Biodegradable Hypericin-Containing Nanoparticles for Necrosis Targeting and Fluorescence Imaging
| Autor: | Ke Xu, Anna St Lorenz, Oleh Taratula, Xiangjun Han, Younes Jahangiri, Guibo Yu, Abraham S. Moses, Khashayar Farsad, Olena Taratula |
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| Rok vydání: | 2020 |
| Předmět: |
Fluorescence-lifetime imaging microscopy
Necrosis media_common.quotation_subject Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine In vivo Cell Line Tumor Neoplasms Drug Discovery medicine Animals Humans Internalization Perylene media_common Anthracenes Chemistry Optical Imaging 021001 nanoscience & nanotechnology medicine.disease In vitro Hemolysis Hypericin Biophysics Molecular Medicine Nanoparticles Female medicine.symptom 0210 nano-technology Intracellular |
| Zdroj: | Mol Pharm |
| ISSN: | 1543-8392 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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