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1.
Chem Rev ; 124(9): 5505-5616, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38626459

RESUMO

The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated the creation of more sophisticated drug delivery systems. Polymeric nanoparticles sit at the forefront of numerous promising drug delivery designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, and surface functionality. Furthermore, polymeric nanoparticles have the ability to navigate various biological barriers to precisely target specific sites within the body, encapsulate a diverse range of therapeutic cargo and efficiently release this cargo in response to internal and external stimuli. However, despite these remarkable advantages, the presence of polymeric nanoparticles in wider clinical application is minimal. This review will provide a comprehensive understanding of polymeric nanoparticles as drug delivery vehicles. The biological barriers affecting drug delivery will be outlined first, followed by a comprehensive description of the various nanoparticle designs and preparation methods, beginning with the polymers on which they are based. The review will meticulously explore the current performance of polymeric nanoparticles against a myriad of diseases including cancer, viral and bacterial infections, before finally evaluating the advantages and crucial challenges that will determine their wider clinical potential in the decades to come.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Polímeros , Polímeros/química , Nanopartículas/química , Humanos , Animais , Portadores de Fármacos/química , Neoplasias/tratamento farmacológico
2.
BMC Infect Dis ; 22(1): 892, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443747

RESUMO

BACKGROUND: Neutrophil CD64 (nCD64) index has been widely studied as an indication of bacteria-infected diseases, but the exact usage of nCD64 index in monitoring infections remains debated. So this study aims to investigate the functionality of nCD64 index in tracking infections' progression and evaluating antibiotic therapy. METHODS: 160 participants (36 healthy controls, 34 culture-negative patients, 56 respiratory tract infected patients, and 34 bloodstream infected patients) were recruited and divided into groups. Data on nCD64 index, T lymphocyte subsets, and conventional indicators, including white blood cell count, neutrophil to lymphocyte ratio, procalcitonin, and C-reactive protein, were tested and compared. RESULTS: Bacteria-infected patients had significantly higher nCD64 indexes (p < 0.05), especially patients with both bloodstream and respiratory tract infections. The nCD64 index could identify infected patients from culture-negative patients or controls, which conventional indicators cannot achieve. We followed up with 24 infected patients and found that their nCD64 indexes were promptly down-regulated after effective antibiotic therapy (3.16 ± 3.01 vs. 1.20 ± 1.47, p < 0.001). CONCLUSION: The nCD64 index is a sensitive indicator for clinical diagnosis of bacterial infection, especially in monitoring infection and evaluating antibiotics' efficacy. Therefore, nCD64 has the potential to improve diagnostic accuracy and provide rapid feedback on monitoring disease progression in infected patients.


Assuntos
Infecções Bacterianas , Neutrófilos , Humanos , Estudos de Casos e Controles , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/tratamento farmacológico , Antibacterianos/uso terapêutico , Pró-Calcitonina
3.
Platelets ; 33(7): 1024-1030, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-35040375

RESUMO

Chemotherapy-induced thrombocytopenia (CIT) is a common complication in cancer patients, especially after multiple cycles of chemotherapy, which leads to the delayed treatment or reduced dosage. The treatment of CIT is limited for refractory and severe cases. Herein we reported a single-center study of avatrombopag, a type of thrombopoietin receptor agonist (TPO-RA), for the treatment of severe and refractory (S/R) CIT who failed from multi-line treatments. A total of 13 cancer patients with S/R CIT were enrolled at the First Affiliated Hospital of Zhejiang Chinese Medical University from September 2020 to February 2021. All the patients were administered oral avatrombopag at an initial dose of 60 mg/day, which could be decreased as needed, over a period of 8 weeks. Eight (8/13, 61.5%) patients responded to avatrombopag (with a platelet count ≥50 × 109/L and transfusion independent), with a median response time of 27.5 (11-50) days, and the median cumulative day of platelet response was 79 (20-167). Ten of 13 patients (76.9%) no longer required platelet transfusion at the study endpoint. The predictor of response was the level of hemoglobin (HB) at study entry, patients with an HB over 90 g/L achieved a response rate of 88.9%. In addition, platelet count showed 87.5% sensitivity and 100% specificity to predict the treatment response at a cutoff value of 25.5× 109/L at the end of the third week management. No drug-related side effects were noticed during administration. Our study showed that avatrombopag could be a novel and effective drug for the treatment of severe and refractory CIT, especially for those with hemoglobin above 90 g/L. This study was registered at chictr.org.cn as # ChiCTR2100050646.


