Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eur Radiol ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38265473

RESUMO

OBJECTIVE: Evaluation of tumor microvascular morphology is of great significance in tumor diagnosis, therapeutic effect prediction, and surgical planning. Recently, two-dimensional ultrasound localization microscopy (2DULM) has demonstrated its superiority in the field of microvascular imaging. However, it suffers from planar dependence and is unintuitive. We propose a novel three-dimensional ultrasound localization microscopy (3DULM) to avoid these limitations. METHODS: We investigated 3DULM based on a 2D array for tumor microvascular imaging. After intravenous injection of contrast agents, all elements of the 2D array transmit and receive signals to ensure a high and stable frame rate. Microbubble signal extraction, filtering, positioning, tracking, and other processing were used to obtain a 3D vascular map, flow velocity, and flow direction. To verify the effectiveness of 3DULM, it was validated on double helix tubes and rabbit VX2 tumors. Cisplatin was used to verify the ability of 3DULM to detect microvascular changes during tumor treatment. RESULTS: In vitro, the sizes measured by 3DULM at 3 mm and 13 mm were 178 [Formula: see text] and 182 [Formula: see text], respectively. In the rabbit tumors, we acquired 9000 volumes to reveal vessels about 30 [Formula: see text] in diameter, which surpasses the diffraction limit of ultrasound in traditional ultrasound imaging, and the results matched with micro-angiography. In addition, there were significant changes in vascular density and curvature between the treatment and control groups. CONCLUSIONS: The effectiveness of 3DULM was verified in vitro and in vivo. Hence, 3DULM may have potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease. CLINICAL RELEVANCE STATEMENT: 3D ultrasound localization microscopy is highly sensitive to microvascular changes; thus, it has clinical potential for tumor diagnosis and treatment evaluation. KEY POINTS: • 3D ultrasound localization microscopy is demonstrated on double helix tubes and rabbit VX2 tumors. • 3D ultrasound localization microscopy can reveal vessels about 30 [Formula: see text] in diameter-far smaller than traditional ultrasound. • This form of imaging has potential applications in tumor diagnosis, tumor treatment evaluation, surgical protocol guidance, and cardiovascular disease.

2.
Molecules ; 28(21)2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37959737

RESUMO

Coordination polymers (CPs) are an assorted class of coordination complexes that are gaining attention for the safe and sustainable removal of organic dyes from wastewater discharge by either adsorption or photocatalytic degradation. Herein, three different coordination polymers with compositions [Ni(HL)(H2O)2·1.9H2O] (1), [Mn3(HL)(L)(µ3-OH)(H2O)(phen)2·2H2O] (2), and [Cd(HL)4(H2O)]·H2O (3) (H3L = 2-(3,5-dicarboxyphenyl)-6-carboxybenzimidazole; phen = 1,10-phenanthroline) have been synthesized and characterized spectroscopically and by single crystal X-ray diffraction. Single crystal X-ray diffraction results indicated that 1 forms a 2D layer-like framework, while 2 exhibits a 3-connected net with the Schläfli symbol of (44.6), and 3 displays a 3D supramolecular network in which two adjacent 2D layers are held by π···π interactions. All three compounds have been used as photocatalysts to catalyze the photodegradation of antibiotic dinitrozole (DTZ) and rhodamine B (RhB). The photocatalytic results suggested that the Mn-based CP 2 exhibited better photodecomposition of DTZ (91.1%) and RhB (95.0%) than the other two CPs in the time span of 45 min. The observed photocatalytic mechanisms have been addressed using Hirshfeld surface analyses.

