RRC ID 67714
Author Kudo S, Nagasaki Y.
Title A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(l-arginine)-based nanoparticles.
Journal J Control Release
Abstract In the immune system, macrophages in tumor tissue generate nitric oxide (NO), producing versatile effects including apoptosis of tumor cells, because inducible NO synthase (iNOS) in the cytoplasm of a macrophage produces NO using l-arginine as a substrate. Here, we propose novel NO-triggered immune therapeutics based on our newly designed nanoparticle system. We designed a poly(ethylene glycol)-block-poly(l-arginine) (i.e., PEG-b-P(l-Arg)) block copolymer and prepared polyion complex micelles (PEG-b-P(l-Arg)/m) composed of PEG-b-P(l-Arg) and chondroitin sulfate for systemic anticancer immunotherapy. iNOS treatment of PEG-b-P(l-Arg) did not generate NO, but NO molecules were detected after trypsin pretreatment, indicating that hydrolysis of P(l-Arg) to monomeric arginine was taking place in vitro. RAW264.7 macrophages abundantly generated NO from the PEG-b-P(l-Arg)/m in comparison with control micelles; this finding is indicative of robustness of the proposed method. It is interesting to note that systemic administration of PEG-b-P(l-Arg)/m had no noticeable adverse effects and suppressed the tumor growth rate in C26 tumor-bearing mice in a dose-dependent manner. Our newly designed nanoparticle-assisted arginine delivery system seems to hold promise as an NO-mediated anticancer immunotherapy.
Volume 217
Pages 256-62
Published 2015-11-10
DOI 10.1016/j.jconrel.2015.09.019
PII S0168-3659(15)30121-8
PMID 26386436
MeSH Animals Antineoplastic Agents / administration & dosage* Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacokinetics Cell Line, Tumor Macrophages / drug effects* Macrophages / metabolism Male Mice, Inbred BALB C Nanoparticles / administration & dosage* Nanoparticles / chemistry Neoplasms / drug therapy Neoplasms / metabolism Neoplasms / pathology Nitric Oxide / metabolism* Nitric Oxide Synthase Type II / metabolism Peptides / administration & dosage* Peptides / chemistry Peptides / pharmacokinetics Polyethylene Glycols / administration & dosage* Polyethylene Glycols / chemistry Polyethylene Glycols / pharmacokinetics Tumor Burden / drug effects
IF 7.727
Human and Animal Cells Colon-26(RCB2657)