ABSTRACT
Endometriosis is a common gynaecological disease associated with pelvic pain and infertility. Current treatments include oral contraceptives combined with nonsteroidal anti-inflammatory drugs or surgery to remove lesions, all of which provide a temporary but not complete cure. Here we identify an endometriosis-targeting peptide that is internalized by cells, designated z13, using phage display. As most endometriosis occurs on organ surfaces facing the peritoneum, we subtracted a phage display library with female mouse peritoneum tissue and selected phage clones by binding to human endometrial epithelial cells. Proteomics analysis revealed the z13 receptor as the cyclic nucleotide-gated channel ß3, a sorting pathway protein. We then linked z13 with an apoptosis-inducing peptide and with an endosome-escaping peptide. When these peptides were co-administered into the peritoneum of baboons with endometriosis, cells in lesions selectively underwent apoptosis with no effect on neighbouring organs. Thus, this study presents a strategy that could be useful to treat peritoneal endometriosis in humans.
Subject(s)
Apoptosis/drug effects , Endometriosis/drug therapy , Molecular Targeted Therapy/methods , Peptides/pharmacology , Amino Acid Sequence , Animals , Cyclic Nucleotide-Gated Cation Channels/metabolism , DNA-Binding Proteins/metabolism , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Endometriosis/pathology , Endometrium/pathology , Epithelial Cells/metabolism , Female , Humans , Mice, Inbred C57BL , Molecular Sequence Data , Papio , Peptide Library , Peptides/metabolism , Peritoneal Diseases/drug therapy , Peritoneal Diseases/pathologyABSTRACT
Ten laboratory strains of oral microorganisms and 17 recent clinical isolates were examined for their ability to concentrate fluoride from a 1 ppm (0.05 mM NaF( fluoride solution. The laboratory strains concentrated the ion from two- to six-fold over the surrounding media. Clinical isolates of Actinomyces concentrated the ion to similar levels to the laboratory strains of this organism; however, clinical isolates of Streptococcus mutans and S. sanguis concentrated the fluoride significantly less than any of the laboratory strains examined.