3.
J Bioinform Comput Biol ; 21(3): 2350011, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37325863

RESUMO

The P53 protein levels exhibit a series of pulses in response to DNA double-stranded breaks (DSBs). However, the mechanism regarding how damage strength regulates physical parameters of p53 pulses remains to be elucidated. This paper established two mathematical models translating the mechanism of p53 dynamics in response to DSBs; the two models can reproduce many results observed in the experiments. Based on the models, numerical analysis suggested that the interval between pulses increases as the damage strength decreases, and we proposed that the p53 dynamical system in response to DSBs is modulated by frequency. Next, we found that the ATM positive self-feedback can realize the system characteristic that the pulse amplitude is independent of the damage strength. In addition, the pulse interval is negatively correlated with apoptosis; the greater the damage strength, the smaller the pulse interval, the faster the p53 accumulation rate, and the cells are more susceptible to apoptosis. These findings advance our understanding of the mechanism of p53 dynamical response and give new insights for experiments to probe the dynamics of p53 signaling.


Assuntos
Reparo do DNA , Proteína Supressora de Tumor p53 , Proteína Supressora de Tumor p53/genética , Dano ao DNA , Quebras de DNA de Cadeia Dupla , Transdução de Sinais
4.
ACS Nano ; 17(7): 6410-6422, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-36988613

RESUMO

Micro-/nanorobots have attracted great interest in the field of drug delivery and treatment, while preparations for biocompatible robots are extremely challenging. Here, a self-driving yeast micro-/nanorobot (Cur@CaY-robot) is designed via dual biomineralization and acid catalysis of calcium carbonate (CaCO3). Inner nano-CaCO3 inside yeast cells (CaY) is biomineralized through cell respiration and provides nanoscaffolds for highly encapsulating curcumin (Cur). Meanwhile, the CaCO3 crystals outside yeast cells (outer-CaCO3) through uniaxial growth offer an asymmetric power source for self-propelled motility. The Cur@CaY-robot displays an efficient motion in gastric acid, with the potential for deep penetration to the thick gastric mucus, which significantly improves the accumulation of drug agents in the stomach wall tissue for robust gastritis therapy. More importantly, Ca2+ cations released from the Cur@CaY-robot also synergistically repair the gastric motility of gastritis mice. Such yeast micro-/nanorobots exhibit desirable biocompatibility and biodegradability with a good loading capacity for drugs. This work provides an idea for the design of micro-/nanorobots through an environmentally friendly biosynthesis strategy for active drug delivery and precise therapy.


Assuntos
Curcumina , Gastrite , Nanopartículas , Camundongos , Animais , Saccharomyces cerevisiae , Sistemas de Liberação de Medicamentos , Curcumina/química , Gastrite/tratamento farmacológico , Nanopartículas/química
5.
Biomaterials ; 293: 121992, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36603445

RESUMO

Sonodynamic therapy (SDT), a combination of low-intensity ultrasound with a sonosensitizer, has been explored as a promising alternative for cancer therapy. However, condensed extracellular matrix (ECM) resulting in poor perfusion and extreme hypoxia in solid tumor potentially compromises effective SDT. Herein, we develop a novel cleavable collagenase-assistant and O2-supplied nanosonosensitizer (FePO2@HC), which is embedded through fusing collagenase (CLG) and human serum albumin (HSA), followed by encapsulating Ferric protoporphyrin (FeP) and dioxygen. As a smart carrier, HSA is stimuli-responsive and collapsed by reduced glutathione (GSH) overexpressed in tumor, resulting to the release of the components in FePO2@HC. The released CLG acting as an artificial scissor, degrades the collagen fibers in tumor, thus, breaking tumor tissue and enhancing FePO2 accumulation in tumor inner with higher than that without CLG. Simultaneously, oxygen molecules are released from FePO2 in hypoxic environment and alleviate the tumor hypoxia. As a sonosensitizer, FeP is subsequently irradiated by ultrosound wave (US) and activates surrounding dioxygen to generate amount of singlet oxygen (1O2). Contributed from the ECM-degradation, such SDT-based nanosystem with increased sonosensitizer permeability and oxygen content highly improved the tumor inhibition efficacy without toxic effects. This study presents a new paradigm for ECM depletion-based strategy of deep-seated penetration, and will expand the nanomedicine application of metalloporphyrin sonosensitizers in SDT.


