Internalization Mechanisms of Pyridinium Sulfobetaine Polymers Evaluated by Induced Protic Perturbations on Cell Surfaces

Tatsuro Goda, Hiroaki Hatano, Masaya Yamamoto, Yuji Miyahara, Nobuyuki Morimoto

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Understanding the interactions of soft nanomatters with cell membranes is particularly important for research into nanocarrier-based drug delivery systems, cell engineering, and subcellular imaging. Most nanoparticles, vesicles, micelles, and polymeric aggregates are internalized into endosomes and, eventually, lysosomes in the cytosol because of energy-dependent endocytic processes. Endocytic uptake substantially limits the access to the cytoplasm where a cargo agent acts. Bypassing the endocytic pathways by direct penetration into plasma membrane barriers would enhance the efficacy of nanomedicines. Some zwitterionic polymer nanoaggregates have been shown to permeate into the cell interior in an energy-independent manner. We have elucidated this phenomenon by observing changes in the biomembrane barrier functions against protons as the smallest indicator and have used these results to further design and develop poly(betaines). In this work, we investigated the translocation mechanisms for a series of zwitterionic poly(methacrylamide) and poly(methacrylate) species bearing a pyridinium propane sulfonate moiety in the monomers. Minor differences in the monomer structures and functional groups were observed to have dramatic effects on the interaction with plasma membranes during translocation. The ability to cross the plasma membrane involves a balance among the betaine dipole-dipole interaction, NH-πinteraction, π-πinteraction, cation-πinteraction, and amide hydrogen bonding. We found that the cell-penetrating polysulfobetaines had limited or no detrimental effect on cell proliferation. Our findings enhance the opportunity to design and synthesize soft nanomatters for cell manipulations by passing across biomembrane partitions.

Original languageEnglish
Pages (from-to)9977-9984
Number of pages8
Issue number33
Publication statusPublished - 2020 Aug 25


Dive into the research topics of 'Internalization Mechanisms of Pyridinium Sulfobetaine Polymers Evaluated by Induced Protic Perturbations on Cell Surfaces'. Together they form a unique fingerprint.

Cite this