Imaging-Guided Delivery of a Hydrophilic Drug to Eukaryotic Cells Based on Its Hydrophobic Ion Pairing with Poly(hexamethylene guanidine) in a Maleated Chitosan Carrier
Sofia A. Zakharenkova,
Marina I. Lebedeva,
Alexandra N. Lebedeva,
Irina A. Doroshenko,
Ksenya Yu Vlasova,
Anastasiya A. Bartoshevich,
Vladimir M. Senyavin,
Sergey S. Abramchuk,
George G. Krivtsov,
Alexander A. Ezhov,
Tatyana A. Podrugina,
Natalia L. Klyachko,
Mikhail K. Beklemishev
Affiliations
Sofia A. Zakharenkova
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Marina I. Lebedeva
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Alexandra N. Lebedeva
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Irina A. Doroshenko
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Ksenya Yu Vlasova
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Anastasiya A. Bartoshevich
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Vladimir M. Senyavin
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Sergey S. Abramchuk
Laboratory of Physical Chemistry of Polymers, Nesmeyanov Institute of Organoelement Compounds (INEOS RAS), 119991 Moscow, Russia
George G. Krivtsov
Mechnikov Research Institute for Vaccines and Sera, 105064 Moscow, Russia
Alexander A. Ezhov
Faculty of Physics, Lomonosov Moscow State University, 119991 Moscow, Russia
Tatyana A. Podrugina
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Natalia L. Klyachko
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Mikhail K. Beklemishev
Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia
Imaging-guided delivery is developed for hydrophobic drugs, and to a much lesser extent, hydrophilic ones. In this work we have designed a novel strategy for real-time monitoring of hydrophilic drug delivery. Traditionally, the drug and the dye are covalently attached to a nanocarrier or are electrostatically adsorbed. Recently, we found an efficient way to bind the drug by ion-paring with an appropriate counter-ion to form the aggregate that embeds a hydrophobic dye with a considerable fluorescence enhancement. We synthesized a series of carbocyanine dyes of hydrophobicity sufficient for solubilization in hydrophobic ion pairs, which restores their emission in the near-infrared (NIR) region upon the formation of the ternary aggregates. To avoid using toxic surfactants, we applied an amphiphilic polymer-oligomer poly(hexamethylene guanidine) (PHMG) as a counter-ion. Сeftriaxone was used as a model hydrophilic drug ensuring the highest fluorescent signal. The so-formed drug–counter-ion–dye aggregates were encapsulated into a cross-linked maleated chitosan carrier. Confocal laser scanning microscopy (CLSM) studies have demonstrated internalization of the encapsulated model drug by breast adenocarcinoma cells at 40 min after treatment. These results suggest the potential application of hydrophobic ion pairs containing an NIR dye in imaging-guided delivery of hydrophilic compounds.