Assuntos
Antineoplásicos , Síndromes Mielodisplásicas , Neoplasias , Trombocitopenia , Humanos , Antineoplásicos/uso terapêutico , Síndromes Mielodisplásicas/complicações , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Receptores de Trombopoetina/agonistas , Tiazóis , Tiofenos , Trombocitopenia/induzido quimicamente , Trombocitopenia/etiologia , Trombopoetina/uso terapêutico
4.
Small ; 16(8): e1907043, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32003933

RESUMO

Conjugated coordination polymers (CPs) with designable and predictable structures have drawn tremendous attention in recent years. However, the poor electrical conductivity and low structural stability seriously restrict their practical applications in electronic devices. Herein, the rational design and synthesis of a hierarchically structured 2D bimetallic CoNi-hexaaminobenzene CPs derived from Co(OH)2 are reported as an efficient oxygen evolution reaction (OER) self-supported electrode. The as-obtained electrode possesses high electrochemical surface area and intrinsic activity, exhibiting high electrochemical catalytic activity, favorable reaction kinetics performance, and strong durability compared with those of the powder catalysts. As a result, the electrode delivers low overpotential of 219 mV @ 10 mA cm-2 and Tafel slope of 42 mV dec-1 as well as 91.3% retention of current density after 24 h of reaction time. The results of density functional theory computations reveal that the synergistic effect of Co and Ni plays an important role in OER. This work not only presents a strategy to fabricate advanced self-supported electrodes with abundant and dense active sites, but also promotes the development of conjugated CPs for electrocatalysis.

5.
Nitric Oxide ; 99: 17-24, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32222418

RESUMO

To investigate the association between systemic nitrotyrosine (NT) levels and primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and the mechanism involved. A case control study was conducted in the Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Fudan University from April 2017 to December 2017. A total of 400 participants were consecutively recruited into this study (100 PACG, 100 POAG and 200 controls). Multivariable logistic regression analysis was performed to identify the association between serum NT level and PACG or POAG. Clinical results were validated in cell and animal models. Among 200 glaucoma patients, 101 (50.5%) were women; the age was 57.07 ± 14.51 years. 106 (53%) control participants were women and age was 58.34 ± 14.04 years. Serum levels of NT in PACG and POAG patients are significantly higher than controls (1808.53 ± 417.76 nmol/L vs. 1270.62 ± 454.60 nmol/L, p < 0.001; 1718.63 ± 437.29 nmol/L vs. 1258.38 ± 460.72 nmol/L, p < 0.001). Further, elevated serum NT level increases the risk of developing PACG (OR = 1.003, 95% CI: 1.002 to 1.004, p < 0.001) and POAG (OR = 1.002, 95% CI: 1.002 to 1.003, p < 0.001). Consistent with the clinical data, serum and aqueous humour NT levels are significantly higher in caveolin 1 knockout (Cav1 KO) mice, an animal model of glaucoma. More importantly, peroxynitrite (PN) scavenger MnTMPyP and its transduction molecule PARP inhibitor significantly reduce intraocular pressure in Cav1 KO mice. Our data show for the first time that NT is a systemic risk factor and local treatment target of glaucoma.


