultra-violet spectroscopy (UV-vis), photoluminescence (PL), Fourier Transform Infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), zeta potential, circular dichroism spectrometry, atomic force (AFM) and transmission electron microscopies (TEM). The analysis demonstrated that the as-prepared PCDs were rich in amine groups and were positively charged. Subsequently, gel retardation assay showed that PCDs could non-covalently bind with DNA at a mass ratio of 2:1 (PCDs: DNA). Additionally, PCDs possessed a tremendously lower cytotoxicity compared with polyethylenimine (PEI), a popular precursor/dopant for many CDs preparations, and their plasmid composite showed a high transfection efficiency. Meanwhile, PCDs were also observed to cross the blood-brain barrier (BBB) by using a zebrafish model. In conclusion, these results significantly indicate that PCDs are a potential non-viral nucleic acid/gene vector to gene therapy. Also, PCDs can be utilized in drug delivery for treating brain diseases, such as Alzheimer's disease and brain tumors.


Assuntos
Pontos Quânticos , Animais , Pontos Quânticos/química , Carbono/química , Peixe-Zebra , Terapia Genética , DNA
11.
J Colloid Interface Sci ; 637: 193-206, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36701865

RESUMO

Nucleus targeting is tremendously important in cancer therapy. Cationic carbon dots (CCDs) are potential nanoparticles which might enter cells and penetrate nuclear membranes. Although some CCDs have been investigated in nucleus targeting and applied in nuclear imaging, the CCDs derived from drugs, that are able to target the nucleus, bind with DNA and inhibit the growth of cancer cells have not been reported. In this project, 1, 2, 4, 5-benzenetetramine (Y15, a focal adhesion kinase inhibitor) derived cationic carbon dots (Y15-CDs) were prepared via a hydrothermal approach utilizing Y15, folic acid and 1,2-ethylenediamine as precursors. Based on the structural, optical, and morphologic characterizations, Y15-CDs possess rich amine groups and nitrogen in structure, an excitation-dependent photoluminescence emission, and a small particle size of 2 to 4 nm. The DNA binding experiments conducted through agarose gel electrophoresis, UV-vis absorption, fluorescence emission, and circular dichroism spectroscopies, prove that Y15-CDs might bind with DNA via electrostatic interactions and partially intercalative binding modes. In addition, the cell imaging and cytotoxicity studies in human foreskin fibroblasts (HFF), prostate cancer (PC3) and osteosarcoma cells (U2OS) indicate the nucleus targeting and anticancer abilities of Y15-CDs. Most interestingly, Y15-CDs exhibit a higher cytotoxicity to cancer cells (PC3 and U2OS) than to normal cells (HFF), inferring that Y15-CDs might be potentially applied in cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Pontos Quânticos , Masculino , Humanos , Pontos Quânticos/química , Carbono/farmacologia , Carbono/química , Nanopartículas/química , Espectrometria de Fluorescência , DNA/metabolismo , Corantes Fluorescentes/química
12.
J Colloid Interface Sci ; 630(Pt A): 306-321, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36244103

RESUMO

Carbon dots (CDs) from glucose were synthesized using two of the most common bottom-up methods, namely, microwave assisted (MW) and hydrothermal carbonization (HT). Synthetic parameters such as reaction time, temperature, and precursor concentration were changed to study the effects of each parameter on CD size, structure, surface functionalities, charge, photoluminescence behavior, quantum yield, cytotoxicity, blood-brain barrier (BBB) crossing ability and bioimaging. A detailed analysis is performed to compare the structure and properties of the CDs synthesized in ten different conditions. We show that the synthesis route drastically changes the structure, properties, and related functions of glucose-derived CDs yielding two different subtypes of CDs. Surprisingly, CDs that was synthesized via HT method showed specific anticancer activity against a neuroblastoma cell line while being non-toxic towards healthy cell lines, indicating significant potential for therapeutic applications. CDs synthesized via MW crosses the BBB in zebrafish and rat models, and accumulates in neurons. CDs synthesized via MW method showed high biocompatibility and a great potential to be used for bioimaging applications in vitro and in vivo targeting neurons. Finally, a formation mechanism of CDs is proposed for both HT and MW synthesis routes.


