LyP-1-conjugated nanoparticles for targeting drug delivery to lymphatic metastatic tumors.

Abstract

Active tumor targeting by biodegradable nanoparticles has been widely studied for cancer diagnosis and therapy. However, target-specific nanoparticles for drug delivery to lymphatic metastases have not been reported yet due to the lack of specific markers in the tumor lymphatics. Recently, peptide LyP-1 has been recognized for its specific home to tumors and their lymphatics. In this study, we tested the possibility of LyP-1 serving as a target-specific peptide of PEG-PLGA nanoparticles to tumor lymph metastases. LyP-1 was synthesized by using Boc-protected amino acids. The copolymers of maleimide-PEG-PLGA were formed by the conjugation of maleimide-PEG-NH(2) to PLGA-COOH, which were applied to prepare pegylated nanoparticles with mPEG-PLGA by means of double emulsion/solvent evaporation technique. LyP-1 with sulfhydryl group was conjugated to the maleimide function located at the distal end of PEG surrounding the nanoparticle surface. LyP-1-conjugated PEG-PLGA nanoparticle (LyP-1-NPs) had a round and regular shape with a diameter around 90 nm. In vitro, cellular uptake of LyP-1-NPs was about four times of that of PEG-PLGA nanoparticles without LyP-1 (NPs). In vivo, the uptake of LyP-1-NPs in metastasis lymph nodes was about eight times of that of NPs. This study indicates that LyP-1-NP is a promising carrier for target-specific drug delivery to lymphatic metastatic tumors.

• Authors: Guopei Luo, Xianjun Yu, Chen Jin, Feng Yang, Deliang Fu, Jiang Long, Jin Xu, Changyou Zhan, Weiyue Lu
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 385 Issue 1-2 Pg. 150-6 (Jan 29 2010) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 19825404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2009 Elsevier B.V. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• LyP-1 peptide
• Maleimides
• Peptides, Cyclic
• poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer
• Polyglactin 910
• Polyethylene Glycols

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, metabolism)
• Biological Transport
• Cell Line, Tumor
• Chemistry, Pharmaceutical
• Drug Carriers
• Humans
• Lymph Nodes (drug effects, metabolism, pathology)
• Lymphatic Metastasis
• Maleimides (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles
• Pancreatic Neoplasms (drug therapy, metabolism, secondary)
• Particle Size
• Peptides, Cyclic (chemistry, metabolism)
• Polyethylene Glycols (chemistry)
• Polyglactin 910 (chemistry)
• Protein Binding
• Surface Properties
• Technology, Pharmaceutical (methods)