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In this work, we introduced the acrylate recognition group into dicyanoisophorone derivative DCI-C-OH to construct the NIR fluorescent probe DCI-C-Cys with a large Stokes shift (240 nm). DCI-C-Cys could specifically respond to Cys, resulting in a 22-fold increase in fluorescence intensity at 702 nm. Meanwhile, the probe has the advantages of good water solubility, high sensitivity (93 nM), and excellent biocompatibility. Moreover, DCI-C-Cys successfully monitored endogenous and exogenous Cys in HepG2 cells and zebrafish. Most importantly, we found that balsam pear polysaccharide could lead to the increase of intracellular Cys levels, which might be conducive to the further study of the antioxidant mechanism of balsam pear polysaccharide.
Assuntos
Corantes Fluorescentes , Pyrus , Animais , Bálsamos , Cisteína/metabolismo , Células HeLa , Humanos , Limite de Detecção , Polissacarídeos/farmacologia , Regulação para Cima , Peixe-Zebra/metabolismoRESUMO
Cardamonin (CD), a naturally occurring chalcone isolated from large black cardamom, was previously reported to suppress the proliferation of breast cancer cells. However, its precise molecular anti-tumor mechanisms have not been well elucidated. In this study, we found that CD markedly inhibited the proliferation of MDA-MB 231 and MCF-7 breast cancer cells through the induction of G2/M arrest and apoptosis. Reactive oxygen species (ROS) plays a pivotal role in the inhibition of CD-induced cell proliferation. Treatment with N-acetyl-cysteine (NAC), an ROS scavenger, blocked CD-induced G2/M arrest and apoptosis in this study. Quenching of ROS by overexpression of catalase also blocked CD-induced cell cycle arrest and apoptosis. We showed that CD enhanced the expression and nuclear translocation of Forkhead box O3 (FOXO3a) via upstream c-Jun N-terminal kinase, inducing the expression of FOXO3a and its target genes, including p21, p27, and Bim. This process led to the reduction of cyclin D1 and enhancement of activated caspase-3 expression. The addition of NAC markedly reversed these effects, knockdown of FOXO3a using small interfering RNA also decreased CD-induced G2/M arrest and apoptosis. In vivo, CD efficiently suppressed the growth of MDA-MB 231 breast cancer xenograft tumors. Taken together, our data provide a molecular mechanistic rationale for CD-induced cell cycle arrest and apoptosis in breast cancer cells.
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Carbon monoxide (CO) gas therapy has shown great potential as a very promising approach in the ongoing fight against tumors. However, delivering unstable CO to the tumor site and safely releasing it for maximum efficacy still have unsatisfactory outcomes. In this study, we've developed nanotheranostics (IN-DPPCO NPs) based on conjugated polymer IN-DPP and carbon monoxide (CO) carrier polymer mPEG(CO) for photothermal augmented gas therapy. The IN-DPPCO NPs can release CO with the hydrogen peroxide (H2O2) overexpressed in the tumor microenvironment. Meanwhile, IN-DPPCO NPs exhibit strong absorption in the near-infrared window, showing a high photothermal conversion efficiency of up to 41.5% under 808 nm laser irradiation. In vitro and in vivo experiments demonstrate that these nanotheranostics exhibit good biocompatibility. Furthermore, the synergistic CO/photothermal therapy shows enhanced therapeutic efficacy compared to gas therapy alone. This work highlights the great promise of conjugated polymer nanoparticles as versatile nanocarriers for spatiotemporally controlled and on-demand delivery of gaseous messengers to achieve precision cancer theranostics.
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Peróxido de Hidrogênio , Neoplasias , Humanos , Monóxido de Carbono , Fototerapia , Neoplasias/terapia , Polímeros , Microambiente TumoralRESUMO
Photothermal therapy (PTT) has received constant attention as a promising cancer treatment. However, PTT-induced inflammation can limit its effectiveness. To address this shortcoming, we developed second near-infrared (NIR-II) light-activated nanotheranostics (CPNPBs), which include a thermosensitive nitric oxide (NO) donor (BNN6) to enhance PTT. Under a 1064 nm laser irradiation, the conjugated polymer in CPNPBs serves as a photothermal agent for photothermal conversion, and the generated heat triggers the decomposition of BNN6 to release NO. The combination of hyperthermia and NO generation under single NIR-II laser irradiation allows enhanced thermal ablation of tumors. Consequently, CPNPBs can be exploited as potential candidates for NO-enhanced PTT, holding great promise for their clinical translational development.
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Nanopartículas , Terapia Fototérmica , Fototerapia , Óxido Nítrico , Nanomedicina Teranóstica , Polímeros , Linhagem Celular TumoralRESUMO
To date, photoacoustic imaging (PAI) and PAI-guided photothermal therapy (PTT) have been performed for noninvasive cancer diagnosis and precise ablation of tumors. To conduct concurrent PAI and PTT, it is essential to develop theranostic agents with strong optical absorption and high photothermal transfer efficiency. In this study, we have engineered theranostic agents with tunable absorptions based on conjugated polymer dots (Pdots) with different structures via the simple precipitation method. The as-synthesized Pdots exhibit strong absorption, high biocompatibility, and superior stability. In addition, the Pdots demonstrate that they can serve as contrast agents for multiscale PAI in vitro and in vivo. More importantly, a high photothermal conversion efficiency up to 40% is reached under irradiation with LED light, resulting in effective cancer treatment with extremely low light dose. Consequently, they show the potential as imaging-guided therapeutic agents for clinical cancer treatment and various biomedical applications.
