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1.
ACS Omega ; 5(31): 19796-19804, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32803075

RESUMO

Bone regeneration has attracted extensive attention in the field of regenerative medicine. The influence of biomaterial on the extracellular environment is important for regulating the biological functions of cells for tissue regeneration. Among the various influencing factors, we had previously demonstrated that the extracellular pH value in the local microenvironment during biomaterial degradation affected the balance of bone formation and resorption. However, there is a lack of techniques for conveniently detecting the pH of the extracellular environment. In light of the development of fluorescent pH-sensing probes, herein, we fabricated a novel ratiometric fluorescent microgel (F-MG) for real-time and spatiotemporal monitoring of microenvironment pH. F-MGs were prepared from polyurethane with a size of around 75 µm by loading with pH-sensitive bovine serum albumin nanoparticles (BNPs) and pH-insensitive Nile red as a reference. The pH probes exhibited reversible fluorescence response to pH change and worked in a linear range of 6-10. F-MGs were biocompatible and could be used for long-term pH detection. It could be used to map interfacial pH on biomaterials during their degradation through pseudocolored images formed by the fluorescence intensity ratio between the green fluorescence of BNPs and the red fluorescence of Nile red. This study provided a useful tool for studying the influence of biomaterial microenvironment on biological functions of surrounding cells.

2.
Dalton Trans ; 49(32): 11192-11200, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32748922

RESUMO

Photodynamic therapy (PDT) has been widely used in conjunction with molecular oxygen to cause cancer cell death. Hypoxia, the inherent property in solid tumors, is the obstacle during the process of PDT. It is urgent to develop PDT photosensitizers independent of the oxygen concentration. Herein, triphenylamine-modified Ru(ii) complexes have been used as photosensitizers to produce superoxide anions (O2-˙) and hydroxyl radicals (˙OH) through a type I photochemical process. Ru(ii) complexes with triphenylamine can provide a possibility to drive the reactive oxygen species production through low oxidation potential and good light-harvesting abilities. The investigation on light-mediated radical production showed that Ru4 could produce abundant ˙OH and O2-˙ compared to Ru1-Ru3 under hypoxic environments owing to the strong absorption. These radicals exhibit potent toxicity, which can damage the neighbouring biomolecules and cause the apoptosis of cancer cells. The PDT effect was evaluated in vitro under hypoxia, suggesting that Ru4 could maintain excellent performance in inducing a sharp decrease in the activity of cancer cells.

3.
J Mater Chem B ; 8(33): 7356-7364, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32648568

RESUMO

The preferable photoconversion tunability of conjugated polymers (CPs) is of great interest in cancer phototherapy. However, very few molecular design strategies have been developed for achieving CPs with highly efficient photoconversion performance. Herein, a rational design of near-infrared (NIR) Pt-acetylide conjugated polymer CP3 with highly efficient photoconversion behaviors for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) was demonstrated. CP3 containing boron dipyrromethene (BDP) units displayed intense absorption peaks in the NIR region, which were red-shifted approximately 60 nm compared to the corresponding small-molecule precursor of BDP. Compared with control polymers CP1 and CP2, after the introduction of Pt into CP3, the triplet state, which benefits the generation of reactive oxygen species for photodynamic therapy, was identified clearly in both CP3 and the prepared CP3 nanoparticles (CP3-NPs) by ultrafast femtosecond transient absorption (fs-TA) spectroscopy. Notably, different from the traditional nonradiative decay channel with lifetime of 1.1 ps in CP3, CP3-NPs possess an additional nonradiative decay channel with lifetime of 10 ps, both of which contribute to the superior photothermal conversion effect upon 808 nm irrradiation. All these photoconversion performances lead to excellent tumor ablation. This study elucidates the excited-state dynamics in Pt-acetylide CPs, which provide an insightful understanding and valuable guidelines for the future design of high-performance theranostic agents based on CPs for synergistic cancer phototherapy.

