Facile Supramolecular Approach to Nucleic-Acid-Driven Activatable Nanotheranostics That Overcome Drawbacks of Photodynamic Therapy

ACS Nano. 2018 Jan 23;12(1):681-688. doi: 10.1021/acsnano.7b07809. Epub 2017 Dec 22.

Abstract

Supramolecular chemistry provides a "bottom-up" method to fabricate nanostructures for biomedical applications. Herein, we report a facile strategy to directly assemble a phthalocyanine photosensitizer (PcS) with an anticancer drug mitoxantrone (MA) to form uniform nanostructures (PcS-MA), which not only display nanoscale optical properties but also have the capability of undergoing nucleic-acid-responsive disassembly. These supramolecular assemblies possess activatable fluorescence emission and singlet oxygen generation associated with the formation of free PcS, mild photothermal heating, and a concomitant chemotherapeutic effect associated with the formation of free MA. In vivo evaluations indicate that PcS-MA nanostructures have a high level of accumulation in tumor tissues, are capable of being used for cancer imaging, and have significantly improved anticancer effect compared to that of PcS. This study demonstrates an attractive strategy for overcoming the limitations of photodynamic cancer therapy.

Keywords: activatable; nanotheranostics; nucleic-acid-responsive disassembly; photodynamic therapy; supramolecular assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacokinetics
  • Delayed-Action Preparations / therapeutic use
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacokinetics
  • Indoles / therapeutic use*
  • Isoindoles
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitoxantrone / chemistry
  • Mitoxantrone / pharmacokinetics
  • Mitoxantrone / therapeutic use*
  • Models, Molecular
  • Nanostructures / chemistry
  • Nanostructures / therapeutic use*
  • Nanostructures / ultrastructure
  • Neoplasms / diagnostic imaging*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Nucleic Acids / metabolism
  • Optical Imaging / methods
  • Photochemotherapy / methods
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacokinetics
  • Photosensitizing Agents / therapeutic use*
  • Theranostic Nanomedicine / methods*

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Indoles
  • Isoindoles
  • Nucleic Acids
  • Photosensitizing Agents
  • Mitoxantrone
  • phthalocyanine