Different effects of the immunomodulatory drug GMDP immobilized onto aminopropyl modified and unmodified mesoporous silica nanoparticles upon peritoneal macrophages of women with endometriosis.
The aim of the present work was to compare in vitro the possibility of application of unmodified silica nanoparticles (UMNPs) and modified by aminopropyl groups silica nanoparticles (AMNPs) for topical delivery of immunomodulatory drug GMDP to the peritoneal macrophages of women with endometriosis. The absence of cytotoxic effect and high cellular uptake was demonstrated for both types of silica nanoparticles. The immobilization of GMDP on the UMNPs led to the suppression of the stimulatory effect of GMDP on the membrane expression of scavenger receptors SR-AI and SR-B, mRNAs expression of NOD2 and RAGE, and synthesis of proteolytic enzyme MMP-9 and its inhibitor TIMP-1. GMDP, immobilized onto AMNPs, enhanced the initially reduced membrane expression of SRs and increased NOD2, RAGE, and MMP-9 mRNAs expression by macrophages. Simultaneously high level of mRNAs expression of factors, preventing undesirable hyperactivation of peritoneal macrophages (SOCS1 and TIMP-1), was observed in macrophages incubated in the presence of GMDP, immobilized onto AMNPs. The effect of AMNPs immobilized GMDP in some cases exceeded the effect of free GMDP. Thus, among the studied types of silica nanoparticles, AMNPs are the most suitable nanoparticles for topical delivery of GMDP to the peritoneal macrophages.
Federal State Institution "Ivanovo Research Institute of Maternity and Childhood named V.N.Gorodkov" of Healthy Ministry of Russian Federation, Pobedy Street 20, Ivanovo 153045, Russia.
Yuliya
Y
Antsiferova
Federal State Institution "Ivanovo Research Institute of Maternity and Childhood named V.N.Gorodkov" of Healthy Ministry of Russian Federation, Pobedy Street 20, Ivanovo 153045, Russia.
Nataliya
N
Sotnikova
G.A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, Akademicheskaya 1, Ivanovo 153045, Russia.
Elena
E
Parfenyuk
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D000276:Adjuvants, Immunologic; D004715:Endometriosis / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000737:chemistry; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D007155:Immunologic Factors; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C021611:aminopropyl silica gel; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine; D012822:Silicon Dioxide