Dendron-Functionalized Polyglutamate-Pyropheophorbide-a Conjugates as Nanomedicines for Breast Cancer Photodynamic Therapy

Macromol Rapid Commun. 2021 May;42(9):e2100013. doi: 10.1002/marc.202100013. Epub 2021 Mar 24.

Abstract

Photodynamic therapy (PDT) has shown its promise in the treatment of cancer. Herein, a dendron-functionalized polyglutamic acid (PGA) polymer (PG-L8G-Ppa-Dendron, PGPD) is synthesized and it is conjugated with pyropheophorbide-a (Ppa) for the first time to treat triple negative breast cancer (TNBC), whereas a linear polyglutamate-Ppa conjugate (PGP) is synthesized as a control. Compared to the linear counterpart, the glycosylated polymer-based PGPD with a dendritic structure has excellent solubility and it self-assembles to form uniform-sized nanoparticles. PGPD displays a highly effective PDT effect in the animal model, evidenced with effective induction of reactive oxygen species (ROS) production and cell apoptosis. This may be due to an enhanced efficiency in delivery and accumulation of Ppa by this glycosylated dendritic polymer at tumor sites. Therefore, PGPD can be a highly effective and biosafe nanoagent for PDT of TNBC.

Keywords: cancer therapies; dendrimers; nanomedicines; photodynamic therapies; polyglutamic acids.

MeSH terms

  • Animals
  • Breast Neoplasms* / drug therapy
  • Cell Line, Tumor
  • Dendrimers*
  • Female
  • Humans
  • Nanomedicine
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use
  • Polyglutamic Acid

Substances

  • Dendrimers
  • Photosensitizing Agents
  • Polyglutamic Acid