ArticleCells2020
The Lysosomotropic Activity of Hydrophobic Weak Base Drugs is Mediated via Their Intercalation into the Lysosomal Membrane.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Cepharanthine inhibits lysosomes and induces apoptosis in triple‑negative breast cancer cells.Molecular medicine reports · 2026Article
- Improving the Estimation of pThe journal of physical chemistry. B · 2026Article
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- Lysosome as a Chemical Reactor.International journal of molecular sciences · 2025Review
- Epidrug screening identifies type I PRMT inhibitors as modulators of lysosomal exocytosis and drug sensitivity in cancers.Cell death & disease · 2025Article
- Adding the AMBER 14SB Force Field to the Stochastic Titration CpHMD Method.Journal of chemical theory and computation · 2025Article
- Endosomal disruption by co-encapsulating gentamicin in lipid nanoparticles for efficient siRNA delivery and cancer therapy.Asian journal of pharmaceutical sciences · 2025Article
- Acidic sphingomyelinase interactions with lysosomal membranes and cation amphiphilic drugs: A molecular dynamics investigation.Computational and structural biotechnology journal · 2024Article
- High Charge Density in Peptide Dendrimers is Required to Destabilize Membranes: Insights into Endosome Evasion.Journal of chemical information and modeling · 2024Article
- Review
- Weak base drug-induced endolysosome iron dyshomeostasis controls the generation of reactive oxygen species, mitochondrial depolarization, and cytotoxicity.NeuroImmune pharmacology and therapeutics · 2024Article
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Carboranyl-1,8-naphthalimide intercalators induce lysosomal membrane permeabilization and ferroptosis in cancer cell lines.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Arginine Residues Modulate the Membrane Interactions of pHLIP Peptides.Journal of chemical information and modeling · 2023Article
- Recent Development of Advanced Fluorescent Molecular Probes for Organelle-Targeted Cell Imaging.Biosensors · 2023Review
- Recent advances on molecular dynamics-based techniques to address drug membrane permeability with atomistic detail.BBA advances · 2023Article
- Article
- Increasing the Realism ofJournal of chemical theory and computation · 2022Article
- Amantadine: reappraisal of the timeless diamond-target updates and novel therapeutic potentials.Journal of neural transmission (Vienna, Austria : 1996) · 2021Review
- Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance.Cancer cell international · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipophilic weak base therapeutic agents, termed lysosomotropic drugs (LDs), undergo marked sequestration and concentration within lysosomes, hence altering lysosomal functions. This lysosomal drug entrapment has been described as luminal drug compartmentalization. Consistent with our recent finding that LDs inflict a pH-dependent membrane fluidization, we herein demonstrate that LDs undergo intercalation and concentration within lysosomal membranes. The latter was revealed experimentally and computationally by (a) confocal microscopy of fluorescent compounds and drugs within lysosomal membranes, and (b) molecular dynamics modeling of the pH-dependent membrane insertion and accumulation of an assortment of LDs, including anticancer drugs. Based on the multiple functions of the lysosome as a central nutrient sensory hub and a degradation center, we discuss the molecular mechanisms underlying the alteration of morphology and impairment of lysosomal functions as consequences of LDs' intercalation into lysosomes. Our findings bear important implications for drug design, drug induced lysosomal damage, diseases and pertaining therapeutics.
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