Jiménez-López, JuliaBravo-Caparrós, InmaculadaCabeza, LauraNieto, Francisco R.Ortiz, RaúlPerazzoli, GloriaFernández-Segura, EduardoCañizares, Francisco J.Baeyens, José M.Melguizo, ConsolaciónPrados, José2022-11-302022-11-302020-12-09Jiménez-López J, Bravo-Caparrós I, Cabeza L, Nieto FR, Ortiz R, Perazzoli G, et al. Paclitaxel antitumor effect improvement in lung cancer and prevention of the painful neuropathy using large pegylated cationic liposomes. Biomed Pharmacother. 2021 Jan;133:111059.0753-3322http://hdl.handle.net/10668/4432Paclitaxel (PTX), a drug widely used in lung cancer, has serious limitations including the development of peripheral neurotoxicity, which may lead to treatment discontinuation and therapy failure. The transport of PTX in large cationic liposomes could avoid this undesirable effect, improving the patient's prognosis. PTX was encapsulated in cationic liposomes with two different sizes, MLV (180-200 nm) and SUV (80-100 nm). In both cases, excellent biocompatibility and improved internalization and antitumor effect of PTX were observed in human and mice lung cancer cells in culture, multicellular spheroids and cancer stem cells (CSCs). In addition, both MLV and SUV with a polyethylene glycol (PEG) shell, induced a greater tumor volume reduction than PTX (56.4 % and 57.1 % vs. 36.7 %, respectively) in mice. Interestingly, MLV-PEG-PTX did not induce either mechanical or heat hypersensitivity whereas SUV-PEG-PTX produced a similar response to free PTX. Analysis of PTX distribution showed a very low concentration of the drug in the dorsal root ganglia (DRG) with MLV-PEG-PTX, but not with SUV-PEG-PTX or free PTX. These results support the hypothesis that PTX induces peripheral neuropathy by penetrating the endothelial fenestrations of the DRG (80-100 nm, measured in mice). In conclusion, our larger liposomes (MLV-PEG-PTX) not only showed biocompatibility, antitumor activity against CSCs, and in vitro and in vivo antitumor effect that improved PTX free activity, but also protected from PTX-induced painful peripheral neuropathy. These advantages could be used as a new strategy of lung cancer chemotherapy to increase the PTX activity and reduce its side effects.enAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Lung cancerPaclitaxelPegylated liposomesPeripheral neurotoxicityDorsal root gangliaLiposomesMulticellular tumor spheroidsPolyethylene glycolCancer stem cellsNeoplasias pulmonaresGanglios espinalesLiposomasEsferoides celularesPolietilenglicolesCélulas madre neoplásicasMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, PhytogenicMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell ProliferationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Technology, Pharmaceutical::Drug CompoundingMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::LipidsMedical Subject Headings::Chemicals and Drugs::Biomedical and Dental Materials::Membranes, Artificial::LiposomesMedical Subject Headings::Diseases::Respiratory Tract Diseases::Lung Diseases::Lung NeoplasmsMedical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred C57BLMedical Subject Headings::Anatomy::Cells::Stem Cells::Neoplastic Stem CellsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Alicyclic::Cycloparaffins::Cyclodecanes::Taxoids::PaclitaxelMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Physicochemical Phenomena::Particle SizeMedical Subject Headings::Diseases::Nervous System Diseases::Neuromuscular Diseases::Peripheral Nervous System DiseasesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Glycols::Ethylene Glycols::Polyethylene GlycolsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Tumor BurdenMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Spheroids, CellularMedical Subject Headings::Anatomy::Nervous System::Ganglia::Ganglia, Sensory::Ganglia, SpinalMedical Subject Headings::Phenomena and Processes::Biological Phenomena::Ecological and Environmental Phenomena::Environment::Atmosphere::Weather::Temperature::Hot TemperatureMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosisresearch article33378963Acceso abierto10.1016/j.biopha.2020.1110591950-6007