RT Journal Article
T1 Paclitaxel antitumor effect improvement in lung cancer and prevention of the painful neuropathy using large pegylated cationic liposomes
A1 Jiménez-López, Julia
A1 Bravo-Caparrós, Inmaculada
A1 Cabeza, Laura
A1 Nieto, Francisco R.
A1 Ortiz, Raúl
A1 Perazzoli, Gloria
A1 Fernández-Segura, Eduardo
A1 Cañizares, Francisco J.
A1 Baeyens, José M.
A1 Melguizo, Consolación
A1 Prados, José
K1 Lung cancer
K1 Paclitaxel
K1 Pegylated liposomes
K1 Peripheral neurotoxicity
K1 Dorsal root ganglia
K1 Liposomes
K1 Multicellular tumor spheroids
K1 Polyethylene glycol
K1 Cancer stem cells
K1 Neoplasias pulmonares
K1 Ganglios espinales
K1 Liposomas
K1 Esferoides celulares
K1 Polietilenglicoles
K1 Células madre neoplásicas
AB Paclitaxel (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.
PB Elsevier Masson SAS
SN 0753-3322
YR 2020
FD 2020-12-09
LK http://hdl.handle.net/10668/4432
UL http://hdl.handle.net/10668/4432
LA en
NO Jiménez-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.
DS RISalud
RD Apr 7, 2025