Tumor-Specific Formation of Enzyme-Instructed Supramolecular Self-Assemblies as Cancer Theranostics

ACS Nano. 2015 Oct 27;9(10):9517-27. doi: 10.1021/acsnano.5b03874. Epub 2015 Aug 27.

Abstract

Despite the effort of developing various nanodelivery systems, most of them suffer from undesired high uptakes by the reticuloendothelial system, such as liver and spleen. Herein we develop an endogenous phosphatase-triggered coassembly strategy to form tumor-specific indocyanine green (ICG)-doped nanofibers (5) for cancer theranostics. Based on coordinated intermolecular interactions, 5 significantly altered near-infrared absorbance of ICG, which improves the critical photoacoustic and photothermal properties. The phosphatase-instructed coassembly process, as well as its theranostic capability, was successfully conducted at different levels ranging from in vitro, living cell, tissue mimic, to in vivo. Specifically, the tumor uptake of ICG was markedly increased to 15.05 ± 3.78%ID/g, which was 25-fold higher than that of free ICG (0.59 ± 0.24%ID/g) at 4 h after intravenous injection. The resulting ultrahigh T/N ratios (>15) clearly differentiated tumors from the surrounding normal tissue. Complete tumor elimination with high therapeutic accuracy has been successfully achieved upon laser irradiation (0.8 W/cm(2), 5 min) within 24-48 h postinjection. As the first example, in vivo formation of tumor-specific ICG-doped nanofiber for PTT theranostics owns the immense potential for clinical translation of personalized nanomedicine with targeted drug delivery as well as for cancer theranostics.

Keywords: fluorescence imaging; indocyanine green; nanofibers; photoacoustic imaging; photothermal therapy; self-assembly; theranostics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Coloring Agents / chemistry
  • Coloring Agents / metabolism
  • Coloring Agents / pharmacokinetics
  • Coloring Agents / therapeutic use*
  • Drug Delivery Systems
  • HeLa Cells
  • Humans
  • Hypothermia, Induced / methods
  • Indocyanine Green / chemistry
  • Indocyanine Green / metabolism
  • Indocyanine Green / pharmacokinetics
  • Indocyanine Green / therapeutic use*
  • Mice
  • Models, Molecular
  • Nanofibers / chemistry
  • Nanofibers / therapeutic use*
  • Neoplasms / diagnosis*
  • Neoplasms / therapy*
  • Optical Imaging / methods
  • Phosphoric Monoester Hydrolases / metabolism
  • Photoacoustic Techniques / methods
  • Phototherapy / methods
  • Theranostic Nanomedicine / methods*

Substances

  • Coloring Agents
  • Phosphoric Monoester Hydrolases
  • Indocyanine Green