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1.
Angew Chem Int Ed Engl ; 63(10): e202318372, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38205971

RESUMO

The site-specific activation of bioorthogonal prodrugs has provided great opportunities for reducing the severe side effects of chemotherapy. However, the precise control of activation location, sustained drug production at the target site, and high bioorthogonal reaction efficiency in vivo remain great challenges. Here, we propose the construction of tumor cell membrane reactors in vivo to solve the above problems. Specifically, tumor-targeted liposomes with efficient membrane fusion capabilities are generated to install the bioorthogonal trigger, the amphiphilic tetrazine derivative, on the surface of tumor cells. These predecorated tumor cells act as many living reactors, transforming the tumor into a "drug factory" that in situ activates an externally delivered bioorthogonal prodrug, for example intratumorally injected transcyclooctene-caged doxorubicin. In contrast to the rapid elimination of cargo that is encapsulated and delivered by liposomes, these reactors permit stable retention of bioorthogonal triggers in tumor for 96 h after a single dose of liposomes via intravenous injection, allowing sustained generation of doxorubicin. Interestingly, an additional supplement of liposomes will compensate for the trigger consumed by the reaction and significantly improve the efficiency of the local reaction. This strategy provides a solution to the efficacy versus safety dilemma of tumor chemotherapy.


Assuntos
Compostos Heterocíclicos , Neoplasias , Pró-Fármacos , Humanos , Pró-Fármacos/uso terapêutico , Lipossomos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Doxorrubicina/uso terapêutico
2.
Anal Chem ; 95(48): 17834-17842, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-37988125

RESUMO

Precise and sensitive analysis of exosomal microRNA (miRNA) is of great importance for noninvasive early disease diagnosis, but it remains a great challenge to detect exosomal miRNA in human blood samples because of their small size, high sequence homology, and low abundance. Herein, we integrated reliable Pt-S bond-mediated three-dimensional (3D) DNA nanomachine and magnetic separation in a homogeneous electrochemical strategy for the detection of exosomal miRNA with low background and high sensitivity. The 3D DNA nanomachine was easily prepared via a facile and rapid freezing method, and it was capable of resisting the influence of biothiols, thus endowing it with high stability. Notably, the as-developed magnetic 3D DNA nanomachine not only enabled the detection system to have a low background but also coupled with liposome nanocarriers to synergistically amplify the current signal. Consequently, by ingeniously combining the low background and multiple signal-amplification strategies in homogeneous electrochemical biosensing, highly sensitive detection of exosomal miRNA was successfully achieved. More significantly, with good anti-interference ability, the as-proposed method could effectively discriminate plasma samples from cancer patients and healthy subjects, thus showing a high potential for application in the nondestructive early clinical diagnosis of disease.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Humanos , MicroRNAs/análise , DNA/análise , Lipossomos , Fenômenos Físicos , Fenômenos Magnéticos , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Limite de Detecção
3.
Respir Res ; 23(1): 175, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35778703

RESUMO

BACKGROUND: Sputum biopsies offer unique advantages such as non-invasiveness and convenient collection. The one investigation so far on sputum for genome profiling in advanced non-small cell lung cancer (aNSCLC) suggested promising performance. However, it remains undefined whether clinicohistologic characteristics were associated with performance and how this knowledge could help guide choice of liquid biopsy. METHODS: Targeted sequencing with a 520-gene panel was performed on prospectively collected matched tumor tissue (TIS), plasma (PLA), and sputum supernatant (SPU) from 71 aNSCLC patients (NCT05034445). Genomic alteration detection was characterized in a series of aspects and interrogated for association with 14 clinicohistologic features. Nomograms were constructed with logistic regression for predicting the liquid biopsy type with greater sensitivity. RESULTS: Compared with PLA, SPU showed comparable quality control metrics, mutation detection rate (SPU: 67.6%, PLA: 70.4%), concordance with tumor tissue (67.6% vs. 73.2%), and correlation with tissue-based tumor mutation burden levels (r = 0.92 vs. 0.94). For driver alterations, detection was less sensitive with SPU (50.0%) than PLA (63.5%) in the entire cohort but similarly or more sensitive in patients with centrally located lung tumors or smoking history or for altered ALK or KRAS. Two nomograms were constructed and enabled predicting the probability of superior sensitivity with SPU with moderate to borderline high accuracy. CONCLUSION: In addition to demonstrating comparable performance in multiple aspects, this study is the first to propose nomograms for choosing liquid biopsy based on clinicohistologic characteristics. Future research is warranted to delineate the clinical utility of sputum for genome profiling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos Clínicos como Assunto , Humanos , Biópsia Líquida , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Poliésteres , Escarro
4.
Chemistry ; 27(67): 16722-16734, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34632663