Assuntos
Metaloporfirinas , Nanopartículas , Neoplasias , Terapia por Ultrassom , Humanos , Neoplasias/terapia , Neoplasias/patologia , Oxigênio/metabolismo , Colagenases , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio
6.
ACS Nano ; 17(1): 421-436, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36573683

RESUMO

Glioblastoma (GBM) is the most devastating brain tumor and highly resistant to conventional chemotherapy. Herein, we introduce biomimetic nanosonosensitizer systems (MDNPs) combined with noninvasive ultrasound (US) actuation for orthotopic GBM-targeted delivery and sonodynamic-enhanced chemotherapy. MDNPs were fabricated with biodegradable and pH-sensitive polyglutamic acid (PGA) and the chemotherapeutic agent and sonosensitizer doxorubicin (DOX), camouflaged with human GBM U87 cell membranes. MDNPs presented homologous targeting accumulation and in vivo long-term circulation ability. They effectively passed through the blood-brain barrier (BBB) under US assistance and reached the orthotopic GBM site. MDNPs exhibited controllable US-elicited sonodynamic effect by generation of reactive oxygen species (ROS). ROS not only induced cancer cell apoptosis but also downregulated drug-resistance-related factors to disrupt chemoresistance and increase sensitivity to chemotherapy. The in vivo study of orthotopic GBM treatments further proved that MDNPs exhibited US-augmented synergistic antitumor efficacy and strongly prolonged the survival rate of mice. The use of low-dose DOX and the safety of US enabled repeated treatment (4 times) without obvious cardiotoxicity. This effective and safe US-enhanced chemotherapy strategy with the advantages of noninvasive brain delivery and high drug sensitivity holds great promise for deep-seated and drug-resistant tumors.


Assuntos
Glioblastoma , Nanopartículas , Humanos , Camundongos , Animais , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Biomimética , Ultrassonografia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistência a Medicamentos , Linhagem Celular Tumoral
7.
Nanomaterials (Basel) ; 12(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35055229

RESUMO

Sonodynamic therapy (SDT), as a novel cancer therapy strategy, might be a promising approach due to the depth-penetration property in tissue. Sonosensitizers are the key element for efficient SDT. However, the development of sonosensitizers with strong sonosensitization efficacy is still a significant challenge. Herein, an urchin-shaped copper-based metalloporphyrin liposome nanosystem (FA-L-CuPP) is constructed and identified as an excellent sonosensitizer. Under ultrasound (US) irradiation, FA-L-CuPP can be highly excited to generate several reactive oxygen species (ROS), such as singlet oxygen (1O2) and free radicals (⋅OH). The molecular orbital distribution calculations reveal that a strong intramolecular charge transfer might occur in the CuPP complex under US irradiation, which could afford enough energy to the surrounding O2 and H2O to concert 1O2, O2- and ⋅OH. Working as "ammunitions", the largely produced ROS can kill 4T1 tumor cells, effectively inhibiting tumor growth. This work provides an urchin-shaped nanosonosensitizer based on a copper complex, which might provide an idea to design a novel sonosensitizer for noninvasive and precise SDT antitumor applications.

