Rational design of dendritic thermo-responsive nanogels that undergo phase transition on endolysosomal conditions

GUIDO NOE RIMONDINO; H WEDEPOHL; MIRIAM C. STRUMIA; GUIDO NOE RIMONDINO; H WEDEPOHL; MIRIAM C. STRUMIA; ENRICO MICELLI; S. THIERBACH; MARISA MARTINELLI; MARIA MOLINA; ENRICO MICELLI; E. RÜHL; S. THIERBACH; M. CALDERON; MARISA MARTINELLI; MARIA MOLINA; E. RÜHL; M. CALDERON

Journal Material Chemistry B

ROYAL SOC CHEMISTRY

Año: 2017 vol. 5 p. 866 - 874

2050-750X

In the last few decades, the synthesis of nanodevices has become a very active research field with manyapplications in biochemistry, biotechnology, and biomedicine. However, there is still a great need for smartnanomaterials that can sense and respond to environmental changes. Temperature- and pH-responsivenanogels (NGs), which are prepared in a one-pot synthesis from N-isopropylacrylamide (NiPAm) and aNewkome-type dendron (ABC) bearing carboxylic acid groups, are being investigated as multi-responsivedrug carriers. As a result, NGs have been developed that are able to undergo a reversible volume phasetransition triggered by acidic conditions, like the ones found in endolysosomal compartments of cancercells. The NGs have been thoroughly characterized using dynamic light scattering and spectroscopies, suchas infrared, nuclear magnetic resonance, UV-visible, and stimulated Raman. Strong hydrogen bonds havebeen detected when the ABC moieties are deprotonated, which has led to changes in the transitiontemperatures of the NGs and a reversible, pH-dependent aggregation. This pH-dependent phase changewas exploited for the effective encapsulation and sustained release of the anticancer drug cisplatin andresulted in a faster release of the drug at endolysosomal pH values. The cisplatin-loaded NGs have exhibitedhigh toxicities against A549 cells in vitro, while the unloaded NGs have been found to be not cytotoxic andhemocompatible.