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1.
Theranostics ; 11(14): 7005-7017, 2021.
Article in English | MEDLINE | ID: covidwho-1524524

ABSTRACT

The tumor suppressor protein p53 remains in a wild type but inactive form in ~50% of all human cancers. Thus, activating it becomes an attractive approach for targeted cancer therapies. In this regard, our lab has previously discovered a small molecule, Inauhzin (INZ), as a potent p53 activator with no genotoxicity. Method: To improve its efficacy and bioavailability, here we employed nanoparticle encapsulation, making INZ-C, an analog of INZ, to nanoparticle-encapsulated INZ-C (n-INZ-C). Results: This approach significantly improved p53 activation and inhibition of lung and colorectal cancer cell growth by n-INZ-C in vitro and in vivo while it displayed a minimal effect on normal human Wi38 and mouse MEF cells. The improved activity was further corroborated with the enhanced cellular uptake observed in cancer cells and minimal cellular uptake observed in normal cells. In vivo pharmacokinetic evaluation of these nanoparticles showed that the nanoparticle encapsulation prolongates the half-life of INZ-C from 2.5 h to 5 h in mice. Conclusions: These results demonstrate that we have established a nanoparticle system that could enhance the bioavailability and efficacy of INZ-C as a potential anti-cancer therapeutic.


Subject(s)
Antineoplastic Agents/pharmacology , Colorectal Neoplasms/drug therapy , Indoles/pharmacology , Lung Neoplasms/drug therapy , Nanoparticles/chemistry , Phenothiazines/pharmacology , Tumor Suppressor Protein p53/metabolism , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Biological Availability , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Humans , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/therapeutic use , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Nanoparticles/toxicity , Nanoparticles/ultrastructure , Phenothiazines/chemistry , Phenothiazines/pharmacokinetics , Phenothiazines/therapeutic use , Spectroscopy, Fourier Transform Infrared , Tumor Suppressor Protein p53/genetics , Xenograft Model Antitumor Assays
2.
J Am Chem Soc ; 143(43): 17891-17909, 2021 11 03.
Article in English | MEDLINE | ID: covidwho-1483091

ABSTRACT

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.


Subject(s)
Anti-Infective Agents/chemistry , Drug Design , Phototherapy/methods , Animals , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Bacteria/drug effects , Biofilms/drug effects , Biofilms/radiation effects , Coloring Agents/chemistry , Coloring Agents/pharmacology , Equipment and Supplies/microbiology , Equipment and Supplies/virology , Escherichia coli/drug effects , Escherichia coli/physiology , Eye Diseases/drug therapy , Eye Diseases/pathology , Fungi/drug effects , Graphite/chemistry , Light , Nanoparticles/chemistry , Nanoparticles/toxicity , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Quantum Theory , Reactive Oxygen Species/metabolism , Viruses/drug effects
3.
Adv Healthc Mater ; 10(6): e2001433, 2021 03.
Article in English | MEDLINE | ID: covidwho-1046877

ABSTRACT

The ongoing pandemic of the coronavirus disease (Covid-19), caused by the spread of the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), highlights the need for broad-spectrum antiviral drugs. In this Essay, it is argued that such agents already exist and are readily available while highlighting the challenges that remain to translate them into the clinic. Multivalent inhibitors of viral infectivity based on polymers or supramolecular agents and nanoparticles are shown to be broadly acting against diverse pathogens in vitro as well as in vivo. Furthermore, uniquely, such agents can be virucidal. Polymers and nanoparticles are stable, do not require cold chain of transportation and storage, and can be obtained on large scale. Specifically, for the treatment of respiratory viruses and pulmonary diseases, these agents can be administered via inhalation/nebulization, as is currently investigated in clinical trials as a treatment against SARS CoV-2/Covid-19. It is believed that with due optimization and clinical validation, multivalent inhibitors of viral infectivity can claim their rightful position as broad-spectrum antiviral agents.


Subject(s)
Antiviral Agents/therapeutic use , Virus Diseases/drug therapy , Antibodies, Neutralizing/therapeutic use , Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Humans , Nanoparticles/chemistry , Nanoparticles/toxicity , Polymers/chemistry , Polymers/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Virus Internalization/drug effects
4.
Mater Sci Eng C Mater Biol Appl ; 112: 110924, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1017020

ABSTRACT

Research on highly effective antiviral drugs is essential for preventing the spread of infections and reducing losses. Recently, many functional nanoparticles have been shown to possess remarkable antiviral ability, such as quantum dots, gold and silver nanoparticles, nanoclusters, carbon dots, graphene oxide, silicon materials, polymers and dendrimers. Despite their difference in antiviral mechanism and inhibition efficacy, these functional nanoparticles-based structures have unique features as potential antiviral candidates. In this topical review, we highlight the antiviral efficacy and mechanism of these nanoparticles. Specifically, we introduce various methods for analyzing the viricidal activity of functional nanoparticles and the latest advances in antiviral functional nanoparticles. Furthermore, we systematically describe the advantages and disadvantages of these functional nanoparticles in viricidal applications. Finally, we discuss the challenges and prospects of antiviral nanostructures. This topic review covers 132 papers and will enrich our knowledge about the antiviral efficacy and mechanism of various functional nanoparticles.


Subject(s)
Antiviral Agents/chemistry , Nanoparticles/chemistry , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , DNA Viruses/drug effects , DNA Viruses/physiology , Graphite/chemistry , Metal Nanoparticles/chemistry , Metal Nanoparticles/toxicity , Nanoparticles/therapeutic use , Nanoparticles/toxicity , Polymers/chemistry , Quantum Dots/chemistry , Quantum Dots/therapeutic use , Quantum Dots/toxicity , Zika Virus/drug effects , Zika Virus Infection/drug therapy , Zika Virus Infection/veterinary
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