4.
J Chromatogr A ; 1625: 461338, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32709362

RESUMO

Until today, ion-pair reversed-phase chromatography is still the dominating method for analytical characterization of synthetic oligonucleotides. Its hyphenation with mass spectrometry, however, has some drawbacks such as ion-suppression in electrospray ionization. To overcome this problem, we present in this work a multiple heart-cutting (MHC) two-dimensional liquid chromatography (2D-LC) method with ultra-violet (UV) and electrospray ionization (ESI) mass spectrometry (MS) detection. A reversed-phase/weak anion-exchange (RP/WAX) stationary phase in the first dimension (1D) provides the selectivity for separation of structurally closely related oligonucleotide sequences and deletions (shortmers), respectively, using a mixed pH/triethylammonium phosphate buffer gradient at constant organic modifier content. Heart cuts of the oligonucleotide peaks are transferred to the second dimension (2D) via a multiple heart-cutting valve which is equipped with two loop decks. The 2D RP column is used for desalting via a diverter valve. Active solvent modulation enables to refocus the oligonucleotide peak into a sharp zone by 2D RP entirely free of non-volatile buffer components and ion-pair agents. Oligonucleotides can thus be sensitively detected by ESI-QTOF-MS under MS-compatible conditions.


Assuntos
Cromatografia de Fase Reversa/métodos , Oligonucleotídeos/química , Oligonucleotídeos/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray/métodos , Ânions , Cromatografia por Troca Iônica , Oligonucleotídeos/análise , Polímeros/química
5.
ACS Appl Mater Interfaces ; 12(18): 20180-20190, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32281784

RESUMO

The development of metallacycles with high stability and intense near-infrared (NIR) absorption is important for biomedical applications. However, very few molecular design strategies have been developed on such metallacycles. Herein, we report a new series of stable and well-defined NIR-absorbing metallacycles (M1-M3) through the Pt-acetylide coordination with highly efficient photoconversion performance for cancer phototherapy. The metallacycles showed high stability and strong NIR absorption, and the absorption peaks were red shifted approximately 30 nm in comparison with their corresponding precursors. The introduction of Pt into metallacycles promotes significant photoconversions, including the singlet-to-triplet and nonradiative transitions. Moreover, the fabricated M3 nanoparticles (M3-NPs) showed favorable photoconversions into both thermal effect and singlet oxygen generation upon NIR irradiation, achieving tumor ablation. This novel design of Pt-acetylide metallacycles possesses not only complex topological architectures but also a valuable paradigm for precise cancer phototherapy, which is important for grafting stimuli-responsive functional groups into metallacycles for the development of high-performance biomedical supramolecular materials.

6.
Nanoscale ; 12(2): 877-887, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31833519

RESUMO

Engineered exosomes have become popular drug delivery carriers for cancer treatment. This is partially due to the interesting property, i.e. exosome organotropism, which plays an important role in organ distribution post systemic administration. Here, we demonstrated that breast cancer (MDA-MB-231) cell-derived exosomes (231-Exo) could be specifically internalized by non-small cell lung cancer cells via a specific interaction between overexpressed integrin ß4 (on exosomes) and surfactant protein C (SPC) on the cancer cells. We showed that 231-Exo was capable of recognizing A549 cells in blood and effectively escaping from the immune surveillance system in vitro. Once loaded with microRNA molecules in the exosome carriers, the resulting, miRNA-126 loaded 231-Exo (miRNA-231-Exo) strongly suppressed A549 lung cancer cell proliferation and migration through the interruption of the PTEN/PI3K/AKT signaling pathway. Intravenous administration of the miRNA-126 laden exosomes led to an effective lung homing effect in mice. When tested in a lung metastasis model, miRNA-231-Exo resulted in an efficacious effect in inhibiting the formulation of lung metastasis in vivo. Collectively, our data demonstrated the possibility of using the organotropism feature of exosomes in exosome carrier design, generating a potent anti-metastasis effect in a mouse model.

