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1.
Macromol Rapid Commun ; 44(19): e2300282, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37461805

RESUMO

Achieving high-performance luminescence for underwater bonding remains a significant challenge in materials science. This study addresses this issue by synthesizing a luminescent material based on an aggregation-induced emission (AIE) monomer and copolymerizing it with lipoic acid (LA) to create an AIE supramolecular polymer. The resulting copolymer exhibits strong fluorescence under ultraviolet (UV) irradiation at 365 nm due to the AIE of TPEE and enables underwater adhesion. The P(LA-TPEE) polymer demonstrates potential for digital encryption and decryption of quick response (QR) codes underwater. Furthermore, it can dissolve well in anhydrous ethanol, producing an environment-friendly and super waterproof adhesive. Most notably, the P(LA-TPEE) solution can be sprayed on human skin, creating an invisible tattoo that only became visible under UV light due to the hydrogen bond (H-bond) and π-π structures. This smart tattoo can be quickly wiped away with alcohol, avoiding the painful and harmful process of tattoo removal. It can also be repeatedly applied to draw the preferred tattoo pattern. This AIE supramolecular polymer shows great potential in underwater adhesion and repair, underwater message encryption, and non-toxic and painless invisible tattooing. Overall, this study provides a valuable approach for material design in the future.


Assuntos
Tatuagem , Humanos , Corantes , Pele , Adesivos , Polímeros/química
2.
Molecules ; 26(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33808961

RESUMO

Aromatic volatile compounds are important contributors to fruit quality that vary among different cultivars. Herein, headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry was used to determine changes in volatile compounds and related gene expression patterns in "Ruixue" and "Fuji" apples (Malus domestica Borkh.) during fruit development and maturation. Volatile compounds detected in the fruit of both cultivars exhibited similar trends across different developmental stages. In the early stages of "Ruixue" fruit development (60 days after full bloom), there were fewer volatile compounds, mainly aldehydes (87.0%). During fruit maturation (180 days after full bloom), the types and amounts of volatile compounds increased, mainly including esters (37.6%), and alkenes (23.2%). The total volatile concentration, the types of major volatile compounds, and their relative content in both cultivars varied across different stages. Gene expression analysis indicated that the upregulation of MdLOX, MdAAT2, and MdADH3 was associated with increased aroma compound content, especially esters, during fruit development in both cultivars. Changes in the expression of MdArAT, MdACPD, MdADH3, MdAAT2, and MdLOX may lead to differences in volatile compounds between apple cultivars.


Assuntos
Genes de Plantas , Malus/química , Malus/genética , Compostos Orgânicos Voláteis/análise , Frutas/química , Frutas/genética , Frutas/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Concentração de Íons de Hidrogênio , Malus/crescimento & desenvolvimento , Odorantes/análise , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Especificidade da Espécie , Açúcares/análise , Compostos Orgânicos Voláteis/química
3.
Angew Chem Int Ed Engl ; 60(12): 6509-6517, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33427367

RESUMO

Cancer chemotherapy typically relies on drug endocytosis and inhibits tumor cell proliferation via intracellular pathways; however, severe side effects may arise. In this study, we performed a first attempt to develop macromolecular-induced extracellular chemotherapy involving biomineralization by absorbing calcium from the blood through a new type of drug, polysialic acid conjugated with folate (folate-polySia), which selectively induces biogenic mineral formation on tumor cells and results in the pathological calcification of tumors. The macromolecule-initiated extracellular calcification causes cancer cell death mainly by intervening with the glycolysis process in cancer cells. Systemic administration of folate-polySia inhibited cervical and breast tumor growth and dramatically improved survival rates in mice. This study provides an extracellular therapeutic approach for malignant tumor diseases via calcification that is ready for clinical trials and offers new insights into macromolecular anticancer drug discovery.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ácido Fólico/farmacologia , Substâncias Macromoleculares/farmacologia , Ácidos Siálicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/química , Humanos , Substâncias Macromoleculares/administração & dosagem , Substâncias Macromoleculares/química , Estrutura Molecular , Ácidos Siálicos/administração & dosagem , Ácidos Siálicos/química , Relação Estrutura-Atividade
4.
Int J Mol Sci ; 20(9)2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083412

