RESUMO
Single-cell metabolomics (SCMs) is a powerful tool for studying cellular heterogeneity by providing insight into the differences between individual cells. With the development of a set of promising SCMs pipelines, this maturing technology is expected to be widely used in biomedical research. However, before SCMs is ready for primetime, there are some challenges to overcome. In this review, we summarize the trends and challenges in the development of SCMs. We also highlight the latest methodologies, applications, and sketch the perspective for integration with other omics and imaging approaches.
Assuntos
Metabolômica , Análise de Célula Única , Análise de Célula Única/métodos , Espectrometria de Massas/métodos , Metabolômica/métodosRESUMO
The major challenge in the field of antibacterial agents is to overcome the low-permeability of bacteria cell membranes that protects the cells against diverse drugs. In this work, water-soluble polyaniline (PANI)-poly (p-styrenesulfonic acid) (PSS) (PANI:PSS) is found to spontaneously penetrate bacteria cellular membranes in a non-disruptive way, leaving no evidence of membrane poration/disturbance or cell death, thus avoiding side effects caused by cationic ammonia groups in traditional ammonia-containing antibacterial agents. For aqueous synthesis, which is important for biocompatibility, the polymer is synthesized via an enzyme-mimetic route relying on the catalysis of a nanozyme. Owing to its fluorescent properties, the localization of as-prepared PANI:PSS is determined by the confocal microscope, and the results confirm its rapid entry into bacteria. Under 808 nm near-infrared (NIR) irradiation, the internalized PANI:PSS generates local hyperthermia and destroys bacteria highly efficiently from inside the cells due to its excellent photothermal effects. Staphylococcus aureus (S. aureus), M ethicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) could be effectively eliminated as well as the corresponding bacterial biofilms. Results of in vivo antibacterial experiments demonstrate excellent antibacterial activities of the water-soluble PANI:PSS without side effects. Therefore, the prepared water-soluble polymer in this study has great potential in the treatment of various bacterial infections.
RESUMO
Copper-containing antimicrobials are highly valuable in the field of medical disinfectants owing to their well-known high antimicrobial efficacy. Artificially synthesized nanozymes which can increase the level of reactive oxygen species (ROS) in the bacterial system have become research hotspots. Herein, we describe the design and fabrication of degradable Cu-doped phosphate-based glass (Cu-PBG) nanozyme, which can achieve excellent antibacterial effects against Gram-positive and Gram-negative bacteria. The antibacterial mechanism is based on the generation of ROS storm and the release of copper. It behaves like a peroxidase in wounds which are acidic and exerts lethal oxidative stress on bacteria via catalyzing the decomposition of H2O2 into hydroxyl radicals (â¢OH). Quite different from any other reported nanozymes, the Cu-PBG is intrinsically degradable due to its phosphate glass nature. It gradually degrades and releases copper ions in a physiological environment, which further enhances the inhibition efficiency. Satisfactory antibacterial effects are verified both in vitro and in vivo. Being biodegradable, the prepared Cu-PBG exhibits excellent in vivo biocompatibility and does not cause any adverse effects caused by its long-time residence time in living organisms. Collectively, these results indicate that the Cu-PBG nanozyme could be used as an efficient copper-containing antimicrobial with great potential for clinical translation.
Assuntos
Antibacterianos/química , Cobre/química , Desinfetantes/química , Vidro/química , Nanoestruturas/química , Fosfatos/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Catálise , Cobre/farmacologia , Desinfetantes/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Infecções por Escherichia coli/prevenção & controle , Humanos , Peróxido de Hidrogênio/metabolismo , Fosfatos/farmacologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologiaRESUMO
With the emergence of drug-resistant bacteria, conventional antibiotics are becoming increasingly ineffective for the treatment of bacterial infections. Nanomaterial-modified antibiotics, denoted as "nanoantibiotics", can usually circumvent most of the shortcomings of conventional antibiotics, thus improving antibacterial activities. Here, we developed triclosan-based supramolecular hydrogel nanoantibiotics by conjugating small molecule antibiotic triclosan (TCS) to self-assembling peptides. The resultant nanoantibiotics presented many beneficial characteristics: (i) a stable three-dimensional nanofiber structure; (ii) increased TCS solubility by 850-fold; (iii) acid-responsive TCS release; (iv) favorable biocompatibility. In consequence, the nanoantibiotics showed potent in vitro broad-spectrum antibacterial activities against both Gram-positive and Gram-negative bacteria based on the cooperative effect of antibiotic TCS and the nanostructure-induced bacterial membrane disruption. Furthermore, the TCS-based supramolecular hydrogel nanoantibiotics exhibited enhanced antibacterial activities with low side effects, according to the in vivo antibacterial evaluation at the macro and micro level. Therefore, the simple and effective hydrogel nanoantibiotics developed here hold great potential for the treatment of intractable bacterial infections.
