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Folate-modified PLGA nanoparticles for tumor-targeted delivery of pheophorbide a in vivo.

Abstract
Targeted drug delivery has been an important issue for tumor therapy including photodynamic therapy (PDT). The purpose of our study is to increase the targeting efficiency of photosensitizer (PS) using folate-modified nanoparticles (NPs) to tumor site in vivo. Folate receptor is over-expressed on the surface of many human cancer cells. We prepared poly (lactic-co-glycolic acid) (PLGA) NPs containing pheophorbide a (Pba), a PS that is used in PDT and generates free radical for killing cancer cells. The surface of NPs was composed of phospholipids modified with polyethylene glycol (PEG) and folate (FA). The size of the resulting FA-PLGA-Pba NPs was about 200 nm in PBS at pH 7.4 and they were stable for long time. They showed faster cellular uptake to MKN28 human gastric cancer cell line than control PLGA-Pba NPs by high-affinity binding with folate receptors on cell surface. In MTT assay, FA-PLGA-Pba NPs also showed enhanced tumor cell killing compared to control PLGA-Pba NPs. In vivo and ex vivo imaging showed high accumulation of FA-PLGA-Pba NPs in tumor site during 24 h after intravenous injection to MKN28 tumor-bearing mice model. These results demonstrate that our FA-PLGA-Pba NPs are useful for tumor-targeted delivery of PS for cancer treatment by PDT.
AuthorsJihwan Son, Seung Mok Yang, Gawon Yi, Yoon Jin Roh, Hyeji Park, Jae Myung Park, Myung-Gyu Choi, Heebeom Koo
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 498 Issue 3 Pg. 523-528 (04 06 2018) ISSN: 1090-2104 [Electronic] United States
PMID29518390 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Inc. All rights reserved.
Chemical References
  • Drug Carriers
  • Photosensitizing Agents
  • Chlorophyll
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Folic Acid
  • pheophorbide a
Topics
  • Animals
  • Cell Line, Tumor
  • Chlorophyll (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
  • Drug Carriers (chemistry)
  • Drug Delivery Systems
  • Folic Acid (chemistry)
  • Humans
  • Lactic Acid (chemistry)
  • Mice, Nude
  • Nanoparticles (chemistry)
  • Photochemotherapy
  • Photosensitizing Agents (administration & dosage, pharmacokinetics, therapeutic use)
  • Polyglycolic Acid (chemistry)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Stomach Neoplasms (drug therapy, pathology)

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