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1.
Small ; 20(13): e2308621, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38109130

RESUMO

Neuropeptide Y (NPY), as one of the most abundant neuropeptides known, is widely distributed in the central and peripheral nervous system. However, most of the reported NPY-mimetic peptides are hard to cross the blood-brain barrier, target glioma mitochondria, and achieve self-assembly nanostructure in situ. Here, based on the α-helix structure of the novel chiral NPY-mimetic peptides D/LNPY(14), a Y-shaped peptide is designed with the sequences that can be recognized by enterokinase and achieved nanofibers conversion in glioma cell mitochondria. Coupling the Y-shaped NPY-mimetic peptide with the NIR-II fluorophore IR1048, a red-shifting of the fluorescence spectrum beyond 1300 nm is achieved through self-assembly. After the self-assembly in glioma mitochondria, the formed nanofibers can promote intracellular mitochondrial ROS production and extend the NIR-II fluorescence imaging time to at least 7 days in vivo. This work for the first time endows the self-assembly of α-helical-based chiral NPY-mimetic peptides, providing a novel strategy for glioma subcellular regulation enhanced antitumor treatment guided by NIR-II fluorescence imaging.


Assuntos
Neuropeptídeo Y , Receptores de Neuropeptídeo Y , Receptores de Neuropeptídeo Y/metabolismo , Barreira Hematoencefálica/metabolismo
2.
Bioconjug Chem ; 34(6): 1157-1165, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37235785

RESUMO

Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype due to its lack of targeted therapies and poor prognosis. In order to treat patients with these tumors, efforts have been made to explore feasible targets. Epidermal growth factor receptor (EGFR)-targeted therapy is currently in clinical trials and regarded to be a promising treatment strategy. In this study, an EGFR-targeting nanoliposome (LTL@Rh2@Lipo-GE11) using ginsenoside Rh2 as a wall material was developed, in which GE11 was used as the EGFR-binding peptide to deliver more ginsenoside Rh2 and luteolin into TNBC. In comparison to non-targeted liposomes (Rh2@Lipo and LTL@Rh2@Lipo), the nanoliposomes LTL@Rh2@Lipo-GE11 demonstrated a high specificity to MDA-MB-231 cells that expressed a high level of EGFR both in vitro and in vivo, contributing to the strong inhibitory effects on the growth and migration of TNBC. These results suggest that LTL@Rh2@Lipo-GE11 is a prospective candidate for targeted therapy of TNBC, with a remarkable capability to inhibit tumor development and metastasis.


Assuntos
Ginsenosídeos , Neoplasias de Mama Triplo Negativas , Humanos , Lipossomos/uso terapêutico , Neoplasias de Mama Triplo Negativas/metabolismo , Receptores ErbB/metabolismo , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Linhagem Celular Tumoral
3.
ACS Nano ; 16(11): 19038-19052, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36315056

RESUMO

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (·OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on ·OH, low intracellular H2O2 level, and low reaction rate, resulting in unsatisfactory efficacy. Here, a cancer cell membrane (CM)-camouflaged Au nanorod core/mesoporous MnO2 shell yolk-shell nanocatalyst embedded with glucose oxidase (GOD) and Dox (denoted as AMGDC) is constructed for synergistic triple-augmented CDT and chemotherapy of tumor under MRI/PAI guidance. Benefiting from the homologous adhesion and immune escaping property of the cancer CM, the nanocatalysts can target tumor and gradually accumulate in tumor site. For triple-augmented CDT, first, the MnO2 shell reacts with intratumoral GSH to generate Mn2+ and glutathione disulfide, which achieves Fenton-like ion delivery and weakening of GSH-mediated scavenging effect, leading to GSH depletion-enhanced CDT. Second, the intratumoral glucose can be oxidized to H2O2 and gluconic acid by GOD, achieving supplementary H2O2-enhanced CDT. Next, the AuNRs absorbing in NIR-II elevate the local tumor temperature upon NIR-II laser irradiation, achieving photothermal-enhanced CDT. Dox is rapidly released for adjuvant chemotherapy due to responsive degradation of MnO2 shell. Moreover, GSH-activated PAI/MRI can be used to monitor CDT process. This study provides a great paradigm for enhancing CDT-mediated antitumor efficacy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Biomimética , Peróxido de Hidrogênio/metabolismo , Compostos de Manganês/farmacologia , Linhagem Celular Tumoral , Óxidos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Glutationa/metabolismo , Glucose Oxidase/metabolismo , Microambiente Tumoral
4.
Anal Chim Acta ; 1203: 339688, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35361430

RESUMO

Methylglyoxal (MGO), a dicarbonyl compound in living organism, food and environment, has been associated with disease diagnosis and human health. The current electrochemical detection methods rely on the use of advanced materials. In this work, a non-advanced materials "two-step" assay including electrode electro-activation and MGO detection was developed. In the section of electro-activation, an activation method of GCE for MGO detection was established; and the composition changes on GCE surface caused by electro-activation, including functional groups and surface defects, have been carefully studied. The effect of carbonyl and surface defects induced by electro-activation on MGO detection was discussed. In section of MGO detection, the raise of background current caused by electro-activation was minimized by background subtraction; and the effect of interferences can be weakened by adjusting pH. The MGO signal on proposed activated GCE improved 20-fold than bare GCE. The recoveries were 72.38-109.16% in honey and beer, and RSDs were 0.24-9.63% without significant difference with HPLC method and comparable with advanced material modified sensors.


Assuntos
Mel , Aldeído Pirúvico , Cerveja , Técnicas Eletroquímicas , Eletrodos , Humanos , Aldeído Pirúvico/análise , Aldeído Pirúvico/farmacologia
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