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1.
Biosensors (Basel) ; 12(9)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36140121

RESUMO

Diagnostic biomarkers based on epigenetic changes such as DNA methylation are promising tools for early cancer diagnosis. However, there are significant difficulties in directly and specifically detecting methylated DNA regions. Here, we report an electrochemical sensing system based on magnetic nanoparticles that enable a quantitative and selective analysis of the methylated septin9 (mSEPT9) gene, which is considered a diagnostic marker in early stage colorectal cancer (CRC). Methylation levels of SEPT9 in CRC samples were successfully followed by the selective recognition ability of a related peptide nucleic acid (PNA) after hybridization with DNA fragments in human patients' serums and plasma (n = 10). Moreover, this system was also adapted into a point-of-care (POC) device for a one-step detection platform. The detection of mSEPT9 demonstrated a limit of detection (LOD) value of 0.37% and interference-free measurement in the presence of branched-chain amino acid transaminase 1 (BCAT1) and SRY box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1). The currently proposed functional platform has substantial prospects in translational applications of early CRC detection.


Assuntos
Neoplasias Colorretais , Nanopartículas de Magnetita , Ácidos Nucleicos Peptídicos , Aminoácidos de Cadeia Ramificada , Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , DNA , Detecção Precoce de Câncer , Compostos Ferrosos , Humanos , Metalocenos , Septinas/genética , Septinas/metabolismo , Transaminases/metabolismo , Fatores de Transcrição/metabolismo
2.
Arch Biochem Biophys ; 695: 108643, 2020 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-33122162

RESUMO

Artificial nanostructures using polymers to produce polymeric vesicles are inspired by the many intricate structures found in living organisms. Polymersomes are a class of self-assembled vesicles known for their great stability and application in drug delivery. They can be tuned according to their intended use by changing their components and introducing activable block copolymers that transform these polymersomes into smart nanocarriers. In this study, we propose the synthesis of a poly (ethylene oxide)-poly (ε-caprolactone)-based polymersome (PEO-PCL) loaded with GSH as a pH-responsive drug delivery molecule for cancer and protein alteration inhibition. Initially, the nanocarrier was synthesized and characterized by DLS, TEM/SEM microscopy as well as gel permeation chromatography (GPC) and 1H NMR. Their CMC formation, encapsulation efficiency, and pH responsiveness were analyzed. In addition, empty and GSH-loaded PEO-PCL polymersomes were tested for their toxicity and therapeutic effect on normal and cancer cells via an MTT test. Subsequently, protein alteration models (aggregation, glycation, and oxidation) were performed in vitro where the polymersomes were tested. Results showed that other than being non-toxic and able to highly encapsulate and release the GSH in response to acidic conditions, the nanocomposites do not hinder its content's ameliorative effects on cancer cells and protein alterations. This infers that polymeric nanocarriers can be a base for future smart biomedicine applications and theranostics.


Assuntos
Portadores de Fármacos , Glutationa , Proteínas de Neoplasias/metabolismo , Neoplasias , Poliésteres , Animais , Chlorocebus aethiops , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Glutationa/química , Glutationa/farmacocinética , Glutationa/farmacologia , Glicosilação/efeitos dos fármacos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Células Vero
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