RESUMO

Apple (Malus × domestica Borkh.) is one of the most important cultivated tree fruit crops worldwide. However, sustainable apple production is threatened by powdery mildew (PM) disease, which is caused by the obligate biotrophic fungus Podosphaera leucotricha. To gain insight into the molecular basis of the PM infection and disease progression, RNA-based transcriptional profiling (RNA-seq) was used to identify differentially expressed genes (DEGs) in apples following inoculation with P. leucotricha. Four RNA-seq libraries were constructed comprising a total of 214 Gb of high-quality sequence. 1177 DEGs (661 upregulated and 629 downregulated) have been identified according to the criteria of a ratio of infection/control fold change > 2, and a false discovery rate (FDR) < 0.001. The majority of DEGs (815) were detected 12 h after inoculation, suggesting that this is an important time point in the response of the PM infection. Gene annotation analysis revealed that DEGs were predominately associated with biological processes, phenylpropanoid biosynthesis, hormone signal transduction and plant-pathogen interactions. Genes activated by infection corresponded to transcription factors (e.g., AP2/ERF, MYB, WRKY and NAC) and synthesis of defense-related metabolites, including pathogenesis-related genes, glucosidase and dehydrin. Overall, the information obtained in this study enriches the resources available for research into the molecular-genetic mechanisms of the apple/powdery mildew interactions, and provides a theoretical basis for the development of new apple varieties with resistance to PM.


Assuntos
Ascomicetos/fisiologia , Perfilação da Expressão Gênica , Malus/genética , Malus/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Folhas de Planta/genética , Folhas de Planta/microbiologia , Clorofila/metabolismo , Regulação da Expressão Gênica de Plantas , Interações Hospedeiro-Patógeno , Malondialdeído/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Transdução de Sinais/genética , Fatores de Tempo , Fatores de Transcrição/metabolismo
5.
ACS Appl Mater Interfaces ; 11(7): 7357-7368, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30682240

RESUMO

This study aimed to develop an efficient step-by-step osteosarcoma (OS)-targeting liposome system functionalized with a redox-cleavable, bone- and cluster of differentiation 44 (CD44)-dual-targeting polymer. Furthermore, the effect of coadministration of a tumor-penetrating peptide, internalizing RGD (iRGD), was investigated. First, a bone-targeting moiety, alendronate (ALN), was conjugated with hyaluronic acid (HA), a ligand for CD44. This ALN-HA conjugate was coupled with DSPE-PEG2000-COOH through a bioreducible disulfide linker (-SS-) to obtain a functionalized lipid, ALN-HA-SS-L, to be postinserted into preformed liposomes loaded with doxorubicin (DOX). The roles of ALN, HA, and the redox sensitivity of the ALN-HA-SS-L liposomes (ALN-HA-SS-L-L) in the anti-OS effect were critically evaluated against various reference liposomal formulations (with only ALN, HA, or redox sensitivity). ALN-HA-SS-L-L displayed a zeta potential of -26.07 ± 0.32 mV and selectively disassembled in the presence of a reducing agent, 10 mM glutathione, which can be found in cancer cells. Compared to various reference liposomes, ALN-HA-SS-L-L/DOX had significantly higher cytotoxicity to human OS MG-63 cells alongside high and rapid cellular uptake. In the orthotopic OS nude mouse models, ALN-HA-SS-L-L/DOX showed remarkable tumor growth suppression and prolonged survival time. This result was further improved by the coadministration of iRGD. The antitumor effects of various liposomes were ranked in the same order as the degree of tumor biodistribution shown by in vivo/ex vivo imaging: ALN-HA-SS-L-L coadministered with iRGD > ALN-HA-SS-L-L > HA-SS-L-L > HA-L-L > PEG-L> free drug. ALN-HA-SS-L-L/DOX also reduced the cardiotoxicity of DOX and lung metastases. Overall, this study demonstrated that ALN-HA-SS-L-L/DOX, equipped with bone- and CD44-dual-targeting abilities and redox sensitivity, could be a promising OS-targeted therapy. The efficacy could also be augmented by coadministration of iRGD.