7.
Int J Biol Macromol ; 143: 602-609, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31837362

RESUMO

We report the inclusion of cyclolipopeptides (CL) from Bacillus subtilis in the production of an easily removed alginate coating for the preservation of vulnerable berries. The sodium alginate-CL (SA-CL) coating films exhibited potent antifungal and freshness-maintaining properties during the storage of blueberries, the 3% CL-added film decreased total fungal count to 2.5 × 103 cfu/g at the end of the storage. The SA-CL films had poor mechanical properties (i.e., tensile strength and elongation at break), low water vapor permeability and high water solubility. The addition of CL (3%) decreased the tensile strength and elongation at break of the SA-CL film to 0.37 mPa and 2.57%, respectively, and increased the water solubility to 28.92%. But the water vapor permeability of the 3% film was lowered to 398.10 g/m2/day. These results implied the film was suitable for the coating of vulnerable berries. Further research revealed that ionic and hydrogen bonding interactions between CL and alginate stabilized the network of the coating film while the fatty acid moiety weakened the strength and crystallinity and restricted the water transfer of the coating film. Our findings provide an effective route to an easily washed alginate coating film through inclusion of amphiphilic antifungal substances.

8.
Acta Trop ; 201: 105211, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31600522

RESUMO

Enterocytozoon bieneusi is a potentially important zoonotic pathogen. However, there is no information on E. bieneusi infection of captive long-tailed macaques (Macaca fascicularis) in Hainan Province, China. Here 193 fecal specimens of M. fascicularis were collected from a breeding base in Hainan Province, China, housing non-human primates for experimental use. E. bieneusi was identified and genotyped by nested PCR analysis of the internal transcribed spacer (ITS) region of the rRNA gene. A total of 59 (30.6%) specimens were PCR-positive for E. bieneusi and 16 ITS genotypes were identified including nine known genotypes: Type IV (n = 19), D (n = 11), CM1 (n = 8), PigEBITS7 (n = 4), Pongo2 (n = 4), Peru8 (n = 3), Peru11 (n = 1), WL21 (n = 1) and CM2 (n = 1) and seven novel genotypes HNM-I to HNM-VII (one each). Importantly, genotypes D, Type IV, Peru8, PigEBITS7, and Peru11, which were the predominant (38/59, 64.4%) genotypes identified among captive M. fascicularis in this study, are also well-known human-pathogenic genotypes. All the genotypes of E. bieneusi identified here, including the seven novel ones, belonged to zoonotic Group 1. This is the first report of the identification of E. bieneusi in M. fascicularis in Hainan Province, China. The finding that the numerous known human-pathogenic types and seven novel genotypes of E. bieneusi all belong to zoonotic Group 1 indicates the possibility of transmission of this important pathogenic parasite between M. fascicularis and humans.


Assuntos
Enterocytozoon/genética , Genótipo , Macaca fascicularis/parasitologia , Microsporidiose/epidemiologia , Microsporidiose/genética , Filogenia , Zoonoses/genética , Animais , China/epidemiologia , Variação Genética , Humanos , Prevalência , Zoonoses/epidemiologia
9.
J Am Chem Soc ; 141(44): 17482-17486, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31647229

RESUMO

Photochemical reactions at lower energy than the absorption window are currently achieved by multi-photon processes, including two-photon absorption and photon upconversion, which have limited energy utilization efficiency. Here, we report a one-photon strategy based on triplet-triplet energy transfer (TTET) between a photosensitizer and a photocleavable molecule to achieve photolysis at low energy. To verify this concept, we chose platinum(II) tetraphenyltetrabenzoporphyrin (PtTPBP) as the photosensitizer and synthesized a boron-dipyrromethene (BODIPY)-based prodrug as the photocleavable molecule. Photolysis of the prodrug is achieved by TTET upon excitation of PtTPBP at 625 nm with a photolysis quantum yield of 2.8%. Another demonstration shows an unexpected higher photolysis quantum yield than the direct excitation at 530 nm. This strategy opens a new path for achieving photolysis at long wavelengths, benefiting the applications in biological studies, photopharmacology, and photoresponsive drug delivery.

