CD177-mediated nanoparticle targeting of human and mouse neutrophils.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Isoantigens/*metabolism ; Nanoparticles/*administration & dosage ; Neutrophils/*metabolism ; Receptors, Cell Surface/*metabolism; Animals ; CHO Cells ; Cricetulus ; GPI-Linked Proteins/metabolism ; Gene Knockdown Techniques ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Humans ; Mice ; Neutrophils/cytology ; Oligonucleotides, Antisense/administration & dosage ; Protein Binding ; RNA, Small Interfering ; Receptor, Anaphylatoxin C5a/antagonists & inhibitors ; Receptor, Anaphylatoxin C5a/genetics ; Receptor, Anaphylatoxin C5a/metabolism

Neutrophils are the most abundant white blood cells, with a vital role in innate immune defense against bacterial and fungal pathogens. Although mostly associated with pathological processes directly related to immune defense, they can also play a detrimental role in inflammatory conditions and have been found to have a pro-metastatic role in the spread of cancer cells. Here, we explore ways to temporarily suppress these detrimental activities. We first examined the possibility of using siRNA and antisense oligonucleotides (ASOs) for transient knockdown of the human and mouse C5a receptor, an important chemoattractant receptor involved in neutrophil-mediated injury that is associated with myocardial infarction, sepsis, and neurodegenerative diseases. We found that siRNAs and ASOs transfected into cultured cell lines can eliminate 70-90% of C5a receptor mRNA and protein within 72 h of administration, a clinically relevant time frame after a cardiovascular event. Targeted drug delivery to specific cells or tissues of interest in a mammalian host, however, remains a major challenge. Here, using phage display technology, we have identified peptides that bind specifically to CD177, a neutrophil-specific surface molecule. We have attached these peptides to fluorescent, lipid-based nanoparticles and confirmed targeting and delivery to cultured cells ectopically presenting either human or mouse CD177. In addition, we have shown peptide-nanoparticle binding specifically to neutrophils in human and mouse blood. We anticipate that these or related tagged nanoparticles may be therapeutically useful for delivery of siRNAs or ASOs to neutrophils for transient knockdown of pro-inflammatory proteins such as the C5a receptor.
Competing Interests: NanoValent Pharmaceuticals Inc. has no commercial interest in pursuing the materials that have resulted from this collaboration. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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0 (CD177 protein, human)
0 (GPI-Linked Proteins)
0 (Isoantigens)
0 (Oligonucleotides, Antisense)
0 (RNA, Small Interfering)
0 (Receptor, Anaphylatoxin C5a)
0 (Receptors, Cell Surface)
147336-22-9 (Green Fluorescent Proteins)

Date Created: 20180711 Date Completed: 20190122 Latest Revision: 20190122

20250114

PMC6039027

10.1371/journal.pone.0200444

29990379