Assuntos
Glaucoma de Ângulo Fechado/tratamento farmacológico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Metaloporfirinas/uso terapêutico , Ácido Peroxinitroso/metabolismo , Tirosina/análogos & derivados , Adulto , Idoso , Animais , Estudos de Casos e Controles , Caveolina 1/genética , Feminino , Glaucoma de Ângulo Fechado/sangue , Glaucoma de Ângulo Fechado/metabolismo , Glaucoma de Ângulo Aberto/sangue , Glaucoma de Ângulo Aberto/metabolismo , Humanos , Masculino , Camundongos Knockout , Pessoa de Meia-Idade , Fatores de Risco , Tirosina/sangue , Tirosina/metabolismo
6.
Med Sci Monit ; 24: 4481-4488, 2018 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-29958264

RESUMO

BACKGROUND Serum biomarkers are associated with eye diseases, which results in the need for cryopreservation of serum samples. However, the effect on serum biomarker levels of repeatedly freezing and thawing remains poorly understood. The aim of this study was to evaluate the effects of repeated freeze-thaw on the serum levels of the protein, complement C3c (C3c), the micromolecule, uric acid (UA), and the enzyme, angiotensin-converting enzyme (ACE). MATERIAL AND METHODS Serum samples were obtained from 50 patients who attended an ophthalmic outpatient department. Following baseline measurements, the serum samples from each subject were divided into aliquots and stored at -80°C for further analysis, following between one to six freeze-thaw cycles. The serum levels of C3c, UA, and ACE were measured immediately after the stored serum samples were thawed. RESULTS The serum level of C3c was significantly changed after the first freeze-thaw cycle (p<0.05), and a significant alteration in serum ACE levels occurred after the third freeze-thaw cycle (p<0.05). The serum UA level remained unchanged after all freeze-thaw cycles. Repeated freeze-thaw cycles significantly increased the serum levels of C3c and decreased the serum levels of ACE. The serum levels of C3c, UA, and ACE, respectively were significantly correlated (p<0.001), while the correlation coefficient for C3c and UA were improved when compared with ACE. CONCLUSIONS Repeated freeze-thaw can have variable effects on the serum levels of biomarkers, C3c, UA and ACE, which supports the need for quality control of cryopreserved serum for biomarker evaluation.


Assuntos
Biomarcadores/sangue , Criopreservação/métodos , Congelamento/efeitos adversos , Adulto , Biomarcadores/química , Complemento C3c/análise , Oftalmopatias/sangue , Feminino , Humanos , Masculino , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/sangue , Temperatura , Ácido Úrico/análise , Ácido Úrico/sangue
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(1): 53-6, 2015 Jan.
Artigo em Zh | MEDLINE | ID: mdl-25790675

RESUMO

OBJECTIVE: To evaluate the clinical efficacy of treating myelodysplastic syndrome (MDS) by hematopoietic stem cell transplantation (HSCT) combined with Chinese medical syndrome typing. METHODS: From July 2009 to July 2013, 6 MDS patients were treated with allo-HSCT combined with Chinese medical syndrome typing from HLA-identical sibling donors at Department of Hematology, Zhejiang Provincial Hospital of Chinese Medicine. Patients were classified as refractory anemia (RA, 2 cases), refractory anemia with ringed sideroblast (RARS, 1 case), refractory cytopenia with multilineage dysplasia (RCMD, 2 cases), and RA with excess blasts-I (RAEB-I , 1 case). Modified BuCy conditioning regimen was used in all 6 cases. Two patients received bone marrow transplantation (BMT), 1 patient received peripheral blood stem cell transplantation (PBSCT), and 3 patients received BMT + PBSCT. In order to prevent the occurrence of graft-versus-host disease (GVHD), all patients were treated with cyclosporine + methotrexate + mycophenolate mofetil. Different Chinese medical treatment methods (by syndrome typing) were given to patients according to different criticality of international prognostic scoring system (IPSS, 5 at moderate risk and 1 at high risk). RESULTS: All 6 patients successfully reconstructed their hematopoietic system. The time from transplantation to ANC ≥ 0.5 x 10(9)/L and platelet (PLT) ≥ 20 x10(9)/L were 13 (9-15) days and 11 (9-22) days respectively. Main complications were GVHD. Acute GVHD (aGVHD) occurred in 4 cases, 3 cases of grade I and 1 case of grade II, and local chronic GVHD (cGVHD) occurred in 1 patient. All cases survived with median follow-up of 18 (11-58) months. The overall survival (OS) and disease-free survival (DFS) rate were 100%. CONCLUSIONS: HSCT combined with Chinese medical syndrome typing could improve clinical symptoms, reduce transplant as- sociated complications. So it was an effective treatment choice for MDS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante , Pesquisa Biomédica , Plaquetas , Transplante de Medula Óssea , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Medicamentos de Ervas Chinesas/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Medicina Tradicional Chinesa , Metotrexato/uso terapêutico , Transplante Homólogo , Resultado do Tratamento
8.
ACS Omega ; 8(50): 47773-47780, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38144105

