Metal Chelation Modulates Phototherapeutic Properties of Mitoxantrone-loaded Porphyrin–Phospholipid Liposomes
Autor: | Dandan Luo, Sophie L. Wang, Kevin A. Carter, Jonathan F. Lovell, Shuai Shao, Jumin Geng |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Male
Porphyrins genetic structures Infrared Rays Phospholipid Pharmaceutical Science Mice Nude 02 engineering and technology 010402 general chemistry Photochemistry 01 natural sciences behavioral disciplines and activities Article chemistry.chemical_compound Mice Drug Discovery Tumor Cells Cultured Animals Humans Chelation Phospholipids chemistry.chemical_classification Reactive oxygen species Liposome Singlet Oxygen Singlet oxygen Lasers Free base Phototherapy 021001 nanoscience & nanotechnology Porphyrin Xenograft Model Antitumor Assays 0104 chemical sciences Pancreatic Neoplasms Zinc chemistry Liposomes Molecular Medicine Mitoxantrone 0210 nano-technology Phototoxicity Copper Nuclear chemistry |
Popis: | Liposomes incorporating porphyrin-phospholipid (PoP) can be formulated to release entrapped contents in response to near-infrared (NIR) laser irradiation. Here, we examine effects of chelating copper or zinc into the PoP. Cu(II) and Zn(II) PoP liposomes, containing 10 molar % HPPH-lipid, exhibited unique photophysical properties and released entrapped cargo in response to NIR light. Cu-PoP liposomes exhibited minimal fluorescence and reduced production of reactive oxygen species upon irradiation. Zn-PoP liposomes retained fluorescence and singlet oxygen generation properties; however, they rapidly self-bleached under laser irradiation. Compared to the free base form, both Cu- and Zn-PoP liposomes exhibited reduced phototoxicity in mice. When loaded with mitoxantrone and administered intravenously at 5 mg/kg to mice bearing human pancreatic cancer xenografts, synergistic effects between the drug and the light treatment (for this particular dose and formulation) were realized with metallo-PoP liposomes. The drug-light-interval affected chemophototherapy efficacy and safety. |
Databáze: | OpenAIRE |
Externí odkaz: |