pH-responsive dendritic core-multishell nanocarriers.
In this paper we describe novel pH-responsive core-multishell (CMS) nanocarrier (pH-CMS), obtained by introducing an aromatic imine linker between the shell and the core. At a pH of 5 and lower the used imine linker was rapidly cleaved as demonstrated by NMR studies. The CMS nanocarriers were loaded with the dye Nile red (NR) and the anticancer drug doxorubicin (DOX), respectively. The transport capacities were determined using UV/Vis spectroscopy, and the sizes of the loaded and unloaded CMS nanocarriers were investigated using dynamic light scattering (DLS). We could show that CMS nanocarriers efficiently transported NR in supramolecular aggregates, while DOX was transported in a unimolecular fashion. After cellular uptake the DOX-loaded pH-responsive nanocarriers showed higher toxicities than the stable CMS nanocarriers. This is due to a more efficient DOX release caused by the cleavage of the pH-labile imine bond at lower pH within the intracellular compartments.
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, 14195 Berlin, Germany.
Emanuel
E
Fleige
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, 14195 Berlin, Germany.
Katharina
K
Achazi
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, 14195 Berlin, Germany.
Karolina
K
Schaletzki
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, 14195 Berlin, Germany.
Therese
T
Triemer
Freie Universität Berlin, Institut für Chemie und Biochemie, Takustraße 3, 14195 Berlin, Germany. Electronic address: haag@chemie.fu-berlin.de.
Rainer
R
Haag
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000008:administration & dosage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007097:Imines / Q000737:chemistry; D008027:Light; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D010078:Oxazines / Q000008:administration & dosage; D012542:Scattering, Radiation
D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005456:Fluorescent Dyes; D007097:Imines; D010078:Oxazines; D004317:Doxorubicin; C044808:nile red
Doxorubicin; Drug delivery; Dynamic light scattering; Nile red; Real time cell analysis; Transport capacity