8.
Biomaterials ; 281: 121341, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34995901

RESUMO

Although chimeric antigen receptor T (CAR T) cell immunotherapy has demonstrated remarkable success in clinical, therapeutic effects are still limited in solid tumor due to lack of activated T cell infiltration in immunosuppression of tumor microenvironment. Herein, we develop IL-12 nanostimulant-engineered CAR T cell (INS-CAR T) biohybrids for boosting antitumor immunity of CAR T cells via immunofeedback. As stimulating nanochaperone, IL-12-loaded human serum albumin (HSA) nanoparticles are effectively conjugated onto CAR T cells via bioorthogonal chemistry without influencing their antitumor capabilities. IL-12 is responsively released from INS-CAR T biohybrids in presence of the increased thiol groups on cell-surface triggered by tumor antigens. In return, released IL-12 obviously promotes the secretion of CCL5, CCL2 and CXCL10, which further selectively recruits and expands CD8+ CAR T cells in tumors. Ultimately, the immune-enhancing effects of IL-12 nanochaperone significantly boost CAR T cell antitumor capabilities, dramatically eliminated solid tumor and minimized unwanted side effects. Hence, immunofeedback INS-CAR T biohybrids, which include INS that serves as an intelligent 'nanochaperone', could provide a powerful tool for efficient and safe antitumor immunotherapy.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia , Imunoterapia Adotiva , Interleucina-12 , Neoplasias/terapia , Linfócitos T , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Small ; 18(12): e2104643, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34908239

RESUMO

Natural bacteria are interesting subjects for cancer treatments owing to their unique autonomy-driven and hypoxic target properties. Genetically modified bacteria (such as bacteria with msbB gene and aroA gene modifications) can effectively cross sophisticated physiological barriers and transport antitumor agents into deep tumor tissues, and they have good biosafety. Additionally, bacteria can secrete cytokines (such as interleukin-224, interferon-gamma [IFN-γ], and interleukin-1ß) and activate antitumor immune responses in the tumor microenvironment, resulting in tumor inhibition. All of these characteristics can be easily utilized to develop synergistic antitumor strategies by combining bacteria-based agents with other therapeutic approaches. Herein, representative studies of bacteria-instructed multimodal synergistic cancer therapy are introduced (e.g., photothermal therapy, chemoimmunotherapy, photodynamic therapy, and photocontrolled bacterial metabolite therapy), and their key advantages are systematically expounded. The current challenges and future prospects in advancing the development of bacteria-based micro/nanomedicines in the field of synthetic biology research are also emphasized, which will hopefully promote the development of related bacteria-based cancer therapies.


Assuntos
Nanopartículas , Neoplasias , Bactérias , Biônica , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , Microambiente Tumoral
10.
Biomater Sci ; 10(1): 294-305, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34854851

RESUMO

Sonodynamic therapy (SDT) is a highly attractive therapy due to its advantages of being non-invasive and having good penetration depth, but tumor hypoxia extremely restricts its therapeutic effect. Here, a novel oxygen-enhanced hybrid protein nanosonosensitizer system (MnPcS@HPO) is designed using human serum albumin (HSA) and hemoglobin (Hb) through disulfide reconfiguration, followed by encapsulating Mn-phthalocyanine (MnPcS), aiming to develop O2 self-supplementing nanoparticles (NPs) for enhanced SDT. Benefitting from the O2-carrying ability of Hb and the tumor-targeting property of HSA, the MnPcS@HPO NPs are able to target tumor sites and alleviate hypoxia. Meanwhile, as a sonosensitizer, MnPcS is excited under US irradiation and activates dioxygen to generate abundant singlet oxygen (1O2), resulting in oxidative damage of tumor cells. Guided by photoacoustic and magnetic resonance dual-modal imaging, the MnPcS@HPO NPs alleviate tumor hypoxia and achieve good SDT efficiency for suppressing tumor growth. This work presents a novel insight into enhanced SDT antitumor activity through natural protein-mediated tumor microenvironment improvement.


Assuntos
Nanopartículas , Terapia por Ultrassom , Linhagem Celular Tumoral , Humanos , Hipóxia , Oxigênio
11.
Adv Mater ; 33(50): e2100241, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34121236