Assuntos
Neuroblastoma , Pontos Quânticos , Ratos , Animais , Carbono/química , Pontos Quânticos/química , Micro-Ondas , Nitrogênio/química , Peixe-Zebra , Linhagem Celular , Neuroblastoma/tratamento farmacológico , Glucose
13.
Nanoscale ; 14(47): 17607-17624, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36412202

RESUMO

The carbon nitride dot (CND) is an emerging carbon-based nanomaterial. It possesses rich surface functional moieties and a carbon nitride core. Spectroscopic data have demonstrated the analogy between CNDs and cytosine/uracil. Recently, it was found that CNDs could interrupt the normal embryogenesis of zebrafish. Modifying CNDs with various nucleobases, especially cytosine, further decreased embryo viability and increased deformities. Physicochemical property characterization demonstrated that adenine- and cytosine-incorporated CNDs are similar but different from guanine-, thymine- and uracil-incorporated CNDs in many properties, morphology, and structure. To investigate the embryogenesis interruption at the cellular level, bare and different nucleobase-incorporated CNDs were applied to normal and cancerous cell lines. A dose-dependent decline was observed in the viability of normal and cancerous cells incubated with cytosine-incorporated CNDs, which matched results from the zebrafish embryogenesis experiment. In addition, nucleobase-incorporated CNDs were observed to enter cell nuclei, demonstrating a possibility of CND-DNA interactions. CNDs modified by complementary nucleobases could bind each other via hydrogen bonds, which suggests nucleobase-incorporated CNDs can potentially bind the complementary nucleobases in a DNA double helix. Nonetheless, neither bare nor nucleobase-incorporated CNDs were observed to intervene in the amplification of the zebrafish polymerase-alpha 1 gene in quantitative polymerase chain reactions. Thus, in conclusion, the embryogenesis interruption by bare and nucleobase-incorporated CNDs might not be a consequence of CND-DNA interactions during DNA replication. Instead, CND-Ca2+ interactions offer a plausible mechanism that hindered cell proliferation and zebrafish embryogenesis originating from disturbed Ca2+ homeostasis by CNDs. Eventually, the hypothesis that raw or nucleobase-incorporated CNDs can be nucleobase analogs proved to be invalid.


Assuntos
Citosina , Peixe-Zebra , Animais , Uracila
14.
J Phys Chem B ; 126(51): 10777-10796, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36395361

RESUMO

Carbon dots (CDs) are one of the most versatile nanomaterials discovered in the 21st century. They possess many properties and thus hold potentials in diverse applications. While an increasing amount of attention has been given to these novel nanoparticles, the broad scientific community is actively engaged in exploring their limits. Recent studies on the fractionalization and assembly of CDs further push the limits beyond just CDs and demonstrate that CDs are both a mixture of heterogeneous fractions and promising building blocks for assembly of large carbon-based materials. With CDs moving forward toward both microscopic and macroscopic levels, a good understanding of the structure-property-activity relationships is essential to forecasting the future of CDs. Hence, in this Perspective, structure-property-activity relationships are highlighted based on the repeatedly verified findings in CDs. In addition, studies on CD fractionalization and assembly are briefly summarized in this Perspective. Eventually, these structure-property-activity relationships and controllability are essential for the development of CDs with desired properties for various applications especially in photochemistry, electrochemistry, nanomedicine, and surface chemistry. In summary, in our opinion, since 2004 until the present, history has witnessed a great development of CDs although there is still some room for more studies. Also, considering many attractive properties, structure-property-activity relationships, and the building block nature of CDs, a variety of carbon-based materials of interest can be constructed from CDs with control. They can help reduce blind trials in the development of carbon-based materials, which is of great significance in materials science, chemistry, and any fields related to the applications.


Assuntos
Nanopartículas , Nanoestruturas , Pontos Quânticos , Carbono/química , Nanopartículas/química , Pontos Quânticos/química
15.
Pharmaceutics ; 14(7)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35890360

