Near-infrared activatable phthalocyanine-poly-L-glutamic acid conjugate: increased cellular uptake and light-dark toxicity ratio toward an effective photodynamic cancer therapy

Nanomedicine. 2017 May;13(4):1447-1458. doi: 10.1016/j.nano.2017.02.002. Epub 2017 Feb 16.

Abstract

In photodynamic therapy (PDT), the low absorptivity of photosensitizers in an aqueous environment reduces singlet oxygen generation efficiency and thereby decreases photosensitizing efficacy in biological conditions. To circumvent this problem, we designed a phthalocyanine-poly-L-glutamic acid conjugate (1-PG) made from a new phthalocyanine (Pc 1) monofunctionalized to allow adequate conjugation to PGA. The resulting 1-PG conjugate retained high absorptivity in the near-infrared (NIR) region at its λmax 675nm in an aqueous environment. The 1-PG conjugate demonstrated good singlet oxygen generation efficiency, increased uptake by 4 T1 breast cancer cells via clathrin-mediated endocytosis, and enhanced photocytotoxic efficacy. The conjugate also displayed a high light-dark toxicity ratio, approximately 1.5-fold greater than zinc phthalocyanine at higher concentration (10 μM), an important feature for the reduction of dark toxicity and unwanted side effects. These results suggest that the 1-PG conjugate could be a useful alternative for deep tissue treatment with enhanced anti-cancer (PDT) efficacy.

Keywords: Nano-structure; Near-infrared; Photodynamic therapy; Photosensitizer; Phthalocyanine; Poly-L-glutamic acid.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Endocytosis
  • Glutamic Acid / chemistry*
  • Indoles / chemistry*
  • Light
  • Mice
  • Molecular Structure
  • Nanoconjugates / chemistry*
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry*
  • Singlet Oxygen / chemistry

Substances

  • Indoles
  • Nanoconjugates
  • Photosensitizing Agents
  • Singlet Oxygen
  • Glutamic Acid
  • phthalocyanine