RESUMO

Numerous clinical trials for cancer precision medicine research are limited due to the drug resistance, side effects, and low efficacy. Unsatisfactory outcomes are often caused by complex physiologic barriers and abnormal immune events in tumors, such as tumor target alterations and immunosuppression. Cell/bacteria-derived materials with unique bioactive properties have emerged as attractive tools for personalized therapy in cancer. Naturally derived bioactive materials, such as cell and bacterial therapeutic agents with native tropism or good biocompatibility, can precisely target tumors and effectively modulate immune microenvironments to inhibit tumors. Here, the recent advances in the development of cell/bacteria-based bioactive materials for immune modulation and precision therapy in cancer are summarized. Cell/bacterial constituents, including cell membranes, bacterial vesicles, and other active substances have inherited their unique targeting properties and antitumor capabilities. Strategies for engineering living cell/bacteria to overcome complex biological barriers and immunosuppression to promote antitumor efficacy are also summarized. Moreover, past and ongoing trials involving personalized bioactive materials and promising agents such as cell/bacteria-based micro/nano-biorobotics are further discussed, which may become another powerful tool for treatment in the near future.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Bactérias , Humanos , Terapia de Imunossupressão , Neoplasias/tratamento farmacológico , Medicina de Precisão , Microambiente Tumoral
12.
Biomaterials ; 269: 120639, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33434714

RESUMO

Sonodynamic therapy (SDT) is a promising approach for tumor treatment because of the noninvasion, and future would be perfect while it activates systemic immune responses through deep penetration to effectively avoid tumor recurrence. Here, a multifunctional nanosonosensitizer system (FA-MnPs) is designed by encapsulating manganese-protoporphyrin (MnP) into folate-liposomes. The nanoparticles of FA-MnPs not only exhibit excellent depth-responsive SDT but also simultaneously activate SDT-mediated immune response. Under US irradiation, FA-MnPs show the high acoustic intensity in mimic tissue up to 8 cm depth and generate amount of singlet oxygen (1O2). Density functional theory (DFT) calculations reveal that metal coordination in MnP has enhanced the US response ability. The good depth-responsed SDT of FA-MnPs efficiently suppresses the growth of not only the superficial tumors but also the deep lesion in the triple-negative breast cancer (TNBC) mice model. Importantly, FA-MnPs-induced SDT further re-polarizes immunosuppressive M2 macrophages to antitumor M1 macrophages, and elicits immunogenic cell death (ICD) to activate dendritic cells, T lymphocytes, and natural killercells (NK), which consequently trigger the antitumor immune, contributing to the tumor growth inhibition. This study put forward an idea for curing deep-seated and metastatic tumors through noninvasively depth-irradiated immunogenic SDT by reasonably designing multifunctional sonosensitizers.


Assuntos
Neoplasias de Mama Triplo Negativas , Terapia por Ultrassom , Animais , Linhagem Celular Tumoral , Humanos , Lipossomos , Camundongos , Recidiva Local de Neoplasia , Protoporfirinas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
13.
Gene ; 770: 145337, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33278551

RESUMO

BACKGROUND: The myeloma overexpressed gene (MYEOV) plays a critical role in tumorigenesis in a variety of cancers. However, little is known of the prognosis and immune infiltration associated with MYEOV in non-small cell lung cancer (NSCLC). METHODS: We used several databases (Oncomine, TCGA, and GEO) to analysis the expression, prognosis, and immune infiltration, associated with MYEOV in NSCLC. We also used RT-qPCR and immunohistochemistry to investigate the expression and prognosis of MYEOV in NSCLC. RESULTS: Compared with normal tissues, high MYEOV expression in NSCLC was observed in Oncomine database, and was validated in the TCGA database. High MYEOV expression was significantly associated with different subtypes of NSCLC. Moreover, high MYEOV expression was closely related with a poorer overall survival in NSCLC in TCGA cohort, and was validated in GEO database. Simultaneously, high expression of MYEOV correlates with clinical relevance of NSCLC. Specifically, MYEOV expression was negatively correlated with infiltrating levels of tumor purity and B cells in LUAD. MYEOV expression was negatively correlated with infiltrating levels of tumor purity, and positively associated with CD8 + T cells, CD4 + T cells, dendritic cells, and neutrophils in LUSC. GSEA also revealed that high MYEOV expression were enriched in certain cancer-specific pathways. In addition, RT-qPCR and immunohistochemistry showed MYEOV expression was higher in NSCLC compared to the normal tissues. Finally, high MYEOV expression was closely related with poorer overall survival of NSCLC in an independent validation cohort. CONCLUSION: Our analyses indicate that MYEOV can be used as a prognostic biomarker for determining prognosis and immune infiltration in NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Proteínas Proto-Oncogênicas , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Taxa de Sobrevida
14.
Materials (Basel) ; 13(16)2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784570

