Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.
Understanding the interplay between nanoparticles (NPs) and cells is essential to designing more efficient nanomedicines. Previous research has shown the role of the cell cycle having impact on the efficiency of cellular uptake and accumulation of NPs. However, there is a limited investigation into the biological fate of NPs in cells that are permanently withdrawn from the cell cycle. Here we utilize senescent WI-38 fibroblasts, which do not divide and provide a definitive model for tracking the biological fate of silica nanoparticles (SiNPs) independent of cell cycle. We use several methods to measure the cellular uptake kinetics and intracellular retention of SiNPs, including confocal laser scanning microscopy (CLSM), flow cytometry, and transmission electron microscopy (TEM). We demonstrate that SiNPs readily enter into senescent cells. Once internalized, SiNPs do not exit and accumulate in the cytoplasm for long term. Our study provides a basis for future development of NP-based tools that can detect and target senescent cells for therapy.
Wpłynęło w lutym, zaakceptowano w październiku 2020 r.Streszczenie: Owadobójcze właściwości Bacillus thuringiensis (Bt) sprawiają, że jest to cenny gatunek bakterii dla rozwoju rolnictwa. Produkowane przez Bt białka Cry i Cyt działają w sposób selektywny, dlatego ich stosowanie prowadzi do wyeliminowania tylko larw owadów docelowych. Znane są również inne substancje produkowane przez bakterie Bt, które mogą się przyczynić do eliminacji agrofagów i promowania wzrostu roślin. Ponadto podejmowane są próby stosowania szczepów B. thuringiensis w procesie bioremediacji terenów skażonych toksycznymi związkami organicznymi oraz w medycynie, w zwalczaniu patogenów ludzkich i zwierzęcych oraz komórek nowotworowych.1. Wprowadzenie. 2. Charakterystyka gatunku Bacillus thuringiensis. 3. Czynniki wirulencji Bacillus thuringiensis. 4. Wykorzystanie Bacil lus thuringiensis w nowoczesnym rolnictwie 5. Nowe możliwości wykorzystania bakterii Bacillus thuringiensis. 6. Podsumowanie
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