RESUMO

Helical architectures with controllable helical sense bias have recently attracted considerable interest for mimicking biological helices and developing novel chiral materials. Coordination polymers (CPs), composed of metal ion nodes and organic linkers, are intriguing systems showing tunable structures and functions. However, CPs with helical morphologies have rarely been explored so far. Particularly, chirality inversion through external stimulus has not been achieved in helical CPs. In this work, we carried out an in-depth investigation on the self-assembly of 1D gadolinium(III) phosphonate CPs using GdX3 (X=Cl, Br, I) and Gd(RSO3 ) (R=CH3 , C6 H5 , CF3 ) as metal sources and R-(1-phenylethylamino)methyl phosphonic acid (R-pempH2 ) as ligand. Superhelices were formed by precise control of the interchain interactions through different intercalated anions. Furthermore, the twisting direction of superhelices could be controlled by synergistic effect of anions and pH. This study may provide a new route to fabricate helical nanostructures of CPs with a desirable chiral sense and help understand the inner mechanism of the self-assembly process of macroscopic helical structures of molecular systems.


Assuntos
Nanoestruturas , Polímeros , Ânions , Concentração de Íons de Hidrogênio , Estereoisomerismo
5.
J Oral Maxillofac Surg ; 73(1): 81-91, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25511958

RESUMO

PURPOSE: The relative frequency of individual minor salivary gland tumors (MSGTs) is not well documented in the literature. The aim of this study was to determine the range and demographics of all histologically diagnosed MSGTs in a northeastern Chinese population. MATERIALS AND METHODS: A total of 485 cases of MSGT were retrospectively studied. The files of the Department of Oral and Maxillofacial Pathology, School of Stomatology, China Medical University served as a source of material for this study. All epithelial tumors from minor salivary glands accessioned from August 2004 to April 2014 were analyzed for demographic features, anatomic location of tumors, and pathologic classification. Tumors were classified according to the 2005 World Health Organization classification of salivary gland tumors. Statistical analysis was performed using analysis of variance. RESULTS: MSGTs were identified in 485 (2.60%) of 18,670 accessed cases. There were 268 (55.26%) benign and 217 (44.74%) malignant tumors. Female outnumbered male patients (male-to-female ratio, 1:1.43). The mean ages of patients with benign and malignant MSGTs were 47.58 and 51.51 years, respectively. Pleomorphic adenoma and adenoid cystic carcinoma were the most frequent types of benign and malignant tumors, respectively. The palate was the most commonly affected site (64.74%), followed by the buccal mucosa (7.63%) and the tongue (5.98%). CONCLUSIONS: From the results of this study and a review of the literature, it is suggested that MSGTs in the northeastern Chinese population may be characterized by a higher incidence of MSGTs than in the populations of other reviewed regions, a higher incidence of myoepithelioma, a rarer occurrence of polymorphous low-grade adenocarcinoma, and an absence of canalicular adenoma occurrence.