RESUMO

Although stimuli-responsive release systems have attracted great attention in medical applications, there has been no attempt at "precise" deep profile control based on such systems, which is greatly need to improve oil recovery. With this in mind, we provided a facile and simple strategy to prepare stimuli-responsive composite capsules of amphiphilic dendrimers-poly(styrene sulfonic acid) sodium/halloysite nanotubes (HNTs) via layer-by-layer (LbL) self-assembly technique, controlling the release crosslinking agent methenamine under different pH or salinity conditions. The release time of methenamine encapsulated in multilayer shells is about 40 h, which can be prolonged with the introduction of salt or shortened via the addition of acid, which accordingly induces the gelation of polyacrylamide (PAM) solutions, taking from a few hours to a dozen days. This study provided a novel approach for controllable release of chemical agents and controllable crosslinking of deep profiles in many application fields.

15.
Cancer Manag Res ; 12: 3537-3546, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547191

RESUMO

OBJECTIVE: Diosmetin (DIOS) has been confirmed to possess anti-cancer effects in some types of tumors. However, it remains unclear whether DIOS exerts anti-cancer effects on liver cancer. Thus, our purpose was to observe the effect of DIOS on cell proliferation, cell apoptosis and cell cycle arrest in human liver cancer cells. MATERIALS AND METHODS: The cell viability of HepG2 and HCC-LM3 cells under different concentrations of DIOS was detected using MTT assay. The cell apoptosis and cell cycle arrest were analyzed by flow cytometry. The expression levels of apoptosis/cell cycle-related proteins including P53, Bcl-2, Bax, cleaved-caspase3, cleaved-caspase8, cleaved-PARP, Bak, cdc2, cyclinB1 and P21 were measured using Western blot. HepG2 cells were transfected by checkpoint kinase 1 (Chk1)-small interfering RNA (siRNA) and checkpoint kinase 2 (Chk2)-siRNA, respectively. After that, cell cycle was detected. RESULTS: DIOS significantly suppressed cell proliferation and induced cell apoptosis of HepG2 cells and HCC-LM3 cells. Moreover, DIOS promoted cell cycle arrest in G2/M phase. Western blot results showed that DIOS significantly suppressed the expression levels of Bcl-2, cdc2, cyclinB1, and promoted the expression levels of Bax, cleaved-caspase3, cleaved-caspase8, cleaved-PARP, Bak, P53, and P21. The G2/M phase arrest was observed in HepG2 cells transfected with Chk2-siRNA, while the G2/M phase arrest was not obvious in HepG2 cells transfected with Chk1-siRNA. CONCLUSION: Our findings revealed that DIOS could inhibit cell proliferation and promote cell apoptosis and cell cycle arrest in liver cancer. Furthermore, DIOS could induce G2/M cell cycle arrest in HepG2 cell via targeting Chk2.