RESUMO

High-entropy alloys have long been used as a new type of alloy material and have attracted widespread concern because of their excellent performance, including their stable microstructure and particular catalytic properties. To design a safer preparation method, we report a novel approach targeting green synthesis, using tea polyphenols to prepare PtPdNiFeCu high-entropy alloy nanoparticles for glucose detection. The fabricated sensors were characterized by transmission electron microscopy and electrochemical experiments. Physical characterization showed that the nanoparticle has better dispersibility, and the average particle size is 7.5 nm. The electrochemical results showed that Tp-PtPdNiFeCu HEA-NPs had a high sensitivity of 1.264 µA mM-1 cm-2, a low detection limit of 4.503 µM, and a wide detection range of 0 - 10 mM. In addition, the sensor has better stability and selectivity for glucose detection.

9.
ACS Nano ; 17(21): 20979-20990, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37906948

RESUMO

Nitric oxide (NO) is a promising approach for treating ocular hypertension and glaucoma. However, its clinical application is limited by its uncontrollable release and the unwanted overproduction of peroxynitrite. Herein, a denitrifying hollow mesoporous organosilica nanoparticle (HMMN) with framework cohybridization is first constructed to encapsulate S-nitroso-N-acetyl-d,l-penicillamine (SNAP) to produce SNAP@HMMN with dual capacities of selective peroxynitrite removal and controllable NO release. Featuring a large corneal permeability, the well-designed SNAP@HMMN can achieve trans-corneal delivery to reach the target trabecular meshwork (TM)/Schlemm's canal (SC) site. Upon light irradiation, the intraocular pressure (IOP) is appropriately lowered in an adjustable and long-lasting manner while the outflow tissues are protected from nitrative damage, which is expected to realize precision on-demand glaucoma therapy with little biosafety concern, promising significant clinical translational potential.


Assuntos
Glaucoma , Óxido Nítrico , Humanos , Ácido Peroxinitroso , Nanomedicina , Glaucoma/tratamento farmacológico , Pressão Intraocular
10.
Biomed Mater ; 18(5)2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37406639

RESUMO

Multi-model combination treatment of malignant tumors can make up for the shortcomings of single treatment through multi-target and multi-path to achieve more ideal tumor treatment effect. However, the mutual interference of different drugs in the delivery processin vivoand the difficulty of effective drug accumulation in tumor cells are the bottlenecks of combined therapy. To this project, light-responsive liposomes loading doxorubicin (DOX) and chlorin e6 (Ce6) (DOX-Ce6-Lip) without mutual interference were engineered by thin film hydration method. This kind of nano-drug delivery system increased the drugs concentration accumulated in tumor sites through enhanced permeability and retention effect, and reduced the toxic and side effects of drugs on normal tissuesin vivo. In addition, after entering the tumor cells, Ce6 produced a large number of reactive oxygen species under 660 nm NIR laser irradiation, which further oxidized the unsaturated fatty acid chain in the liposomes and caused the collapse of the liposomes, thus realizing the stimulus-responsive release of Ce6 and DOX. The concentrations of DOX and Ce6 in the tumor cells rapidly reached the peak and achieved a more effective combination of chemotherapy and photodynamic therapy (PDT). Consequently, DOX-Ce6-Lip followed by 660 nm NIR irradiation achieved an efficient tumor growth inhibition of 71.90 ± 3.14%, indicating the versatile potential of chemotherapy and PDT. In conclusion, this study provides a delivery scheme for drugs with different solubilities and an effectively combined anti-tumor therapy method.