10.
J Nanobiotechnology ; 17(1): 78, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31269964

RESUMO

BACKGROUND: The construction of a multifunctional drug delivery system with a variety of advantageous features, including targeted delivery, controlled release and combined therapy, is highly attractive but remains a challenge. RESULTS: In this study, we developed a MoS2-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving targeted delivery of camptothecin (CPT) and dual-stimuli-responsive drug release. HA was connected to MoS2 via a disulfide linkage, forming a sheddable HA shell on the surface of MoS2. This unique design not only effectively prevented the encapsulated CPT from randomly leaking during blood circulation but also significantly accelerated the drug release in response to tumor-associated glutathione (GSH). Moreover, the MoS2-based generated heat upon near-infrared (NIR) irradiation could further increase the drug release rate as well as induce photothermal ablation of cancer cells. The results of in vitro and in vivo experiments revealed that MoS2-SS-HA-CPT effectively suppressed cell proliferation and inhibited tumor growth in lung cancer cell-bearing mice under NIR irradiation via synergetic chemo-photothermal therapy. CONCLUSIONS: The as-prepared MoS2-SS-HA-CPT with high targeting ability, dual-stimuli-responsive drug release, and synergistic chemo-photothermal therapy may provide a new strategy for cancer therapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Dissulfetos/química , Portadores de Fármacos/química , Molibdênio/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Feminino , Corantes Fluorescentes/química , Humanos , Ácido Hialurônico/química , Hipertermia Induzida , Raios Infravermelhos , Camundongos Nus , Transplante de Neoplasias , Oxirredução , Fotoquimioterapia/métodos
11.
ChemMedChem ; 14(15): 1378-1383, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31210412

RESUMO

The development of efficient phototherapeutic agents (PTA) through rational and specific principles exhibits great potential to the biomedical field. In this study, a facile and rational strategy was used to design PTA through perturbation theory. According to the theory, both the intersystem crossing rate for singlet oxygen generation and nonradiative transition for photothermal conversion efficiency can be simultaneously enhanced by the rational optimization of donor-acceptor groups, heavy atom number, and their functional positions, which can effectively decrease the energy gap between the singlet and triplet states and increase the spin-orbit coupling constant. Finally, efficient PTA were obtained that showed excellent performance in multimode-imaging-guided synergetic photodynamic/photothermal therapy. This study therefore expands the intrinsic mechanism of organic PTA and should help guide the rational design of future organic PTA via perturbation theory.

12.
Free Radic Biol Med ; 129: 107-115, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30227269

RESUMO

S-nitrosocaptopril (CapNO) possesses dual capacities of both Captopril and an NO donor with enhanced efficacy and reduced side effects. CapNO crystals are difficult to make due to its unstable S-NO bond. Here, we report a novel stable S-nitrosocaptopril monohydrate (CapNO·H2O) that is stabilized by intermolecular five-membered structure, where one H of H2O forms a hydrogen bond with O- of the stable resonance zwitterion Cap-S+=N-O-, and the O in H2O forms the dipole-dipole interaction with S+ through two unpaired electrons. With the chelation and common ion effect, we synthesized and characterized CapNO·H2O that is stable at 4 °C for 180 days and thereafter without significant degradation. Compared to Captopril, CapNO showed direct vasorelaxation and beneficial effect on PAH rats, and could be self-assembled in rat stomach when Captopril and NaNO2 were given separately. This novel CapNO·H2O with low entropy paves an avenue for its clinical trials and commercialization.


Assuntos
Anti-Hipertensivos/farmacologia , Captopril/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Doadores de Óxido Nítrico/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/síntese química , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiopatologia , Captopril/administração & dosagem , Captopril/síntese química , Captopril/química , Captopril/metabolismo , Captopril/farmacologia , Cristalização , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Masculino , Doadores de Óxido Nítrico/síntese química , Ratos , Ratos Sprague-Dawley , Nitrito de Sódio/administração & dosagem , Nitrito de Sódio/química , Nitrito de Sódio/metabolismo , Estômago/química , Técnicas de Cultura de Tecidos , Resistência Vascular/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/síntese química
13.
Biochim Biophys Acta ; 1858(8): 1801-11, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27117641

