Dextran-Benzoporphyrin Derivative (BPD) Coated Superparamagnetic Iron Oxide Nanoparticle (SPION) Micelles for T2-Weighted Magnetic Resonance Imaging and Photodynamic Therapy

Bioconjug Chem. 2019 Nov 20;30(11):2974-2981. doi: 10.1021/acs.bioconjchem.9b00676. Epub 2019 Nov 8.

Abstract

Photodynamic therapy (PDT) has attracted extensive attention in recent years as a noninvasive and locally targeted cancer treatment approach. Nanoparticles have been used to improve the solubility and pharmacokinetics of the photosensitizers required for PDT; however, nanoparticles also suffer from many shortcomings including uncontrolled drug release and low tumor accumulation. Herein, we describe a novel biodegradable nanoplatform for the delivery of the clinically used PDT photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) to tumors. Specifically, the hydrophobic photosensitizer BPD was covalently conjugated to the amine groups of a dextran-b-oligo (amidoamine) (dOA) dendron copolymer, forming amphiphilic dextran-BPD conjugates that can self-assemble into nanometer-sized micelles in water. To impart additional imaging capabilities to these micelles, superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated within the hydrophobic core to serve as a magnetic resonance imaging (MRI) contrast agent. The use of a photosensitizer as a hydrophobic building block enabled facile and reproducible synthesis and high drug loading capacity (∼30%, w/w). Furthermore, covalent conjugation of BPD to dextran prevents the premature release of drug during systemic circulation. In vivo studies show that the intravenous administration of dextran-BPD coated SPION nanoparticles results in significant MR contrast enhancement within tumors 24 h postinjection and PDT led to a significant reduction in the tumor growth rate.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Contrast Media / metabolism
  • Dextrans / chemistry*
  • Drug Liberation
  • Female
  • Ferric Compounds / chemistry
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Magnetite Nanoparticles / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Micelles
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Polymers / chemistry
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Contrast Media
  • Dextrans
  • Ferric Compounds
  • Magnetite Nanoparticles
  • Micelles
  • Photosensitizing Agents
  • Polymers
  • Porphyrins
  • benzoporphyrin D
  • ferric oxide