Nonviral delivery systems are relatively easy to produce in the large scale, are safe, and elicit a negligible immune response. Nanoparticles (NPs) offer promise as nonviral vectors as biocompatible and -degradable carriers of drugs with targeting to specific sites by surface receptors of monoclonal antibodies (mAbs). We investigated the effect of four PEG-PLGA (polyethylene glycol-polylactic-co-glycolic acid) NP systems on drug-resistant B-chronic lymphocytic leukemia (B-CLL) cells in vitro, three of them encapsulating the drug, hydroxylchloroquine (HDQ), two with NP surface coatings of mAbs (NP1) CD20, (NP2) CD19, and CD20, and one (NP3) with no mAb, but tagged with the fluorescent marker, fluorescein isothiocyanate. The fourth NP system (NP4) was coated with anti-CD19/FITC and anti-CD20/Alexa-Fluor((R)) antibodies, but did not contain the active drug, HCQ. Our data indicate that PEG-PLGA nanoparticles with surface mAbs are suitable for selective drug delivery to B-CLL cells and produce a strong apoptotic effect when loaded with the lysosomotropic agent, HDQ.
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http://dx.doi.org/10.1089/cbr.2009.0655 | DOI Listing |
Virology
January 2025
Institute of Immunology, Philipps-Universität Marburg, 35043, Marburg, Germany; CSL Innovation GmbH, Emil-von-Behring, Straße 76, 35041, Marburg, Germany.
Cationic lysosomotropic molecules such as ammonium salts and chloroquine inhibit influenza A virus (IAV) infection in cell culture by counteracting endosomal acidification and hampering viral-endosomal fusion. Here, we studied the effects of storage of L-glutamine-supplemented cell culture media on accumulation of ammonium and inhibition of IAV infection. The storage-related inhibitory effect was observed for DMEM and OptiMEM media but not for RPMI medium, and was more pronounced for IAV with pH-stable hemagglutinin.
View Article and Find Full Text PDFEur J Med Chem
December 2024
Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, 226-8501, Japan; School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan. Electronic address:
We have discovered lysosomotropic autophagy inhibitors from our compound library of sp-rich diazatricycloundecane skeletons. Compound 1u was identified as the most potent biological activity for LC3-II protein accumulation through the structure-activity relationships (SARs) for LC3-II protein accumulation and anti-proliferative activity at the three freely available substituents (R-R) in the diazatricycloundecane skeleton. Compound 1u inhibited lysosome-dependent degradation without affecting autophagosome formation.
View Article and Find Full Text PDFToxicol In Vitro
December 2024
College of Animal Science and Technology, Yangtze University, Jingzhou 434025, Hubei, China. Electronic address:
Chloroquine (CQ) is widely used in the therapy against malarial, tumor and recently the COVID-19 pandemic, as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway. We previously reported that CQ (20 μM, 36 h) could reprogram transcriptome, and impair multiple signaling pathways vital to porcine immature Sertoli cells (iSCs). However, whether CQ treatment could affect the metabolomic compositions of porcine iSCs remains unclear.
View Article and Find Full Text PDFChem Sci
August 2024
Centre for Cancer Cell Biology and Drug Discovery, Griffith University Nathan Brisbane 4111 Queensland Australia
Innovative -acridine thiosemicarbazones (NATs) were designed along with their iron(iii), copper(ii), and zinc(ii) complexes. Lysosomal targeting was promoted by specifically incorporating the lysosomotropic Pgp substrate, acridine, into the thiosemicarbazone scaffold to maintain the tridentate N, N, S-donor system. The acridine moiety enables a significant advance in thiosemicarbazone design, since: (1) it enables tracking of the drugs by confocal microscopy using its inherent fluorescence; (2) it is lysosomotropic enabling lysosomal targeting; and (3) as acridine is a P-glycoprotein (Pgp) substrate, it facilitates lysosomal targeting, resulting in the drug overcoming Pgp-mediated resistance.
View Article and Find Full Text PDFACS Sens
August 2024
Department of Chemistry, Yonsei University, Seoul 03722, Republic of Korea.
Owing to the biological significance of Cl in cells, several chemical fluorescent probes and biosensors have been constructed to monitor this anion in the cytosol and subcellular organelles. However, a fluorescent probe for the selective detection of nuclear Cl has not been described thus far. In the current study, we developed the first nuclear Cl-selective biosensor, Cl-YFP-NLS, whose fluorescence was effectively quenched by this anion, and demonstrated that it is an efficient and powerful tool for determining the levels of nuclear Cl.
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