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Materiais Biocompatíveis/farmacologia , Neoplasias da Mama/tratamento farmacológico , Meios de Contraste/farmacologia , Fototerapia , Polímeros/farmacologia , Tiofenos/farmacologia , Engenharia Tecidual , Absorção Fisiológica/efeitos dos fármacos , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/síntese química , Meios de Contraste/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células MCF-7 , Estrutura Molecular , Técnicas Fotoacústicas , Polímeros/síntese química , Polímeros/química , Relação Estrutura-Atividade , Nanomedicina Teranóstica , Tiofenos/químicaRESUMO
BACKGROUND: The effectiveness of meditative movement (tai chi, yoga, and qigong) on COPD remained unclear. We undertook a systematic review and meta-analysis to determine the effectiveness of meditative movement on COPD patients. METHODS: We searched PubMed, Web of Science, EMBASE, and the Cochrane Center Register of Controlled Trials for relevant studies. The methods of standard meta-analysis were utilized for identifying relevant researches (until August 2017), quality appraisal, and synthesis. The primary outcomes were the 6-minute walking distance (6MWD), lung function, and dyspnea levels. RESULTS: Sixteen studies involving 1,176 COPD patients were included. When comparing with the control group, the 6MWD was significantly enhanced in the treatment group (3 months: mean difference [MD]=25.40 m, 95% CI: 16.25 to 34.54; 6 months: MD=35.75 m, 95% CI: 22.23 to 49.27), as well as functions on forced expiratory volume in 1 s (FEV1) (3 months: MD=0.1L, 95% CI: 0.02 to 0.18; 6 months: MD=0.18L, 95% CI: 0.1 to 0.26), and FEV1 % predicted (3 months: 4L, 95% CI: 2.7 to 5.31; 6 months: MD=4.8L, 95% CI: 2.56 to 7.07). Quality of life for the group doing meditative movement was better than the control group based on the Chronic Respiratory Disease Questionnaire dyspnea score (MD=0.9 units, 95% CI: 0.51 to 1.29) and fatigue score (MD=0.75 units, 95% CI: 0.42 to 1.09) and the total score (MD=1.92 units, 95% CI: 0.54 to 3.31). CONCLUSION: Meditative movement may have the potential to enhance lung function and physical activity in COPD patients. More large-scale, well-designed, multicenter, randomized controlled trials should be launched to evaluate the long-range effects of meditative movement.
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Técnicas de Exercício e de Movimento , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Técnicas de Exercício e de Movimento/efeitos adversos , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qigong , Qualidade de Vida , Recuperação de Função Fisiológica , Testes de Função Respiratória , Inquéritos e Questionários , Tai Chi Chuan , Resultado do Tratamento , Teste de Caminhada , YogaRESUMO
Theranostic nanomedicines involved in photothermal therapy (PTT) have received constant attention as promising alternatives to traditional therapies in clinic. However, most photothermal agents are limited by their instability and low photothermal conversion efficiency. In this study, we report new conjugated polymer dots (Pdots) as multifunctional agents for photoacoustic (PA) imaging-guided PTT. The novel 4,8-bis[5-(2-ethylhexyl)thiophen-2-yl]-2,6-bis(trimethylstannyl)benzo[1,2-b:4,5-b']dithiophene-6,6'-dibromo-N,N'-(2-ethylhexyl)isoindigo (BDT-IID) Pdots are readily fabricated though nanoreprecipitation and can absorb strongly in the 650-700 nm region. Furthermore, the BDT-IID Pdots possess a stable nanostructure and an extremely low biotoxicity. In particular, its photothermal conversion efficiency can be up to 45%. More importantly, our in vivo results exhibit that the BDT-IID Pdots are able to offer concurrently enhanced PA contrast and sufficient photothermal effect. Consequently, the BDT-IID Pdots can be exploited as a unique theranostic nanoplatform for PA imaging-guided PTT of tumors, holding great promise for their clinical translational development.
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Técnicas Fotoacústicas , Nanopartículas , Fototerapia , Polímeros , Nanomedicina TeranósticaRESUMO
In this study, we firstly describe the synthesis and characterization of amphiphilic carbonaceous particles (ACPs) derived from Escherichia coli (E. coli) cells. These ACPs possess a versatile functional surface and are highly dispersible in solvents of different polarities, which enable them to serve as a motif for functional groups. Secondly, we describe the construction of a multifunctional antifouling polymer surface based on amphiphilic carbonaceous conjugates of Trypsin (Tryp) and vancomycin hydrochloride (Van). The use of ACPs not only achieves the uniform incorporation of Tryp and Van into a hydrophobic polymer matrix, but also retains their activity and stability. The resultant hybrid film possesses strong proteolytic and bactericidal activities and displays a strong ability in preventing the attachment of human serum albumin/human fibrinogen and S. aureus by the contact-mediated protein-degrading and bacteria-killing mechanism. Further investigations of stability and reusability indicate that the hybrid film is highly active and stable under physiological conditions. The strategy described herein for the construction of multifunctional antifouling surfaces is simple and thus can be extended to other functional molecules and matrices for broader antifouling applications.