Assuntos
Alendronato , Neoplasias Ósseas , Receptores de Hialuronatos/metabolismo , Proteínas de Neoplasias/metabolismo , Osteossarcoma , Alendronato/química , Alendronato/farmacocinética , Alendronato/farmacologia , Animais , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Lipossomos , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Drug Deliv ; 25(1): 900-908, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29644882

RESUMO

An estrogen (ES)-functionalized cationic liposomal system was developed and exploited for targeted delivery to osteosarcoma. Natural biocompatible chotooligosaccharides (COS, MW2-5 KDa) were covalently tethered to the liposomal surface through a disulfate bond (-SS-) to confer reduction-responsive COS detachment, whereas estrogen was grafted via polyethylene glycol (PEG 2 K) chain to achieve estrogen receptor-targeting. The liposomal carriers were prepared by the ethanol injection method and fluorescent anticancer drug doxorubicin (DOX) was loaded with ammonium sulfate gradient. The physicochemical properties, reduction-sensitivity, and the roles of estrogen on cellular uptake and tumor-targeting were studied. The Chol-SS-COS/ES/DOX liposomes were spherical with an average size about 110 nm, and high encapsulation efficiency. The liposomes were stable in physiological condition but rapidly release the payload in response to tumoral intracellular glutathione (20 mM). MTT cytotoxicity assay confirmed that Chol-SS-COS/ES/DOX liposomes exhibited higher cytotoxicity to MG63 osteosarcoma cells than to liver cells (LO2). Flow cytometry (FCM) and confocal laser scanning microscopy revealed that cellular uptake of Chol-SS-COS/ES/DOX liposomes by MG63, than the free DOX or Chol-SS-COS/DOX. Ex vivo fluorescence distribution study showed that the multifunctional liposomes selectively accumulated in the MG63 xenografts versus the organs. Chol-SS-COS/ES/DOX liposomes strongly inhibited the tumor growth and enhanced the animal survival rate. Overall, the COS grafted estrogen-functionalized cationic liposomes, fortified with glutathione-responsiveness, showed great potential for specific intracellular drug delivery to estrogen receptor-expressing tumors such as osteosarcoma.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Quitina/análogos & derivados , Colesterol/química , Doxorrubicina/administração & dosagem , Estrona/metabolismo , Glutationa/metabolismo , Osteossarcoma/tratamento farmacológico , Receptores de Estrogênio/metabolismo , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Quitina/química , Quitosana , Doxorrubicina/química , Doxorrubicina/metabolismo , Composição de Medicamentos , Liberação Controlada de Fármacos , Estrona/química , Humanos , Injeções Intravenosas , Lipossomos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligossacarídeos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Tamanho da Partícula , Polietilenoglicóis/química , Tecnologia Farmacêutica/métodos , Fatores de Tempo , Distribuição Tecidual , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Pharm Res ; 34(10): 2172-2184, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28726003