RESUMO

The clathrin-mediated endocytosis is likely a major mechanism of liposomes' internalization. A kinetic approach was used to assess the internalization mechanism of doxorubicin (Dox) loaded cationic liposomes and to establish physiology-based cell membrane traffic mathematic models. Lipid rafts-mediated endocytosis, including dynamin-dependent or -independent endocytosis of noncaveolar structure, was a dominant process. The mathematic models divided Dox loaded liposomes binding lipid rafts (B) into saturable binding (SB) and nonsaturable binding (NSB) followed by energy-driven endocytosis. The intracellular trafficking demonstrated early endosome-late endosome-lysosome or early/late endosome-cytoplasm-nucleus pathways. The three properties of liposome structures, i.e., cationic lipid, fusogenic lipid, and pegylation, were investigated to compare their contributions to cell membrane and intracellular traffic. The results revealed great contribution of cationic lipid DOTAP and fusogenic lipid DOPE to cell membrane binding and internalization. The valid Dox in the nuclei of HepG2 and A375 cells treated with cationic liposomes containing 40mol% of DOPE were 1.2-fold and 1.5-fold higher than that in the nuclei of HepG2 and A375 cells treated with liposomes containing 20mol% of DOPE, respectively, suggesting the dependence of cell type. This tendency was proportional to the increase of cell-associated total liposomal Dox. The mathematic models would be useful to predict intracellular trafficking of liposomal Dox.


Assuntos
Doxorrubicina/análogos & derivados , Endocitose/fisiologia , Microdomínios da Membrana/fisiologia , Modelos Biológicos , Transporte Biológico , Cátions , Linhagem Celular , Doxorrubicina/administração & dosagem , Doxorrubicina/metabolismo , Ácidos Graxos Monoinsaturados/química , Células Hep G2 , Humanos , Lipossomos , Fusão de Membrana , Lipídeos de Membrana/química , Microscopia de Fluorescência , Fosfatidiletanolaminas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Compostos de Amônio Quaternário/química
14.
Tumour Biol ; 35(7): 7217-23, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24771263

RESUMO

Numerous attempts for detection of circulating tumor cells (CTC) have been made to develop reliable assays for early diagnosis of cancers. In this study, we validated the application of folate receptor α (FRα) as the tumor marker to detect CTC through tumor-specific ligand PCR (LT-PCR) and assessed its utility for diagnosis of bladder transitional cell carcinoma (TCC). Immunohistochemistry for FRα was performed on ten bladder TCC tissues. Enzyme-linked immunosorbent assay (ELISA) for FRα was performed on both urine and serum specimens from bladder TCC patients (n = 64 and n = 20, respectively) and healthy volunteers (n = 20 and n = 23, respectively). Western blot analysis and qRT-PCR were performed to confirm the expression of FRα in bladder TCC cells. CTC values in 3-mL peripheral blood were measured in 57 bladder TCC patients, 48 healthy volunteers, and 15 subjects with benign urologic pathologies by the folate receptor α ligand-targeted PCR. We found that FRα protein was overexpressed in both bladder TCC cells and tissues. The levels of FRα mRNA were also much higher in bladder cancer cell lines 5637 and SW780 than those of leukocyte. Values of FRα were higher in both serum and urine specimens of bladder TCC patients than those of control. CTC values were also higher in 3-mL peripheral blood of bladder TCC patients than those of control (median 26.5 Cu/3 mL vs 14.0 Cu/3 mL). Area under the receiver operating characteristic (ROC) curve for bladder TCC detection was 0.819, 95 % CI (0.738-0.883). At the cutoff value of 15.43 Cu/3 mL, the sensitivity and the specificity for detecting bladder cancer are 82.14 and 61.9 %, respectively. We concluded that quantitation of CTCs through FRα ligand-PCR could be a promising method for noninvasive diagnosis of bladder TCC.


Assuntos
Carcinoma de Células de Transição/sangue , Receptor 1 de Folato/sangue , Células Neoplásicas Circulantes , Neoplasias da Bexiga Urinária/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Receptor 1 de Folato/isolamento & purificação , Humanos , Ligantes , Masculino , RNA Mensageiro/biossíntese , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/patologia
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