2. Academic Validation
  3. Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers

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

  • Sci Rep. 2018 Jan 18;8(1):1128. doi: 10.1038/s41598-018-19598-2.
Nobuyuki Morimoto 1,  Riho Takei 2,  Masaru Wakamura 2,  Yoshifumi Oishi 2,  Masafumi Nakayama 3,  Makoto Suzuki 2,  Masaya Yamamoto 2,  Françoise M Winnik 4 5 6
Affiliations

Affiliations

  • 1 Department of Materials Processing, Graduate School of Engineering, Tohoku University, 6-6-02 Aramaki-aza Aoba, Aoba-ku, Sendai, 980-8579, Japan. morimoto@material.tohoku.ac.jp.
  • 2 Department of Materials Processing, Graduate School of Engineering, Tohoku University, 6-6-02 Aramaki-aza Aoba, Aoba-ku, Sendai, 980-8579, Japan.
  • 3 Frontier Research Institute for Interdisciplinary Sciences (FRIS), Tohoku University, Aramaki aza Aoba 6-3, Aoba-ku, Sendai, 980-8578, Japan.
  • 4 Department of Chemistry, University of Montreal, CP6128 Succursale Center Ville, Montreal, QC, H3C 3J7, Canada. francoise.winnik@umontreal.ca.
  • 5 Department of Chemistry and Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland. francoise.winnik@umontreal.ca.
  • 6 Center for Materials Nanoarchitectonics, NIMS, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan. francoise.winnik@umontreal.ca.
PMID: 29348616 DOI: 10.1038/s41598-018-19598-2
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 (α or ω). 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 ω-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.

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