16.
J Control Release ; 323: 387-397, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32330573

RESUMO

Chemotherapy is an important modality available for cancer treatment. However, the present chemotherapy is still far from being satisfactory mainly owing to the severe side effects of the chemotherapeutic agents and drug resistance of cancer cells. Thus, reversing drug resistance by constructing an ideal chemotherapeutic strategy with the least side effects and the best efficacy is greatly needed. Here, we designed a smart nanosystem of thermo-sensitive liposome coated gold nanocages with doxorubicin (DOX) loading (LAD) for near-infrared (NIR)-triggered drug release and chemo-photothermal combination therapy. The biocompatible liposomes coating facilitated the cellular uptake of LAD and meanwhile avoided drug leakage during the circulation. More importantly, LAD exhibited controllable photothermal conversion property and produced mild heat under NIR irradiation, which not only triggered DOX release and transferred DOX from lysosome to nucleus, but also elicited the mild heat cell killing effect to improve the curative efficiency. Further mechanism study revealed that mild heat could reverse drug resistance by down-regulation of the chemoresistance-related markers (e.g., HSF-1, p53, P-gp), and inhibited DOX export and increased drug sensitiveness, thereby prominently increased the anticancer efficiency. This versatile nanoplatform with enhanced curative efficacy and lower side effect is promising to apply in the field of drug controlled release and combination tumor therapy.


Assuntos
Ouro , Hipertermia Induzida , Linhagem Celular Tumoral , Doxorrubicina , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos , Temperatura Alta , Fototerapia
17.
ACS Appl Mater Interfaces ; 12(11): 12573-12583, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32119518

RESUMO

Reactive oxygen species (ROS)-mediated cell apoptosis has been a significant strategy for tumor oxidative damage, while tumor hypoxia is a major bottleneck for efficiency. Here, a novel TiO-porphyrin nanosystem (FA-TiOPs) is designed by encapsulating TiO-porphyrin (TiOP) in folate-liposome. The nanosysytem can photocatalyze H2O and tumor-overexpressed H2O2, in situ generating sufficient ROS. TiOP can photosplit water to produce ·OH radical, H2O2, and O2. Generated O2 not only conquers the hypoxia of tumor environment but also can be further excited by TiOP to 1O2 for killing tumor cells. Density functional theory calculations indicate that high energy in excited state (S1) of TiOP and narrow gap energy between S1 and the triplet excited state (Tn) might contribute to the efficient photocatalytic action. Moreover, the generated and overexpressed H2O2 in tumors can also be photocatalyzed to generate 1O2 especially in acid condition, helpful to specific anticancer effect while harmless to normal tissues. This research might pave a new way to bypass the hypoxia-triggered problem for cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Estresse Oxidativo , Hipóxia Tumoral , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Fotólise , Porfirinas/química , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Titânio/química , Titânio/farmacologia , Hipóxia Tumoral/efeitos dos fármacos , Hipóxia Tumoral/efeitos da radiação
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 401-404, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219822

RESUMO

OBJECTIVE: To compare the accuracy of five warfarin-dosing algorithms and warfarin stable dose model (2.5 mg/day) for Shandong population. METHODS: One hundred and twenty five patients who achieved stable warfarin dose were enrolled. Clinical and genetic data were used to evaluate the value of each algorithm by calculating the percentage of patients whose predicted warfarin dose was within 20% of the actual stable therapeutic dose and mean absolute error (MAE). RESULTS: The frequency of patients with CYP2C9*1/*1, CYP2C9*1/*3 and CYP2C9*1/*2 genotype was 92.00%, 7.20%, 0.80%, respectively. That of VKORC1-1639 AA, AG and GG genotype was 82.40%, 15.20%, 2.40%, respectively. CYP4F2*1/*1, *1/*3, *3/*3 genotype was 50.40%, 39.20%, 10.40%, respectively. With the same genotypes for other loci, patients who carried at least one VKORC1-16398G mutant allele had increased warfarin stable daily dose compared with VKORC1-1639AA. Compared with CYP4F2*1/*1, those carrying at least one CYP4F2*3 mutant allele had warfarin stable daily dose increased by 5.9%-13.00%. The percentage of ideal prediction calculated from IWPC model (59.20%), Huang model (57.60%) and Ohno model (52.80%) were higher than others. The MAE were 0.35 (95%CI: 0.11-0.49), 0.15 (95%CI: 0.10-0.32), 0.39 (95%CI: 0.12-0.51), respectively. CONCLUSION: The polymorphisms of CYP2C9, VKORC1 and CYP4F2 genes can influence the stable dose of warfarin in Shandong population. IWPC algorithm is suitable for guiding the use of warfarin in this population.


