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Lipopeptide‐modified PEG‐PE‐based pharmaceutical nanocarriers for enhanced uptake in blood–brain barrier cells and improved cytotoxicity against glioma cells
Author(s) -
Sydow Karl,
Torchilin Vladimir P.,
Dathe Margitta
Publication year - 2014
Publication title -
european journal of lipid science and technology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.614
H-Index - 94
eISSN - 1438-9312
pISSN - 1438-7697
DOI - 10.1002/ejlt.201300373
Subject(s) - lipopeptide , nanocarriers , micelle , flow cytometry , in vivo , biophysics , chemistry , drug delivery , blood–brain barrier , cancer cell , cytotoxicity , glioma , peg ratio , peptide , in vitro , biochemistry , cancer research , microbiology and biotechnology , biology , cancer , bacteria , genetics , organic chemistry , neuroscience , finance , aqueous solution , economics , central nervous system
Surface modification of nanoparticles is a promising approach for enhancing the delivery of drugs into the brain and cancer cells. Recently cationic lipopeptide micelles showed selective uptake into endothelial cells of brain microvessels. Here, we show that lipopeptides are promising tools to deliver an anticancer drug incorporated into PEGylated lipid (PEG‐PE) micelles to brain endothelial cells and into glioblastoma cells. PEG‐PE micelles containing PCL were stably modified with different arginine (R‐) and lysine (K)‐rich lipopeptides. The size and surface charge of the micelles did not change after modification with lipopeptides. Flow cytometry (FACS) and confocal laser scanning microscopy (CLSM) revealed pronounced interaction of lipopeptide‐modified micelles with brain endothelial cells. Furthermore, the co‐localisation of both the fluorescent lipopeptides and a marker lipid of micelles within human glioblastoma cells (U87MG) confirmed the integrity of the carrier after internalisation. FACS studies showed that the arginine‐rich lipopeptide caused most efficient uptake into the cancer cells. The pronounced uptake correlated with higher a cytotoxic effect of PCL incorporated into peptide‐tagged micelles compared to the unmodified carriers. As a conclusion, arginine‐rich lipopeptides known to enhance the uptake of different NP into blood–brain barrier endothelial cells seem to be also encouraging candidates for targeting brain‐located tumors. Practical applications: The surface modification of existing carrier systems with lipopeptides to improve their applicability has been proven by this work. Furthermore, the findings in this study are the basis for further improvement of lipopeptide modified PEG‐PE micelles and their possible in vivo application in animal models of glioblastoma. The incorporation of anti‐cancer drugs as well as diagnostic agents and their delivery to and beyond the BBB can be a tool for a broad number of further investigations. Lipopeptide (P2Rn)‐modified PEG‐PE micelles show enhanced uptake into human glioma cells (nuclei stained cyan). This improved uptake correlates with higher cytotoxicity of incorporated anti‐cancer drug paclitaxel (PCL).