PEGylation of Paclitaxel-Loaded Cationic Liposomes Drives Steric Stabilization of Bicelles and Vesicles thereby Enhancing Delivery and Cytotoxicity to Human Cancer Cells
| Autor: | Cyrus R. Safinya, Clinton S. Potter, Scott MacDonald, Victoria M. Steffes, Bridget Carragher, Kai K. Ewert, John H. Crowe, Zhening Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
Materials science
Paclitaxel paclitaxel delivery Bioengineering 02 engineering and technology cationic liposomes Micelle Article Polyethylene Glycols 03 medical and health sciences 0302 clinical medicine Engineering Neoplasms PEG ratio discoidal micelles Humans Nanotechnology General Materials Science Cationic liposome Nanoscience & Nanotechnology Cytotoxicity Cancer cryogenic electron microscopy bicelles Vesicle technology industry and agriculture PEGylation 021001 nanoscience & nanotechnology 030220 oncology & carcinogenesis Delayed-Action Preparations Drug delivery Liposomes PC-3 Cells Chemical Sciences Biophysics 0210 nano-technology Drug carrier |
| Zdroj: | ACS applied materials & interfaces, vol 12, iss 1 ACS Appl Mater Interfaces |
| Popis: | Poly(ethylene glycol) (PEG) is a polymer used widely in drug delivery to create "stealth" nanoparticles (NPs); PEG coatings suppress NP detection and clearance by the immune system and beneficially increase NP circulation time in vivo. However, NP PEGylation typically obstructs cell attachment and uptake in vitro compared to the uncoated equivalent. Here, we report on a cationic liposome (CL) NP system loaded with the hydrophobic cancer drug paclitaxel (PTX) in which PEGylation (i.e., PEG-CLPTX NPs) unexpectedly enhances, rather than diminishes, delivery efficacy and cytotoxicity to human cancer cells. This highly unexpected enhancement occurs even when the PEG-chains coating the NP are in the transition regime between the mushroom and brush conformations. Cryogenic transmission electron microscopy (TEM) of PEG-CLPTX NPs shows that PEG causes the proliferation of a mixture of sterically stabilized nanometer-scale vesicles and anisotropic micelles (e.g., bicelles). Remarkably, the onset of bicelles at sub-monolayer concentrations of the PEG coat has to our knowledge not been previously reported; it was previously thought that PEG-lipid in this composition regime was incorporated into vesicles but did not alter their shape. Confocal microscopy and flow cytometry reveal significantly greater PTX cell uptake from stabilized PEG-CLPTX NPs (vesicles and bicelles) in contrast to bare CLPTX NPs, which can aggregate in cell medium. This underscores the ability of steric stabilization to facilitate NP entry into cells via distinct size-dependent endocytic pathways, some of which cannot transport large NP aggregates into cells. This study highlights the value of understanding how PEGylation alters NP shape and structure, and thus NP efficacy, to design next-generation stealth drug carriers that integrate active cell-targeting strategies into NPs for in vivo delivery. |
| Databáze: | OpenAIRE |
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