TY - JOUR
T1 - Control of Mitochondrial Localization Using Thermoresponsive Sulfobetaine Polymer
AU - Morimoto, Nobuyuki
AU - Oishi, Yoshifumi
AU - Yamamoto, Masaya
N1 - Funding Information:
The authors thank Prof. Hitoshi Takamura (Tohoku University) for his kind help about DLS measurements. N.M. acknowledges financial support from Grant‐in‐Aid for Scientific Research (B) (JP17H02096) from the Japan Society for the Promotion of Science (JSPS). Y.M. acknowledges financial support from Support Program for Interdisciplinary Research from Frontier Research Institute for Interdisciplinary Sciences (FRIS), Tohoku University.
Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2020/12
Y1 - 2020/12
N2 - Fast intracellular migration and controlled localization of molecules represent significant challenges for future applications of drug discovery and related fields. In this study, thermoresponsive sulfobetaine polymers with pyridinium cations are evaluated as biocompatible and mitochondria-localizing agents. Among the polymers, poly(3-(4-(2-methacrylamido)ethyl pyridinio-1-yl)propane-1-sulfonate), P(E-PySMAAm)14k (Mn = 14 000 g mol−1) exhibit thermoresponsiveness with an upper critical solution temperature like behavior in cell culture medium containing serum with minimal cytotoxicity. Upon the addition of P(E-PySMAAm)14k to HeLa cells at temperatures above the clearing point at 37 °C, effective localization is observed in mitochondria. However, increased intensity but nonspecific localization is observed below the clearing point at 4 °C. Doxorubicin is conjugated to the P(E-PySMAAm) and achieves effective mitochondrial delivery while maintaining drug efficacy. Such sulfobetaine polymers represent promising tools for intracellular delivery of molecules.
AB - Fast intracellular migration and controlled localization of molecules represent significant challenges for future applications of drug discovery and related fields. In this study, thermoresponsive sulfobetaine polymers with pyridinium cations are evaluated as biocompatible and mitochondria-localizing agents. Among the polymers, poly(3-(4-(2-methacrylamido)ethyl pyridinio-1-yl)propane-1-sulfonate), P(E-PySMAAm)14k (Mn = 14 000 g mol−1) exhibit thermoresponsiveness with an upper critical solution temperature like behavior in cell culture medium containing serum with minimal cytotoxicity. Upon the addition of P(E-PySMAAm)14k to HeLa cells at temperatures above the clearing point at 37 °C, effective localization is observed in mitochondria. However, increased intensity but nonspecific localization is observed below the clearing point at 4 °C. Doxorubicin is conjugated to the P(E-PySMAAm) and achieves effective mitochondrial delivery while maintaining drug efficacy. Such sulfobetaine polymers represent promising tools for intracellular delivery of molecules.
KW - drug delivery
KW - mitochondrial localization
KW - sulfobetaine polymer
KW - thermoresponsiveness
KW - upper critical solution temperature
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U2 - 10.1002/mabi.202000205
DO - 10.1002/mabi.202000205
M3 - Article
C2 - 32924287
AN - SCOPUS:85090950032
SN - 1616-5187
VL - 20
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 12
M1 - 2000205
ER -