RESUMO

The current prognosis for glioblastoma is dismal. Treatment-resistant glioblastoma stem cells (GSCs) and the failure of most drugs to reach therapeutic levels within the tumor remain formidable obstacles to successful treatment. Chalcones are aromatic ketones demonstrated to reduce malignant properties in cancers including glioblastoma. Nanomedicines can increase drug accumulation and tumor cell death. Carbon-dots are promising nanocarriers that can be easily functionalized with tumor-targeting ligands and anti-cancer drugs. Therefore, we synthesized a series of 4'-amino chalcones with the rationale that the amino group would serve as a "handle" to facilitate covalent attachment to carbon-dots and tested their cytotoxicity toward GSCs. We generated 31 chalcones (22 4'-amino and 9 4' derivatives) including 5 novel chalcones, and found that 13 had an IC50 below 10 µM in all GSC lines. After confirming that the 4-amino group was not part of the active pharmacophore, chalcones were attached to transferrin-conjugated carbon-dots. These conjugates were significantly more cytotoxic than the free chalcones, with the C-dot-transferrin-2,5, dimethoxy chalcone conjugate inducing up to 100-fold more GSC death. Several of the tested chalcones represent promising lead compounds for the development of novel anti-GSC drugs. Furthermore, designing amino chalcones for carbon-dot mediated drug delivery is a rational and effective methodology.

16.
ACS Appl Bio Mater ; 5(7): 3300-3309, 2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35771033

RESUMO

Neuroblastoma (NB) is a pediatric malignancy affecting the peripheral nervous system. Despite recent advancements in treatment, many children affected with NB continue to submit to this illness, and new therapeutic strategies are desperately needed. In recent years, studies of carbon dots (CDs) as nanocarriers have mostly focused on the delivery of anticancer agents because of their biocompatibility, good aqueous dissolution, and photostability. Their fluorescence properties, surface functionalities, and surface charges differ on the basis of the type of precursors used and the synthetic approach implemented. At present, most CDs are used as nanocarriers by directly linking them either covalently or electrostatically to drug molecules. Though most modern CDs are synthesized from large carbon macromolecules and conjugated to anticancerous drugs, constructing CDs from the anticancerous drugs and precursors themselves to increase antitumoral activity requires further investigation. Herein, CDs were synthesized using difluoromethylornithine (DFMO), an irreversible ornithine decarboxylase inhibitor commonly used in high-risk neuroblastoma treatment regiments. In this study, NB cell lines, SMS-KCNR and SK-N-AS, were treated with DFMO, the newly synthesized DFMO CDs, and conventional DFMO conjugated to black carbon dots. Bioimaging was done to determine the cellular localization of a fluorescent drug over time. The mobility of DNA mixed with DFMO CDs was evaluated by gel electrophoresis. DFMO CDs were effectively synthesized from DFMO precursor and characterized using spectroscopic methods. The DFMO CDs effectively reduced cell viability with increasing dose. The effects were dramatic in the N-MYC-amplified line SMS-KCNR at 500 µM, which is comparable to high doses of conventional DFMO at a 60-fold lower concentration. In vitro bioimaging as well as DNA electrophoresis showed that synthesized DFMO CDs were able to enter the nucleus of neuroblastoma cells and neuronal cells and interact with DNA. Our new DFMO CDs exhibit a robust advantage over conventional DFMO because they induce comparable reductions in viability at a dramatically lower concentration.


Assuntos
Antineoplásicos , Neuroblastoma , Antineoplásicos/farmacologia , Carbono/farmacologia , Criança , Eflornitina/farmacologia , Humanos , Neuroblastoma/diagnóstico por imagem , Inibidores da Ornitina Descarboxilase/uso terapêutico
17.
Nanoscale ; 14(27): 9686-9701, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35766148

RESUMO

Carbon Dots (CDs) have recently attracted a considerable amount of attention thanks to their well-documented biocompatibility, tunable photoluminescence, and excellent water solubility. However, CDs need further analysis before their potential use in clinical trials. Previously, we reported a new type of carbon nitride dot (CND) that displayed selective cancer uptake traits attributed to structural resemblances between CNDs and glutamine. Here, the effects of surface structural differences on the cellular uptake of CNDs are further investigated to understand their selective cancer cell uptake trend. Beyond enhanced drug loading on modified CNDs, our cytotoxicity, western blotting and bioimaging studies proposed that modified CNDs' cellular uptake mechanism is thoroughly linked with ASCT2 and LAT1 transporters. Therefore, CNDs have a promising trait of selective cancer cell targeting by utilizing highly expressed transporters on cancer cells. Additionally, drug loaded CNDs exhibited improved anti-cancer efficacies towards cancer cells along with good non-tumor biocompatibilities.


