Exploiting cyanine dye J-aggregates/monomer equilibrium in hydrophobic protein pockets for efficient multi-step phototherapy: an innovative concept for smart nanotheranostics

PICCHIO, MATÍAS L.; BERGUEIRO, JULIAN; WEDEPOHL, STEFANIE; MINARI, ROQUE J.; ALVAREZ IGARZABAL, CECILIA I.; GUGLIOTTA, LUIS M.; CUGGINO, JULIO C.; CALDERÓN, MARCELO

Nanoscale

Royal Society of Chemistry

Año: 2021 vol. 13 p. 8909 - 8921

2040-3364

After several decades of development in the field of near-infrared (NIR) dyes for photothermal therapy(PTT), indocyanine green (ICG) still remains the only FDA-approved NIR contrast agent. However, uponNIR light irradiation ICG can react with molecular oxygen to form reactive oxygen species and degradethe ICG core, losing the convenient dye properties. In this work, we introduce a new approach forexpanding the application of ICG in nanotheranostics, which relies on the confinement of self-organizedJ-type aggregates in hydrophobic protein domains acting as monomer depots. Upon the fast photobleaching,while the dye is irradiated, this strategy permits the equilibrium-driven monomer replacementafter each irradiation cycle that radically increases the systems? effectivity and applicability. Gadoliniumdopedcasein micelles were designed to prove this novel concept at the same time as endowing thenanosystems with further magnetic resonance imaging (MRI) ability for dual-modal imaging-guided PTT.By teaching a new trick to a very old dog, the clinical prospect of ICG will undoubtedly be boosted layingthe foundation for novel therapeutics. It is anticipated that future research could be expanded to otherrelevant J-aggregates-forming cyanine dyes or nanocrystal formulations of poorly water-solublephotosensitizers.