Control of Mitochondrial Localization Using Thermoresponsive Sulfobetaine Polymer

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 (M_n  = 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.