Assuntos
Neoplasias das Glândulas Salivares/epidemiologia , Glândulas Salivares Menores/patologia , Adenocarcinoma/epidemiologia , Adenoma Pleomorfo/epidemiologia , Fatores Etários , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Mucoepidermoide/epidemiologia , Bochecha/patologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mioepitelioma/epidemiologia , Palato/patologia , Estudos Retrospectivos , Fatores Sexuais , Língua/patologia
6.
Zhongguo Zhong Yao Za Zhi ; 36(7): 864-7, 2011 Apr.
Artigo em Zh | MEDLINE | ID: mdl-21761723

RESUMO

OBJECTIVE: To compare the pharmaceutical properties and the anti-tumor activities of three kinds of stealth liposomes prepared with different phospholipid composition containing brucine. METHOD: Stealth liposomes with different phospholipids composition, such as soybean phosphatidycholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC) and the complex of SPC and HSPC, were prepared by ammonium sulfate transmembrane gradient method. Pharmaceutical properties such as shape, encapsulation efficiency and size of three stealth liposomes were compared intensively. Anti-tumor activity of SPC, HSPC and novel stealth liposomes composed of both SPC and HSPC were compared by established mouse liver cancer H22 model. Meanwhile, the mice body weight and immune organ weight were also compared. RESULT: The encapsulation efficiency of novel, SPC and HSPC stealth liposomes were 77.7%, 64.8% and 74.8%, respectively. The mean diameters of them were less than 100 nm. The tumor inhibition rate of novel, HSPC and SPC stealth liposomes were 57.88%, 49.15%, 23.37%, respectively. The mice body weight, thymus gland index of three stealth liposomes group and spleen index of novel stealth liposomes group had no significant difference with the negative group while SPC and HSPC stealth liposomes group increased the spleen index. CONCLUSION: Phospholipids composition is the key factor which determines the antitumor activity of brucine-loaded stealth liposomes.


Assuntos
Antineoplásicos/farmacologia , Lipossomos/química , Fosfolipídeos/química , Estricnina/análogos & derivados , Animais , Antineoplásicos/química , Peso Corporal/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Lipossomos/efeitos adversos , Camundongos , Tamanho da Partícula , Estricnina/química
7.
Zhongguo Zhong Yao Za Zhi ; 36(10): 1353-7, 2011 May.
Artigo em Zh | MEDLINE | ID: mdl-21837982

RESUMO

OBJECTIVE: To compare the pharmacokinetic characteristics of brucine following intravenous administration of liposomes, containing total alkaloids from seed of Strychnos nux-vomica, to rats with different phospholipids composition. METHOD: Liposomes containing the total alkaloids were prepared by the method of ammonium sulfate transmembrane gradients and stealth liposome technique. The contents of total alkaloids and brucine in liposomes were determined and compared after free drug being removed. After intravenous administration of total alkaloids solution or liposomes with different composition, plasma samples were drawn at predetermined time points and the concentrations of brucine were determined by a validated method of HPLC. Pharmacokinetic analysis was performed by 3P97 program. RESULT: The ratios of brucine to total alkaloids in liposomes hardly varied with phospholipids composition. Compared with SPC liposome, AUC of brucine was increased 13.3-fold and apparent volume of distribution was decreased to only 3.6% following intravenous administration of HSPC liposome. In addition, besides that AUC of brucine was slightly increased, most pharmacokinetic parameters were not significantly changed after administration of the novel liposome compared with those of SPC liposome. CONCLUSION: Phospholipids composition has a significant influence on the pharmacokinetics of brucine after intravenous administration of liposomes containing total alkaloids from seed of S. nux-vomica.


