Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
Add more filters










Database
Language
Publication year range
1.
Expert Opin Drug Discov ; 18(12): 1321-1332, 2023.
Article in English | MEDLINE | ID: mdl-37661858

ABSTRACT

INTRODUCTION: Graphene-based materials (GBMs) have unique physicochemical properties that make them extremely attractive as platforms for the design of new drugs. Indeed, their bidimensional (2D) morphology, high surface area, mechanical and optical properties, associated to different possibilities for functionalization of their surface, provides opportunities for their use as nanomedicines for drug delivery and/or phototherapies. AREAS COVERED: This opinion paper provides an overview of the current status of GBMs in drug design, with a focus on their therapeutic applications, potential environmental and health risks, and some controversial results. The authors discuss the chemical modifications of GBMs for the treatment of various diseases. The potential toxicity associated with some GBMs is also presented, along with a safe-by-design approach to minimize the risks. Finally, the authors address some issues associated to the use of GBMs in the biomedical field, such as contradictory antibacterial effects, fluorescence quenching and imprecise chemical functionalization. EXPERT OPINION: GBMs are a promising and exciting area of research in drug delivery. It is however important that responsible and safe use of these materials is ensured to fully exploit their advantages and overcome their drawbacks.


Subject(s)
Graphite , Nanostructures , Humans , Graphite/chemistry , Graphite/toxicity , Nanostructures/chemistry , Nanostructures/toxicity , Drug Delivery Systems , Nanomedicine , Drug Design
2.
Front Cell Infect Microbiol ; 13: 1209563, 2023.
Article in English | MEDLINE | ID: mdl-37415828

ABSTRACT

Introduction: The antibacterial activity of graphene oxide (GO) has been widely explored and tested against various pathogenic bacterial strains. Although antimicrobial activity of GO against planktonic bacterial cells was demonstrated, its bacteriostatic and bactericidal effect alone is not sufficient to damage sedentary and well protected bacterial cells inside biofilms. Thus, to be utilized as an effective antibacterial agent, it is necessary to improve the antibacterial activity of GO either by integration with other nanomaterials or by attachment of antimicrobial agents. In this study, antimicrobial peptide polymyxin B (PMB) was adsorbed onto the surface of pristine GO and GO functionalized with triethylene glycol. Methods: The antibacterial effects of the resulting materials were examined by evaluating minimum inhibitory concentration, minimum bactericidal concentration, time kill assay, live/dead viability staining and scanning electron microscopy. Results and discussion: PMB adsorption significantly enhanced the bacteriostatic and bactericidal activity of GO against both planktonic cells and bacterial cells in biofilms. Furthermore, the coatings of PMB-adsorbed GO applied to catheter tubes strongly mitigated biofilm formation, by preventing bacterial adhesion and killing the bacterial cells that managed to attach. The presented results suggest that antibacterial peptide absorption can significantly enhance the antibacterial activity of GO and the resulting material can be effectively used not only against planktonic bacteria but also against infectious biofilms.


Subject(s)
Anti-Infective Agents , Graphite , Polymyxin B/pharmacology , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Graphite/pharmacology , Biofilms , Bacteria , Microbial Sensitivity Tests
3.
J Control Release ; 317: 109-117, 2020 01 10.
Article in English | MEDLINE | ID: mdl-31778740

ABSTRACT

Subcellular delivery of nanomedicines has emerged as a promising approach to enhance the therapeutic efficacy of anticancer drugs. Nuclear accumulation of anticancer drugs are essential for its therapeutic efficacy because their targets are generally located within the nucleus. However, strategies for the nuclear accumulation of nanomedicines with anticancer drugs rarely reported. In this study, we reported a promising nanomedicine, comprising a drug-peptide amphiphile, with enhanced cellular uptake and nuclear accumulation capability for cancer therapy. The drug-peptide amphiphile consisted of the peptide ligand PMI (TSFAEYWNLLSP), which was capable of activating the p53 gene by binding with the MDM2 and MDMX located in the cell nucleus. Peptide conformations could be finely tuned by using different strategies including heating-cooling and enzyme-instructed self-assembly (EISA) to trigger molecular self-assembly at different temperatures. Due to the different peptide conformations, the drug-peptide amphiphile self-assembled into nanomedicines with various properties, including stabilities, cellular uptake, and nuclear accumulation. The optimized nanomedicine formed by EISA strategy at a low temperature of 4 °C showed enhanced cellular uptake and nuclear accumulation capability, and thus exhibited superior anticancer ability both in vitro and in vivo. Overall, our study provides a useful strategy for finely tuning the properties and activities of peptide-based supramolecular nanomaterials, which may lead to optimized nanomedicines with enhanced performance.


Subject(s)
Antineoplastic Agents , Nanostructures , Pharmaceutical Preparations , Nanomedicine , Peptides
4.
Chem Commun (Camb) ; 55(50): 7175-7178, 2019 Jun 25.
Article in English | MEDLINE | ID: mdl-31162503

ABSTRACT

The identification and removal of senescent cells is very important to improve human health and prolong life. In this study, we introduced a novel strategy of ß-galactosidase (ß-Gal) instructed peptide self-assembly to selectively form nanofibers and hydrogels in senescent cells. We demonstrated that the in situ formed nanofibers could alleviate endothelial cell senescence by reducing p53, p21, and p16INK4a expression levels. We also demonstrated that our strategy could selectively remove senescent endothelial cells by inducing cell apoptosis, with an increase in the BAX/BCL-2 ratio and caspase-3 expression. Our study reports the first example of enzyme-instructed self-assembly (EISA) by a sugar hydrolase, which may lead to the development of supramolecular nanomaterials for the diagnosis and treatment of many diseases, such as cancer, and for other applications, such as wound healing and senescence.


