A Porphyrin Dimer-GdDOTA Conjugate as a Theranostic Agent for One- and Two-Photon Photodynamic Therapy and MRI

Bioconjug Chem. 2018 Nov 21;29(11):3726-3738. doi: 10.1021/acs.bioconjchem.8b00634. Epub 2018 Oct 10.

Abstract

A molecular theranostic agent designed for photodynamic therapy (PDT) treatment in the near-infrared and for imaging tissue tumors with magnetic resonance imaging (MRI) is reported. It consists of a linear π-conjugated Zn(II) porphyrin dimer linked at each extremity to a GdDOTA-type complex. This agent has shown very promising potential for PDT applications with good singlet oxygen generation in DMSO and high linear absorption in the near-infrared (λmax = 746 nm, ε ≈ 105 M-1 cm-1). Moreover, this molecule has a propensity for two-photon excited PDT with high two-photon cross sections (∼8000 GM in 880-930 nm range), which should allow for deeper tumor treatments and higher spatial precision as compared to conventional one-photon PDT. Regarding the MRI contrast agent properties, the molecule has shown superior relaxivity (14.4 mM-1 s-1 at 40 MHz, 298 K) in comparison to clinical contrast agents and the ability to be internalized in cells, thanks to its amphiphilic character. Irradiation of HeLa cells using either one-photon (740 nm) or two-photon excitation (910 nm) has led in both cases to important cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dimerization
  • HeLa Cells
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / therapeutic use*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Neoplasms / diagnostic imaging*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / therapeutic use*
  • Photochemotherapy / methods
  • Photons
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / chemistry
  • Porphyrins / therapeutic use*
  • Singlet Oxygen / metabolism
  • Theranostic Nanomedicine / methods

Substances

  • Heterocyclic Compounds
  • Organometallic Compounds
  • Photosensitizing Agents
  • Porphyrins
  • Singlet Oxygen
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate