Biodegradable hypericin-containing nanoparticles for necrosis targeting and fluorescence imaging.

Necrosis targeting and imaging has significant implications for evaluating tumor growth, therapeutic response, and delivery of therapeutics to peri-necrotic 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 due to 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) (PEG-PCL) 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 post-injection, with near-complete clearance at 96 h post-injection. Hyp-NP was shown to be tightly localized within necrotic tumor zones. Histologic 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.