Membrane Translocation and Organelle-Selective Delivery Steered by Polymeric Zwitterionic Nanospheres

Nobuyuki Morimoto, Masaru Wakamura, Kanna Muramatsu, Sayaka Toita, Masafumi Nakayama, Wataru Shoji, Makoto Suzuki, Françoise M. Winnik

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The majority of nanoparticles designed for cellular delivery of drugs and imaging agents enter the cell via endocytotic pathways leading to their entrapment in endosomes that present a robust barrier to further trafficking of the nanoparticles within the cells. A few materials, such as the cell penetrating peptides (CPPs), are known to enter cells not only via endocytosis, but also via translocation through the cell membrane into the cytoplasm, successfully bypassing the endosomes. We report here that random copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate and poly(ethylene glycol) methacrylate, p(DMAPS-ran-PEGMA), are internalized in cells primarily via translocation through the cell membrane rather than endocytosis. The properties of the polymers and their modes of uptake were investigated systematically by dynamic light scattering, confocal fluorescence microscopy, and flow cytometry. Using specific inhibitors of the cellular uptake machinery in a human cervical carcinoma cell line (HeLa), we show that these nontoxic synthetic polyzwitterions exist in cell media as self-assembled nanospheres that unravel as they adsorb on the plasma membrane and translocate through it. Conjugates of p(DMAPS-ran-PEGMA) with rhodamine B were delivered selectively to the mitochondria, whereas doxorubicin (Dox)-p(DMAPS-ran-PEGMA) conjugates were accumulated in both the nucleus and the mitochondria, effectively inducing apoptosis in HeLa cells. These findings suggest that the noncytotoxic and readily synthesized p(DMAPS-ran-PEGMA) can find applications as bioimaging tools and drug nanocarriers.

Original languageEnglish
Pages (from-to)1523-1535
Number of pages13
JournalBiomacromolecules
Volume17
Issue number4
DOIs
Publication statusPublished - 2016 Apr 11

ASJC Scopus subject areas

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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  • Cite this

    Morimoto, N., Wakamura, M., Muramatsu, K., Toita, S., Nakayama, M., Shoji, W., Suzuki, M., & Winnik, F. M. (2016). Membrane Translocation and Organelle-Selective Delivery Steered by Polymeric Zwitterionic Nanospheres. Biomacromolecules, 17(4), 1523-1535. https://doi.org/10.1021/acs.biomac.6b00172