{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Simon-Gracia L"],"funding":["Eesti Teadusagentuur","H2020 Marie Sklodowska-Curie Actions","EuroNanoMed III","Division of Materials Research","Ministerio de Ciencia e Innovaci?n","National Institute of General Medical Sciences","NIGMS NIH HHS","European Regional Development Fund"],"pagination":["56613-56622"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9879205"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(51)"],"pubmed_abstract":["Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLs<sub>PTX</sub>) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLs<sub>PTX</sub> and PTX-containing fluid lipid nanodiscs (nanodiscs<sub>PTX</sub>). These CLs<sub>PTX</sub> and nanodiscs<sub>PTX</sub> show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol % PEG-lipid). Here, we studied the PTX loading, <i>in vivo</i> circulation half-life, and biodistribution of systemically administered CLs<sub>PTX</sub> and nanodiscs<sub>PTX</sub> and assessed their ability to induce apoptosis in triple-negative breast-cancer-bearing immunocompetent mice. We focused on <i>fluid</i> rather than <i>solid</i> lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol % of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLs<sub>PTX</sub> and nanodiscs<sub>PTX</sub> was able to incorporate up to 2.5 mol % PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol % PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol % (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration, and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy."],"journal":["ACS applied materials & interfaces"],"pubmed_title":["Paclitaxel-Loaded Cationic Fluid Lipid Nanodiscs and Liposomes with Brush-Conformation PEG Chains Penetrate Breast Tumors and Trigger Caspase-3 Activation."],"pmcid":["PMC9879205"],"funding_grant_id":["R01GM130769","PRG230","2014-2020.4.01.15-0012","DMR-1807327","R01 GM130769","EAG79","PSG38","RYC2020-028754-I","MOBJD11","PID2021-122364OA-I00"],"pubmed_authors":["Ewert KK","Steffes VM","Safinya CR","Simon-Gracia L","Sidorenko V","Teesalu T","Scodeller P","Fisher WS"],"additional_accession":[]},"is_claimable":false,"name":"Paclitaxel-Loaded Cationic Fluid Lipid Nanodiscs and Liposomes with Brush-Conformation PEG Chains Penetrate Breast Tumors and Trigger Caspase-3 Activation.","description":"Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLs<sub>PTX</sub>) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLs<sub>PTX</sub> and PTX-containing fluid lipid nanodiscs (nanodiscs<sub>PTX</sub>). These CLs<sub>PTX</sub> and nanodiscs<sub>PTX</sub> show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol % PEG-lipid). Here, we studied the PTX loading, <i>in vivo</i> circulation half-life, and biodistribution of systemically administered CLs<sub>PTX</sub> and nanodiscs<sub>PTX</sub> and assessed their ability to induce apoptosis in triple-negative breast-cancer-bearing immunocompetent mice. We focused on <i>fluid</i> rather than <i>solid</i> lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol % of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLs<sub>PTX</sub> and nanodiscs<sub>PTX</sub> was able to incorporate up to 2.5 mol % PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol % PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol % (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration, and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-03-18T14:09:24.058Z","creation":"2025-04-06T12:27:59.231Z"},"accession":"S-EPMC9879205","cross_references":{"pubmed":["36521233"],"doi":["10.1021/acsami.2c17961"]}}