Subject(s)
Cellular Senescence/drug effects , Human Umbilical Vein Endothelial Cells/physiology , Nanofibers , beta-Galactosidase/metabolism , Gene Expression Regulation , Humans , Hydrolases/metabolism , Lipopolysaccharides/toxicity
5.
Research (Wash D C) ; 2019: 4803624, 2019.
Article in English | MEDLINE | ID: mdl-31912037

ABSTRACT

The selective formation of nanomaterials in cancer cells and tumors holds great promise for cancer diagnostics and therapy. Until now, most strategies rely on a single trigger to control the formation of nanomaterials in situ. The combination of two or more triggers may provide for more sophisticated means of manipulation. In this study, we rationally designed a molecule (Comp. 1) capable of responding to two enzymes, alkaline phosphatase (ALP), and reductase. Since the A549 lung cancer cell line showed elevated levels of extracellular ALP and intracellular reductase, we demonstrated that Comp. 1 responded in a stepwise fashion to those two enzymes and displayed a tandem molecular self-assembly behavior. The selective formation of nanofibers in the mitochondria of the lung cancer cells led to the disruption of the mitochondrial membrane, resulting in an increased level of reactive oxygen species (ROS) and the release of cytochrome C (Cyt C). ROS can react with proteins, resulting in endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). This severe ER stress led to disruption of the ER, formation of vacuoles, and ultimately, apoptosis of the A549 cells. Therefore, Comp. 1 could selectively inhibit lung cancer cells in vitro and A549 xenograft tumors in vivo. Our study provides a novel strategy for the selective formation of nanomaterials in lung cancer cells, which is powerful and promising for the diagnosis and treatment of lung cancer.

6.
Nanoscale ; 10(45): 21459-21465, 2018 Dec 07.
Article in English | MEDLINE | ID: mdl-30427030

ABSTRACT

Peptide-based supramolecular hydrogels that are stimuli-responsive under aqueous conditions have many potential biological applications, including drug delivery and sensing. Herein, we reported a series of responsive peptide-based supramolecular hydrogels that respond to glutathione (GSH), nitric oxide (NO) and hydrogen sulfide (H2S), which are biologically important signaling molecules. The responsive hydrogelators were designed by "self-immolative" chemistry and constructed by using self-immolative groups to modify short peptides. The self-immolative capping group could be removed in the presence of a corresponding trigger, thus causing gel-sol phase transitions. The potential of our responsive hydrogels for drug release was also demonstrated in this study. Our study offered several candidates of responsive hydrogels for sensing and drug delivery.

7.
Arch Biochem Biophys ; 564: 184-8, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-25449062

ABSTRACT

CD4(+) T cell polarization plays a critical role in a number of immune disorders; the pathogenesis is unclear. Chromobox homolog 7 (Cbx7) is involved in the gene transcription of several cell types. This study aims to investigate the mechanism by which Cbx7 modulates the CD4(+) T cell polarization. Expression of Cbx7 was assessed by quantitative RT-PCR and Western blotting. Apoptosis of CD4(+) T cell was analyzed by flow cytometry. The FasL promoter methylation was evaluated by the methylation specific PCR. The results showed that CD4(+) CD25(-) T cells express Cbx7 that was increased significantly after activation by exposing to anti-CD3/CD28 Ab, but suppressed by exposing to specific antigens. More apoptotic cells were detected in CD4(+) T cells with the Cbx7 gene knockdown. Exposure to insulin-like growth factor-1 up regulated the expression of Cbx7 in CD4(+) T cells. After antigen-specific TCR activation, Cbx7-deficient CD4(+) T cells expressed more FasL and showed the FasL gene promoter hyper demethylation than wild CD4(+) T cells. In addition, CD4(+) T cells with overexpression of Cbx7 showed lower levels of FasL gene promoter demethylation. We conclude that CD4(+) T cells express Cbx7; the latter prevents FasL expression and the activation-induced CD4(+) T cell apoptosis.


Subject(s)
Apoptosis/physiology , CD4-Positive T-Lymphocytes/metabolism , Fas Ligand Protein/biosynthesis , Gene Expression Regulation/physiology , Lymphocyte Activation/physiology , Polycomb Repressive Complex 1/biosynthesis , Animals , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , DNA Methylation/physiology , Fas Ligand Protein/genetics , Fas Ligand Protein/immunology , Gene Knockdown Techniques , Insulin-Like Growth Factor I/genetics , Insulin-Like Growth Factor I/immunology , Insulin-Like Growth Factor I/metabolism , Male , Mice , Mice, Inbred BALB C , Polycomb Repressive Complex 1/genetics , Polycomb Repressive Complex 1/immunology , Promoter Regions, Genetic , Receptors, Antigen, T-Cell/genetics , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/physiology
SELECTION OF CITATIONS
SEARCH DETAIL
...