RESUMO

PURPOSE: To investigate the potential of a reduction-sensitive and fusogenic liposomes, enabled by surface-coating with chotooligosaccharides (COS) via a disulfide linker, for tumor-targeted cytoplasmic drug delivery. METHODS: COS (MW2000-5000) were chemically tethered onto the liposomes through a disulfide linker (-SS-) to cholesterol (Chol). Doxorubicin (DOX) was actively loaded in the liposomes. Their reduction-sensitivities, cellular uptake, cytotoxicity, pharmacokinetics and antitumor efficacy were investigated. RESULTS: The Chol-SS-COS/DOX liposomes (100 nm) had zeta potential of 33.9 mV and high drug loading (13% w/w). The liposomes were stable with minimal drug leakage under physiological conditions but destabilized in the presence of reducing agents, dithiothreitol (DTT) or glutathione (GSH) at 10 mM, the cytosolic level. MTT assay revealed that the cationic Chol-SS-COS/DOX liposomes had higher cytotoxicity to MG63-osteosarcoma cells than non-reduction sensitive liposome (Chol-COS/DOX). Flow cytometry and confocal microscopy revealed that Chol-SS-COS/DOX internalized more efficiently than Chol-COS/DOX with more content to cytoplasm whereas Chol-COS/DOX located around the cell membrane. Chol-SS-COS/DOX preferentially internalized into MG63 cancer cell over LO2 normal liver cells. In rats both liposomes produced a prolonged half-life of DOX by 4 - 5.5 fold (p < 0.001) compared with the DOX solution. Chol-SS-COS/DOX exhibited strong inhibitory effect on tumor growth in MG63 cell-bearing nude mice (n = 6), and extended animal survival rate. CONCLUSIONS: Reduction-responsive Chol-SS-COS liposomes may be an excellent platform for cytoplasmic delivery of anticancer drugs. Conjugation of liposomes with COS enhanced tumor cell uptake, antitumor effect and survival rate in animal models.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Quitina/análogos & derivados , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Lipossomos/química , Osteossarcoma/tratamento farmacológico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular , Quitina/química , Quitosana , Colesterol/química , Citoplasma , Doxorrubicina/química , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Nus , Oligossacarídeos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície
8.
J Control Release ; 261: 113-125, 2017 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-28666726

RESUMO

This study aimed to develop redox-sensitive and CD44-targeted liposomes to improve chemotherapy of osteosarcoma. Cationic liposomes were prepared and stabilized with a novel detachable polyethylene glycol (PEG2000) conjugated with cholesterol through a bio-reducible disulfide linker (Chol-SS-mPEG). Hyaluronic acid (HA, MW 20-40kDa), a ligand to CD44, was non-covalently coated on the cationic liposomes. Doxorubicin (DOX) was actively loaded in the liposomes as a model drug. The roles of HA and Chol-SS-mPEG on intracellular drug delivery efficiency, and antitumor efficacy were studied. The structure of Chol-SS-mPEG was confirmed with Fourier-transform infrared and nuclear magnetic resonance (1H NMR). The liposomes, Chol-SS-mPEG/HA-L had a mean diameter of 165nm, zeta potential -28.9mV, and destabilized in reducing or acidic (pH5-6) conditions. In vitro release of DOX was well-controlled at physiological conditions, but a burst release of 60% was observed in the presence of 10mM glutathione (GSH), in contrast to non-redox sensitive liposomes (Chol-mPEG/HA-L and Chol-mPEG-L). MTT cell viability assay showed that the dual-functional Chol-SS-mPEG/HA-L with a drug loading of 15.0% (w/w) had significantly higher cytotoxicity to MG63 osteosarcoma cells compared with non-reduction sensitive or non-HA coated liposomes (p<0.01), consistent with the cellular uptake and intracellular trafficking studies using confocal microscopy and flow cytometry. Furthermore, the HA-coated GSH-responsive liposomes preferentially internalized to MG63 over human liver cells LO2. In rats, liposomes stabilized with either Chol-SS-mPEG or Chol-mPEG, with or without HA, increased the half-life of DOX by >10-fold. In a MG63 xenograft mouse model, Chol-SS-mPEG/HA-L showed the most effective tumor suppression with minimal uptake by the liver compared with other liposomes. All animals treated with liposomal formulations survived, in contrast to those free-DOX treated. In conclusion, the easily prepared Chol-SS-mPEG/HA-L was demonstrated as an excellent CD44-mediated intracellular delivery system capable of long-circulation and GSH-triggered cytoplasmic drug release. Further translational and multidisciplinary research is required to make it real clinical benefits to cancer patients.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Osteossarcoma/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Citoplasma/metabolismo , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Citometria de Fluxo , Humanos , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/química , Lipossomos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Confocal , Osteossarcoma/metabolismo , Oxirredução , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley , Ensaios Antitumorais Modelo de Xenoenxerto
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