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Intracellular delivery enhancement of poly(amino acid) drug carriers by oligoarginine conjugation
Author(s) -
Yang Seung Rim,
Kim Seung Beom,
Joe Cheol O.,
Kim JongDuk
Publication year - 2008
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.31331
Subject(s) - endocytosis , internalization , intracellular , conjugated system , biophysics , liposome , conjugate , materials science , membrane , peptide , hela , cell membrane , pinocytosis , biochemistry , cell , polymer , chemistry , biology , nanotechnology , mathematical analysis , mathematics , composite material
Abstract Poly(2‐hydroxytethyl aspartamide) (PHEA) was effectively translocated in both fixed and unfixed HeLa cells, when oligoarginine (Arg 8 ) known as one of the cell‐penetrating peptides was conjugated via a thioether linkage. The internalization of PHEA‐Arg 8 into cells was a temperature‐dependent process, and the studies at endocytosis inhibition conditions suggested that an endocytosis was a key mechanism. The fluorescence spectra of PHEA‐Arg 8 in liposome solutions showed that PHEA‐Arg 8 was collectively adsorbed in the negative liposome membrane due to the high cationic property of a conjugated Arg 8 , representing that a surface adsorption was a first step in the internalization of PHEA‐Arg 8 . The membrane leakage activity of PHEA‐Arg 8 was much lower than that of Arg 8 own, meaning that PHEA‐Arg 8 does not effectively disrupt the cell membrane integrity. The uptake of polymer con„jugates increased with the incubation time and reached saturation after several hours. The increase in the number of „peptide conjugated to one polymer chain could increase the collective adsorption of polymer conjugates and enhance the cellular uptake. Thus, it is believed that PHEA‐Arg 8 could be internalized by an adsorptive‐endocytosis. A model conjugate of PHEA‐Arg 8 with methotrexate (PHEA‐MTX‐Arg 8 ) inhibited the cell proliferation about several orders of magnitude more active than PHEA‐MTX. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008