Assuntos
Nanopartículas , Fotoquimioterapia , Neoplasias do Colo do Útero , Feminino , Humanos , Lipossomos , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Linhagem Celular Tumoral , Doxorrubicina/farmacologia
11.
Int J Biol Sci ; 19(11): 3441-3455, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497009

RESUMO

Benign prostatic hyperplasia (BPH) is a condition that becomes more common with age and manifests itself primarily as the expansion of the prostate and surrounding tissues. However, to date, the etiology of BPH remains unclear. In this respect, we performed single-cell RNA sequencing of prostate transition zone tissues from elderly individuals with different prostate volumes to reveal their distinct tissue microenvironment. Ultimately, we demonstrated that a reduced Treg/CD4+ T-cell ratio in the large-volume prostate and a relatively activated immune microenvironment were present, characterized partially by increased expression levels of granzymes, which may promote vascular growth and profibrotic processes and further exacerbate BPH progression. Consistently, we observed that the prostate gland of patients taking immunosuppressive drugs usually remained at a smaller volume. Furthermore, in mouse models, we confirmed that both suppression of the immune system with rapamycin and induction of Treg proliferation with low doses of IL-2 therapy indeed prevented the progression of BPH. Taken together, our findings suggest that an activated immune microenvironment is necessary for prostate volume growth and that Tregs can reverse this immune activation state, thereby inhibiting the progression of BPH.


Assuntos
Hiperplasia Prostática , Humanos , Masculino , Animais , Camundongos , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Interleucina-2 , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Próstata/metabolismo , Modelos Animais de Doenças
12.
Eur J Pharm Sci ; 190: 106570, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37634600

RESUMO

Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic diseases. However, the long desensitization phase and potentially dangerous allergic side effects limit its broad application. Therefore, safer and more effective vaccines are required. Targeting dendritic cells (DCs) with novel allergen conjugates is a promising strategy for AIT. In this study, a novel vaccine with a DC-targeting effect for AIT was constructed. Liposomes were used as vehicles, and a targeted nanovaccine (Lex-lip-Der f 2) was constructed by loading the recombinant group 2 allergen of Dermatophagoides farinae (Der f 2) and conjugating with the DC-SIGN ligand Lewis X. The effect of the vaccine on DCs and T cell responses and the safety of the vaccine were investigated in vitro. The results showed that the Lex-lip-Der f 2 vaccine was spherical, with size of approximately 128 nm. The protein-loading capacity of the vaccine was 0.106 ± 0.001 mg per mg liposome and protein was gradually released from the liposomes during the first 12 h. Lex-lip-Der f 2 was taken up more efficiently by DCs than non-targeted liposomes or free Der f 2. Besides, Lex-lip-Der f 2 significantly inhibited the release of IL-4, IL-6, and TNF-a from DCs. Accordingly, Der f 2-lip loaded DCs significantly decreased IL-4 levels in autologous naïve CD4+T cells. Moreover, Lex-lip-Der f 2-treated basophils showed lower activation levels. These results suggest that DC-SIGN targeting mediated by Lewis X could inhibit the Th2 cell response and improve vaccine safety, and may be a novel vaccination strategy.