Assuntos
Anticoagulantes/administração & dosagem , Hidrocarboneto de Aril Hidroxilases , Varfarina/administração & dosagem , Citocromo P-450 CYP2C9/genética , Família 4 do Citocromo P450/genética , Relação Dose-Resposta a Droga , Genótipo , Humanos , Modelos Teóricos , Polimorfismo Genético , Vitamina K Epóxido Redutases/genética
19.
RSC Adv ; 10(13): 7879-7886, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35492168

RESUMO

In this study, gemini ammonium sulfobetaine (GAS) is designed and synthesized using isophorone diisocyanate connecting the ammonium sulfobetaines (AS) to obtain a viscoelastic surfactant exhibiting better viscosification and salt resistance. AS is prepared using the monomers of erucic acid, N-dimethyl-1,3-propanediamine, and 3-chloro-2-hydroxypropanesulfonic acid sodium. The properties of GAS and its proppant suspension as well as the gel-breaking mechanisms are investigated. The critical micelle concentration of GAS is 2.1 × 10-7 mol mL-1. GAS exhibits good salt resistance, and the viscosity is considerably high under acidic conditions. At 0.5 Hz, the storage modulus G' of GAS is 60, 120, and 640 mPa when the concentration is 0.3, 0.5, and 1.0 wt%, respectively. Its proppant suspension is optimal under acidic conditions. When the pH is high, the setting velocities are clearly observed to increase. When the pH is 12, the rate of decline is more than 50% after 200 min. Some of the worm-like micelles adsorbed on the proppant surface participate in the formation of the three-dimensional network, appropriately supporting the proppant-carrying performance. When potassium permanganate is used as the gel breaker, the characterization of the GAS gel-breaking liquid indicates that the double bond is disintegrrated by the gel breaker. Upon gel breaking, the average hydrodynamic radius of the GAS gel-breaking solution decreases to 176.2 nm from 492.3 nm.

20.
RSC Adv ; 10(32): 18721-18727, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35518302

RESUMO

Two new metal-organic coordination polymers (CPs), aqua-2,2'-bipyridine-5-(4'-carboxylphenoxy)isophthalatezinc(ii) polymer [Zn(HL)(2,2'-bipy)(H2O)] n (1) and tris-4,4'-bipyridine-bis-5-(4'-carboxylphenoxy)isophthalatetrizinc(ii) polymer [Zn3(L)2(4,4'-bipy)3] n (2) (H3L = 5-(4'-carboxylphenoxy)isophthalic acid, 4,4'-bipy = 4,4'-bipyridine and 2,2'-bipy = 2,2'-bipyridine), were obtained under hydrothermal conditions and characterized by microanalysis, FTIR spectroscopy and single crystal X-ray diffraction. The single crystal X-ray diffraction indicated that in both the CPs the coordination networks exhibited varied topologies and coordination modes around the Zn(ii) centers. CP 1 exhibits a one-dimensional (1D) chain structure, which further forms a 3D supramolecular architecture via intermolecular π⋯π and hydrogen bonding interactions, while 2 possesses a 3D framework generated from a 2D layered motif comprising zinc and tripodal carboxylate subunits pillared by 4,4'-bpy ligands. Apart from the structural investigation, the photocatalytic performances of both the coordination polymers to photodecompose an aqueous solution of methyl violet (MV) were examined. The results indicated that both the CPs displayed the potential to photodecompose aromatic dyes and in particular 2 showed good photocatalytic activity for dye degradation under light irradiation. The photocatalytic mechanism through which these CPs executed degradation of dyes has been explained with the assistance of band gap calculations using density of states (DOS) and its decomposed partial DOS calculations.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...