Assuntos
Antibacterianos , Triclosan , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , HidrogéisRESUMO
Noninvasive multimodality imaging-guided precision photothermal therapy (PTT) is proven to be an effective strategy for tumor theranostics by integrating diagnostics and therapeutics in one nanoplatform. In this study, indocyanine green (ICG)-conjugated and radionuclide iodine-125 (125 I)-labeled polymeric micelles (PEG-PTyr(125 I)-ICG PMs) are strategically prepared by the self-assembly of the ICG-decorated amphiphilic diblock polymer poly(ethylene glycol)-poly(l-tyrosine-125 I)-(indocyanine green) (PEG-PTyr(125 I)-ICG). The as-prepared polymeric micelles exhibit favorable biocompatibility, excellent size/photo/radiolabel stability, a high-photothermal conversion efficiency, a passive tumor-targeting ability, and a fluorescence (FL)/photoacoustic (PA)/single photon emission computed tomography (SPECT) imaging property. After tail intravenous injection, the polymeric micelles can efficiently accumulate at the tumor site and present comprehensive FL/PA/SPECT images with a high sensitivity, excellent spatial resolution, and unlimited tissue penetration under near-infrared (NIR) irradiation. Upon 808 nm laser irradiation, the subsequent precision PTT of tumors can be achieved with minimal cumulative side effects. Thus, this capable multifunctional nanoplatform with simple components and preparation procedures for FL/PA/SPECT multimodality imaging-guided PTT can be a potential candidate for clinical tumor theranostics.
Assuntos
Verde de Indocianina , Neoplasias , Contenção de Riscos Biológicos , Humanos , Radioisótopos do Iodo , Micelas , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , Polímeros , Nanomedicina TeranósticaRESUMO
Nowadays, how to improve the selectivity of chemotherapy drugs and reduce their side effects is still a significant challenge for cancer research. Although enzyme-instructed self-assembly (EISA) has provided a promising approach for selective cancer therapy, the application of EISA is still suffering from requiring much higher concentrations for inhibiting cancer cells. Therefore, new strategies are needed to maximize the anticancer efficacy and preserve the selectivity of EISA. In this study, we rationally designed and synthesised a novel peptide-based prodrug molecule, NapGDFDFpYSV, combining EISA with the YSV anticancer peptide. The activity of the prodrug molecule was remarkably reduced by masking "Y" with a phosphoryl (-PO3) group and was recovered through dephosphorylation in situ by alkaline phosphatase (ALP) catalysis. The resulting monomer, NapGDFDFYSV, as a hydrogelator further self-assembled into the nanodrug on the cell surface, resulting in enhanced cellular uptake and selective high cytotoxicity to cells overexpressing ALP via action on histone deacetylase. Moreover, the required cell inhibition concentration of NapGDFDFpYSV was much lower than its critical micelle concentration (CMC), exhibiting outstanding advantages compared with separately used EISA without the anticancer peptide. Our study provides a new strategy to improve the cytotoxicity selectivity and bioactivity of chemotherapy drugs as well as the anticancer efficiency of EISA.
Assuntos
Antineoplásicos/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Camundongos , Estrutura Molecular , Células Tumorais CultivadasRESUMO
Supramolecular hydrogels of self-assembling peptide-drug conjugates have been considered as effective self-delivery drug systems for cancer therapy in recent years. Here, a novel self-assembling peptide-based supramolecular hydrogel was developed by simultaneously conjugating small-molecule drug chlorambucil (CRB) and peptide drug tyroservatide (YSV) to the self-assembling peptide. The resulting hydrogel with a nanofiber structure showed enhanced stability against proteinase K degradation and an improved cellular uptake performance in comparison with the free molecules. As a consequence, it exhibited enhanced antitumor efficiency both in vitro and in vivo with favorable biocompatibility. This biocompatible self-delivery drug system could not only significantly improve the delivery efficiency of the small-molecule drugs but also adequately synergize the antitumor effect of CRB and YSV, inspiring the design of new strategies of cancer combination therapy.