Assuntos
Alcaloides/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Estricnina/análogos & derivados , Strychnos nux-vomica/química , Alcaloides/administração & dosagem , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Infusões Intravenosas , Lipossomos/administração & dosagem , Lipossomos/farmacocinética , Masculino , Modelos Animais , Ratos , Ratos Sprague-Dawley , Sementes/química , Estricnina/administração & dosagem , Estricnina/farmacocinética
8.
Biosci Rep ; 38(1)2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29229675

RESUMO

PEG-PLGA nanoparticles (NPs) modified with anti-CD133 and tumor-targeting single-chain antibody fragment (scFV-NPs) for systemic delivery of methioninase (METase) and pemetrexed for gastric carcinoma were successfully formulated. The structure characterization and biological functions of METase-pemetrexed-loaded scFV-PEG-PLGA NPs (scFV-METase/pemetrexed-NPs) in vitro were investigated. Functional scFV-PEG-PLGA NPs or PEG-PLGA NPs present low cell cytoxicity in CD133+ SGC7901 cells. scFV-METase/pemetrexed-NPs (scFv-M/P-NP) was more effective in inhibiting tumor growth (including cell growth and migration ability) in CD133 positive expressed gastric cancer cells than METase/pemetrexed-NPs (M/P-NP). Moreover, METase enhanced the inhibitory effect of pemetrexed on thymidylate synthase (TS) synthesis and cell apoptosis. We have demonstrated the application of scFV-targeted PEG-PLGA NPs as a new potential strategy to enhance treatment benefits for gastric carcinoma.


Assuntos
Ácido Láctico/administração & dosagem , Nanopartículas/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Anticorpos de Cadeia Única/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Antígeno AC133/administração & dosagem , Antígeno AC133/química , Liases de Carbono-Enxofre/administração & dosagem , Liases de Carbono-Enxofre/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Humanos , Ácido Láctico/química , Nanopartículas/química , Pemetrexede/química , Poliésteres/administração & dosagem , Poliésteres/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Anticorpos de Cadeia Única/química , Neoplasias Gástricas/patologia
9.
Br J Oral Maxillofac Surg ; 53(2): 132-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25457627

RESUMO

Little information has been published in English about the epidemiology of tumours of the salivary glands in northeastern China. From August 2004 to March 2014, 2508 cases of primary epithelial salivary gland tumours were diagnosed in the Department of Oral and Maxillofacial Surgery, the Affiliated Stomatology Hospital of China Medical University. Tumours were analysed according to their histological type and site, and the age and sex of the patients. Ages ranged from 5 to 98 years, with a slight propensity in favour of men. The peak incidence was in the sixth decade for both sexes. The mean (SD) ages were 48 (16) years when the tumour was benign and 51 (15) years when it was malignant. The parotid gland and palate were the sites most commonly affected. There were 1934 (77.1%) benign and 574 (22.9%) malignant tumours, with the most common histological types being pleomorphic adenomas and mucoepidermoid carcinomas. A lesion that arises from the floor of the mouth (92.8%) or the tongue (86.2%) is more likely to be malignant than those from other minor salivary glands.


Assuntos
Neoplasias das Glândulas Salivares/epidemiologia , Adenolinfoma/epidemiologia , Adenoma/epidemiologia , Adenoma Pleomorfo/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Adenoide Cístico/epidemiologia , Carcinoma Mucoepidermoide/epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mioepitelioma/epidemiologia , Neoplasias Palatinas/epidemiologia , Neoplasias Parotídeas/epidemiologia , Estudos Retrospectivos , Glândulas Salivares Menores/patologia , Fatores Sexuais , Neoplasias da Glândula Submandibular/epidemiologia , Adulto Jovem
10.
Int J Pharm ; 450(1-2): 145-62, 2013 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-23632262

RESUMO

Polyurethanes (PUs) are formed by a reaction between isocyanates and diols to yield polymers with urethane bonds (-NH-COO-) in their main chain. A great variety of building blocks is commercially available that allows the chemical and physical properties of PUs to be tailored to their target applications, particularly for the biomedical and pharmaceutical fields. This article reviews the synthesis and characterization of PUs and PU-copolymers, as well as their in vitro and in vivo biodegradability and biocompatibility. Particular emphasis is placed on the use of PUs for the controlled release of drugs and for the (targeted) delivery of biotherapeutics.


Assuntos
Sistemas de Liberação de Medicamentos , Poliuretanos/química , Animais , Humanos
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