In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages.

Abstract

Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases.

• Authors: Bong Gu Yi, Ok Kyu Park, Myeong Seon Jeong, Seung Hae Kwon, Jae In Jung, Seongsoo Lee, Sungwoo Ryoo, Sung Eun Kim, Jin Won Kim, Won-Jin Moon, Kyeongsoon Park
• Journal: International journal of biological macromolecules (Int J Biol Macromol) Vol. 97 Pg. 181-189 (Apr 2017) ISSN: 1879-0003 [Electronic] Netherlands
• PMID: 28082222 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Chlorophyllides
• Drug Carriers
• Lipopolysaccharides
• Porphyrins
• RNA, Messenger
• Scavenger Receptors, Class A
• Deoxycholic Acid
• phytochlorin
• Dextran Sulfate

Topics

• Animals
• Biological Transport
• Chlorophyllides
• Deoxycholic Acid (chemistry)
• Dextran Sulfate (chemistry)
• Drug Carriers (chemistry)
• Gene Expression Regulation (drug effects, radiation effects)
• Hydrophobic and Hydrophilic Interactions
• Intracellular Space (metabolism)
• Lipopolysaccharides (pharmacology)
• Macrophage Activation (drug effects, radiation effects)
• Macrophages (drug effects, immunology, radiation effects)
• Mice
• Molecular Targeted Therapy
• Nanoparticles (chemistry)
• Photochemotherapy
• Porphyrins (chemistry, metabolism, pharmacology)
• RAW 264.7 Cells
• RNA, Messenger (genetics, metabolism)
• Scavenger Receptors, Class A (genetics, metabolism)
• Solubility