13.
Chem Sci ; 13(9): 2510-2527, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35356680

RESUMO

Polyoxometalates (POMs) are anionic molecular metal oxides with expansive diversity in terms of their composition, structure, nuclearity and charge. Within this vast collection of compounds are dominant structural motifs (POM platforms), that are amenable to significant chemical tuning with minimal perturbation of the inorganic oxide molecular structure. Consequently, this enables the systematic investigation of these compounds as inorganic additives within materials whereby structure and charge can be tuned independently i.e. [PW12O40]3- vs. [SiW12O40]4- while also investigating the impact of varying the charge balancing cations on self-assembly. The rich surface chemistry of POMs also supports their functionalisation by organic components to yield so-called inorganic-organic hybrids which will be the key focus of this perspective. We will introduce the modifications possible for each POM platform, as well as discussing the range of nanoparticles, microparticles and surfaces that have been developed using both surfactant and polymer building blocks. We will also illustrate important examples of POM-hybrids alongside their potential utility in applications such as imaging, therapeutic delivery and energy storage.

14.
Biomater Adv ; 133: 112598, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35527140

RESUMO

Combinatorial tumor therapy including chemotherapy and photodynamic therapy (PDT) can compensate for the limitations of each other and significantly increase the therapeutic effect. However, considering the differences of water-soluble characteristics between chemotherapeutic drugs and photosensitizers for photodynamic therapy, simply loading these substances into the same cavities of nanocarriers is rather difficult, leading to the reduced drug loading efficiency. Here, we reported a layered and orthogonal assembly of hydrophilic drugs doxorubicin (Dox) and hydrophobic photosensitizers Chlorin e6 (Ce6) for enhancing the effect of synergistic therapeutics. The assembly was based on polydopamine (PDA) modified with ß-cyclodextrin (ß-CD) through the addition reaction of -HS in HS-ß-CD and-C=C in PDA, then DOX and Ce6 were loaded on the PDA and in the hydrophobic cavities of ß-CDs respectively with superior drug loading efficiencies (38.8 ± 0.8% and 5.4 ± 0.3% for DOX and Ce6). PDA was hydrolyzed completely under the lysosomal acidic condition, leading to the controlled release of DOX. Under NIR irradiations, DOX-based chemotherapy was successfully integrated with PDA-based photothermal and Ce6-based photodynamic therapy. Tumor specific aptamer AS1411-modified assembly provides ideal antitumor effects in vitro and in vivo with excellent biocompatibility. Collectively, this layered and orthogonal assembly offers a generalizable solution for delivering matters with distinct aqueous solubility would find broad applications not only in drug delivery but also in bio-nanotechnology.


Assuntos
Neoplasias , Fotoquimioterapia , Doxorrubicina/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas , Fármacos Fotossensibilizantes/química
15.
Biomed Mater ; 17(6)2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36001994

RESUMO

Chemo-thermotherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. In this study, a novel aptamer functionalized thermosensitive liposome encapsulating hydrophobic drug quercetin was fabricated as an efficient drug delivery system. This aptamer-functionalized quercetin thermosensitive liposomes (AQTSL) combined the merits of high-loading yield, sustained drug release, long-term circulation in the body of PEGylated liposomes, passive targeting provided by 100-200 nm nanoparticles, active targeting and improved internalization effects offered by AS1411 aptamer, and temperature-responsive of quercetin release. In addition, AQTSL tail vein injection combined with 42 °C water bath heating on tumor site (AQTSL + 42 °C)treatment inhibited the tumor growth significantly compared with the normal saline administration (p< 0.01), and the inhibition rate reached 75%. Furthermore, AQTSL + 42 °C treatment also slowed down the tumor growth significantly compared with QTSL combined with 42 °C administration (p< 0.05), confirming that AS1411 decoration on QTSL increased the active targeting and internalization effects of the drug delivery system, and AS1411 aptamer itself might also contribute to the tumor inhibition. These data indicate that AQTSL is a potential carrier candidate for different hydrophobic drugs and tumor targeting delivery, and this kind of targeted drug delivery system combined with temperature responsive drug release mode is expected to achieve an ideal tumor therapy effect.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Lipossomos , Neoplasias/tratamento farmacológico , Quercetina
16.
Int J Nanomedicine ; 17: 3821-3839, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072959

