Fast and effective mitochondrial delivery of omega-Rhodamine-B-polysulfobetaine-PEG copolymers

Show full item record



Permalink

http://hdl.handle.net/10138/231871

Citation

Morimoto , N , Takei , R , Wakamura , M , Oishi , Y , Nakayama , M , Suzuki , M , Yamamoto , M & Winnik , F M 2018 , ' Fast and effective mitochondrial delivery of omega-Rhodamine-B-polysulfobetaine-PEG copolymers ' , Scientific Reports , vol. 8 , 1128 . https://doi.org/10.1038/s41598-018-19598-2

Title: Fast and effective mitochondrial delivery of omega-Rhodamine-B-polysulfobetaine-PEG copolymers
Author: Morimoto, Nobuyuki; Takei, Riho; Wakamura, Masaru; Oishi, Yoshifumi; Nakayama, Masafumi; Suzuki, Makoto; Yamamoto, Masaya; Winnik, Francoise M.
Other contributor: University of Helsinki, Department of Chemistry


Date: 2018-01-18
Language: eng
Number of pages: 10
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-018-19598-2
URI: http://hdl.handle.net/10138/231871
Abstract: Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 <M-n <74.0 kg/mol) with two different endgroups. We labeled them with Rho groups attached along the chain or on one of the two endgroups (alpha or omega). From studies by flow cytometry and confocal fluorescence microscopy of the copolymers internalization in HeLa cells in the absence and presence of pharmacological inhibitors, we established that the polymers cross the cell membrane foremost by translocation and also by endocytosis, primarily clathrin-dependent endocytosis. The most effective mitochondrial entry was achieved by copolymers of M-n <30.0 kg/mol, lightly grafted with PEG chains (<5 mol %) labeled with Rho in the omega-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.
Subject: ARGININE-RICH PEPTIDES
LIPOSOME-BASED CARRIER
CELLULAR UPTAKE
DRUG-DELIVERY
MITO-PORTER
IN-VITRO
MEMBRANE
CHOLESTEROL
CELLS
TRANSLOCATION
116 Chemical sciences
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
s41598_018_19598_2.pdf 2.541Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record