Biodegradable Hypericin-Containing Nanoparticles for Necrosis Targeting and Fluorescence Imaging

Xiangjun Han, Olena Taratula, Oleh Taratula, Ke Xu, Anna St Lorenz, Abraham Moses, Younes Jahangiri, Guibo Yu, Khashayar Farsad

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Necrosis targeting and imaging has significant implications for evaluating tumor growth, therapeutic response, and delivery of therapeutics to perinecrotic tumor zones. Hypericin is a hydrophobic molecule with high necrosis affinity and fluorescence imaging properties. To date, the safe and effective delivery of hypericin to areas of necrosis in vivo remains a challenge because of its incompatible biophysical properties. To address this issue, we have developed a biodegradable nanoparticle (Hyp-NP) for delivery of hypericin to tumors for necrosis targeting and fluorescence imaging. The nanoparticle was developed using methoxy poly(ethylene glycol)-b-poly(ϵ-caprolactone) and hypericin by a modified solvent evaporation technique. The size of Hyp-NP was 19.0 ± 1.8 nm from cryo-TEM and 37.3 ± 0.7 nm from dynamic light-scattering analysis with a polydispersity index of 0.15 ± 0.01. The encapsulation efficiency of hypericin was 95.05% w/w by UV-vis absorption. After storage for 30 days, 91.4% hypericin was retained in Hyp-NP with nearly no change in hydrodynamic size, representing nanoparticle stability. In an ovarian cancer cell line, Hyp-NP demonstrated cellular internalization with intracellular cytoplasmic localization and preserved fluorescence and necrosis affinity. In a mouse subcutaneous tumor model, tumor accumulation was noted at 8 h postinjection, with near-complete clearance at 96 h postinjection. Hyp-NP was shown to be tightly localized within necrotic tumor zones. Histological analysis of harvested organs demonstrated no gross abnormalities, and in vitro, no hemolysis was observed. This proof-of-concept study demonstrates the potential clinical applications of Hyp-NP for necrosis targeting.

Original languageEnglish (US)
Pages (from-to)1538-1545
Number of pages8
JournalMolecular Pharmaceutics
Volume17
Issue number5
DOIs
StatePublished - May 4 2020

Keywords

  • Fluorescence
  • Hypericin
  • Necrosis
  • Tumor
  • nanoparticle

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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