RESUMO

Introduction: During the combined treatment of tumors, the non-interfering transportation of drugs with different solubilities and the controllable sequential release are the main challenges. Here, we reported a double-chamber "Dandelion" -like sequential drug delivery system to realize the sequential release of different drugs for treating malignant tumors synergistically. Methods: After synthesizing mesoporous silica nanoparticles (MSN) by template method, a hydrophilic chemotherapy drug doxorubicin (DOX) was loaded into the channels of mesoporous silica (MSN) and locked with polydopamine (PDA) coating. Next, ß-cyclodextrin (ß-CDs) was decorated on PDA by Michael addition reaction, and the hydrophobic photosensitizer chlorin e6 (Ce6) was encapsulated into the hydrophobic chambers of ß-CDs. Finally, AS1411 was modified on the surface of PDA and obtained DOX@MSN@PDA-ß-CD/Ce6-AS1411 nanoparticles (DMPCCA) through which orthogonal loading and effective controlled release of different drugs were realized. Results: Under the sequential irradiations of 808 nm and 660 nm near-infrared (NIR) laser, PDA promoted the extensive release of Ce6 firstly while playing the effect of photothermal therapy (PTT), further to achieve the effect of photodynamic therapy (PDT) of Ce6. Meanwhile, the rapid release of DOX loaded in MSN channels showed a time lag of about 5 h after Ce6 release, through which it maximized the chemotherapeutic effect. Besides, the present drug loading nano-platform combined passive tumor-targeting effect given by EPR and active tumor-targeting effect endowed by AS1411 realized PTT-PDT-chemotherapy triple mode synergistic combination. Conclusion: We offer a general solution to address the key limitations for the delivery and sequential release of different drugs with different solubilities.


Assuntos
Neoplasias , Fotoquimioterapia , Taraxacum , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Neoplasias/terapia , Dióxido de Silício/química
17.
J Tradit Chin Med ; 31(4): 277-81, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22462231

RESUMO

OBJECTIVE: To probe the effects of qi-supplementing and yin-nourishing therapy (blood-increasing decoction and blood generating powder) on chronic thrombocytopenia. METHODS: Two hundred patients with chronic thrombocytopenia were randomly divided into control (n = 100) and test groups (n = 100) with Amino-polypeptide as a basic treatment for both. Test group patients consumed a blood-increasing decoction and blood-generating powder for 1-3 months. Improvements in platelet counts and TCM syndrome were observed. RESULTS: One hundred and sixty-four (80 in the test group and 84 in the control group) of 189 total participants were treated for 3 months. The total effective rate in improving TCM syndrome was 95.00% in the test group and 79.76% in the control group (P < 0.05). There was significant difference (P < 0.05) in the accumulated score of TCM syndrome between the two groups treated at different time points. The total effective rate of platelet counts was 86.25% in the test group and 59.52% in the control group (P < 0.05). There was a significant difference in platelet counts before and after treatment in the two groups (P < 0.05). There was no significant differences in platelet count between the two groups treated for 1-2 months; however, a significant difference was found between the two groups after treatment for 3 months (P < 0.05). CONCLUSIONS: After a 3-month treatment of chronic thrombocytopenia patients with qi-supplementing and yin-nourishing therapy, TCM syndrome was improved and platelet counts increased with no obvious side effects, and the quality of life of the participants was enhanced with noticeable long-term curative effects.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Qi , Trombocitopenia/tratamento farmacológico , Deficiência da Energia Yin/tratamento farmacológico , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/uso terapêutico , Contagem de Plaquetas , Trombocitopenia/sangue , Deficiência da Energia Yin/sangue , Adulto Jovem
18.
Org Lett ; 23(22): 9000-9005, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34748354