Assuntos
Carbono , Neoplasias , Carbono/química , Humanos , Neoplasias/tratamento farmacológico , Nitrilas/química
18.
Anal Sci ; 38(7): 935-940, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35633482

RESUMO

Protein's magic function stems from its structure and various analytical techniques have been developed for it. Among proteins, membrane proteins are encoded 20-30% of genomes, whereas cause challenges for many analytical techniques. For example, lots of membrane proteins cannot form single crystal structure required by X-ray crystallography. As for NMR, the measurements were hindered by the low tumbling rates of membrane (i.e., phospholipid bilayers) where membrane proteins exist. In addition, membrane proteins usually lay parallel to the surface of phospholipid bilayers or form transmembrane structure. No matter parallel or perpendicular to phospholipid bilayers surface, membrane proteins form monolayer structure which is also difficult for X-ray and NMR to provide high-resolution results. Because NMR and X-ray crystallography are the two major analytical techniques to address protein's structure, membrane proteins only contribute 2.4% to the solved protein databank. Surface FT-IR techniques can evaluate the conformation and orientation of membrane proteins by amide I band. Specifically for α-helical peptides/proteins, the orientation of the axis is critical to decide whether proteins form transmembrane structure. Notice that the traditional FT-IR can only provide "low-resolution" results. Here, 13C isotope was introduced into the nonamyloid component (NAC), which spans residues 61-95 of α-synuclein (α-syn). Then, p-polarized multiple-angle incidence resolution spectrometry (pMAIRS) was used to determine the orientation of a specific residue of α-helical NAC in monolayer. In general, pMAIRS is a novel technique to work complementary with X-ray and NMR to address membrane peptides/proteins structure with high resolution even in monolayer.


Assuntos
Bicamadas Lipídicas , alfa-Sinucleína , Incidência , Bicamadas Lipídicas/química , Proteínas de Membrana , Peptídeos/química , Fosfolipídeos , Conformação Proteica , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , alfa-Sinucleína/química
19.
Carbon N Y ; 193: 1-16, 2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35463198

RESUMO

Due to the numerous failed clinical trials of anti-amyloid drugs, microtubule associated protein tau (MAPT) now stands out as one of the most promising targets for AD therapy. In this study, we report for the first time the structure-dependent MAPT aggregation inhibition of carbon nitride dots (CNDs). CNDs have exhibited great promise as a potential treatment of Alzheimer's disease (AD) by inhibiting the aggregation of MAPT. In order to elucidate its structure-activity relationship, CNDs were separated via column chromatography and five fractions with different structures were obtained that were characterized by multiple spectroscopy methods. The increase of surface hydrophilic functional groups is consistent with the increase of polarity from fraction 1 to 5. Particle sizes (1-2 nm) and zeta potentials (~-20 mV) are similar among five fractions. With the increase of polarity from fraction 1 to 5, their MAPT aggregation inhibition capacity was weakened. This suggests hydrophobic interactions between CNDs and MAPT, validated via molecular dynamics simulations. With a zebrafish blood-brain barrier (BBB) model, CNDs were observed to cross the BBB through passive diffusion. CNDs were also found to inhibit the generation of multiple reactive oxygen species, which is an important contributor to AD pathogenesis.

20.
J Colloid Interface Sci ; 616: 701-708, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35247808

RESUMO

This study investigates the interfacial behavior of the proteinase K enzyme at air-water interface. Adsorption of enzyme on the surface was induced using saline subphase. The surface packing and stability of the enzyme was investigated using of surface pressure-area (π-A) and surface potential-area (ΔV-A) isotherms. Proteinase K enzyme forms film at air-aqueous interface and demonstrates good stability as shown through compression-decompression cycle experiments. To characterize the surface assembly morphology of the interfacial enzymes UV-vis and fluorescence spectroscopic techniques were used. The data revealed that the enzyme Langmuir monolayer has good homogeneity with no evidence of aggregates during compression. The secondary structure of the enzyme at interface was determined to be α-helix using p-polarized infrared-reflection absorption spectroscopy. This was confirmed through Circular dichroism spectra of the enzyme Langmuir-Blodgett (LB) film which showed that the major conformation present were α-helices.


Assuntos
Água , Endopeptidase K , Estrutura Secundária de Proteína , Espectrometria de Fluorescência , Espectrofotometria Infravermelho , Propriedades de Superfície , Água/química
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