Axial PEGylation of Tin Octabutoxy Naphthalocyanine Extends Blood Circulation for Photoacoustic Vascular Imaging

Bioconjug Chem. 2016 Jul 20;27(7):1574-8. doi: 10.1021/acs.bioconjchem.6b00280. Epub 2016 Jun 15.

Abstract

Attachment of polyethylene glycol (PEG) can prolong blood circulation of biological molecules, a useful trait for a vascular imaging agent. Here, we present a route for modifying octabutoxy naphthalocyanine (ONc) with PEG, via axial conjugation following ONc chelation with Sn(IV) chloride (Sn-ONc). Tin chelation caused ONc absorbance to shift from 860 to 930 nm. Hydroxy terminated PEG was treated with sodium and then was axially attached to the tin, generating PEG-Sn-ONc. Unlike ONc or Sn-ONc, PEG-Sn-ONc was soluble in methanol. ONc and PEG-Sn-ONc were dissolved in polysorbate solutions and administered to mice intravenously. PEG-Sn-ONc demonstrated substantially longer blood circulation time than ONc, with a 4 times longer half-life and a nearly 10 times greater area under the curve. PEG-Sn-ONc gave rise to photoacoustic contrast and could be used for noninvasive brain vessel imaging even 24 h following injection. This work demonstrates that nonmetallic naphthalocyanines can be chelated with tin, and be axially modified with PEG for enhanced circulation times for long-term vascular imaging with photoacoustic tomography.

MeSH terms

  • Animals
  • Brain / blood supply
  • Cerebrovascular Circulation*
  • Mice
  • Naphthalenes / chemistry
  • Organometallic Compounds / chemistry*
  • Photoacoustic Techniques / methods*
  • Polyethylene Glycols / chemistry*
  • Tin / chemistry*
  • Tomography / methods*

Substances

  • Naphthalenes
  • Organometallic Compounds
  • naphthalene
  • Polyethylene Glycols
  • Tin