In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics

J Mater Chem B. 2022 Jul 13;10(27):5279-5290. doi: 10.1039/d2tb00705c.

Abstract

Through the activation of packing arrangements of dyes to modulate their photophysical and/or photochemical properties, not only new NIR-II dyes but tumor-specific NIR-II imaging and therapy can also be achieved. Herein, we designed an acid-responsive polypeptide nanoparticle (P-ipr@Gal) encapsulated with a pH-sensitive amphiphilic polypeptide (P-ipr) as a carrier for the galactose-conjugated BODIPY (Gal-BDP) dye. When P-ipr@Gal NPs are enriched in tumor regions by the EPR effect, the acidic microenvironment (pH 6.4-6.8) promotes the disintegration of P-ipr@Gal nanomicelles and the release of sufficient Gal-BDP. The protonation of the julolidine nitrogen of the Gal-BDP dye switched on the molecular stacking transformation from the H-aggregate to J-aggregate. The J-aggregate significantly enhanced the redshift absorption and emission intensity, which enhanced the fluorescence brightness and photothermal therapeutic effect in the tumor region. We also prepared J-aggregates PAsp@Gal with non-acidic responsive polyaspartic acid benzyl esters (PAsp) encapsulated Gal-BDP, which remained "always-on" with J-aggregate characteristics. The P-ipr@Gal (or PAsp@Gal) J-aggregate has a maximum emission peak redshifted to nearly 1064 nm, with a 3.5-fold increase in the emission intensity compared to the H-aggregate at pH 7.4. Based on the effective accumulation of tumor sites and considerable PCE (>40%), P-ipr@Gal nanoparticles have a lower background and higher tumor background ratio, which makes them a potential NIR-II imaging-guided photothermal therapy agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds
  • Coloring Agents
  • Galactose
  • Humans
  • Nanoparticles* / chemistry
  • Neoplasms*
  • Peptides
  • Tumor Microenvironment

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Coloring Agents
  • Peptides
  • Galactose