RESUMO

An efficient iodine-imine synergistic promoted Povarov-type multicomponent reaction was reported for the synthesis of a practical 2,2'-biquinoline scaffold. The tandem annulation has reconciled iodination, Kornblum oxidation, and Povarov aromatization, where the methyl group of the methyl azaarenes represents uniquely reactive input in the Povarov reaction. This method has broad substrate scope and mild conditions. Furthermore, these 2,2'-biquinoline derivatives had been directly used as bidentate ligands in metal-catalyzed reactions.

19.
Front Oncol ; 11: 793773, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35071002

RESUMO

We evaluated the predictive value of the ex-vivo PharmaFlow PM platform in measuring the pharmacological activity of drug combinations consisting of 20 different chemotherapy regimens (20 Tx) administered in 104 acute myeloid leukemia (AML) patients. The predicted sensitivities of alternative treatments for each patient were ranked in five 20% categories, from resistant to sensitive (Groups 1-5). The complete remission (CR) rates of the five groups were 0%, 12.5%, 38.5%, 50.0%, and 81.3%, respectively. The heat map showed a good relationship between drug sensitivity with CR (Group 4 + 5 vs. Group 1 + 2+3: 77.5% vs. 27.3%, p = 0.002) and the European Leukemia Net risk group (22.6% vs. 63.6%, p = 0.015). The predicted coincidence rate was 90.9% in Group 1 + 2 and 81.3% in Group 5. According to the recommendations of the PharmaFlow PM platform, the CR rate would have increased by about 16.3% in one cycle. The overall survival (OS) was shorter in patients predicted to be resistant (Group 1 + 2 vs. Group 3 + 4+5, p = 0.086). In multivariable analysis, CR after one cycle was an independent prognostic factor for OS [p = 0.001; 95% CI 0.202 (0.080-0.511)], and ex-vivo chemosensitivity was a potential predictive factor for OS [p = 0.078; 95% CI 0.696 (0.465-1.041)]. To conclude, the PharmaFlow PM platform is a rapid and valuable tool for predicting clinical response and outcomes in AML patients.

20.
Data Brief ; 31: 105706, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32490078

RESUMO

From April to December 2017, the case-control data were collected in the Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Fudan University. One hundred primary angle closure glaucoma (PACG), one hundred primary open angle glaucoma (POAG) patients and two hundred control participants were consecutively recruited. The serum nitrotyrosine (NT) levels was not significant different in PACG or POAG patients stratified by gender (1,868.17±427.13 nmol/L vs. 1,768.77±410.17 nmol/L, p>0.05; 1,734.04±460.74 vs. 1,696.46±405.73 nmol/L, p>0.05). Serum NT level was not significantly associated with glaucoma severity in either PACG group or POAG group based on mean deviation (MD) (mild, n=30; moderate, n=24; sever, n=19; blinding, n=27, p>0.05, in Table 3 for PACG; mild, n=9; moderate, n=20; sever, n=21; blinding, n=40; p>0.05, in Table 4 for POAG). Multivariable logistic regression analysis indicated that the risk of developing PACG were significantly associated with serum total triglyceride (TG) and uric acid (UA) levels (OR=1.638, 95%CI: 1.059-2.531, p=0.026 for TG, OR=0.003, 95%CI: 0-0.461, p=0.024 for UA). Serum TG, gamma-glutamyl transferase (GGT) and total bilirubin (TB) levels were significantly associated with POAG (OR=2.00, 95%CI: 1.363-2.934, p<0.001 for TG; OR=0.972, 95%CI: 0.949-0.996, p=0.022 for GGT; OR=1.115, 95%CI: 1.042-1.194, p=0.002 for TB). Descriptions of the data are also available in our recent paper published in Nitric Oxide, "Peroxynitrite is a novel risk factor and treatment target of glaucoma" [1].

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