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Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer.
- Source :
-
Drug delivery [Drug Deliv] 2018 Nov; Vol. 25 (1), pp. 576-584. Date of Electronic Publication: 2018 Feb 20. - Publication Year :
- 2018
-
Abstract
- The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer.
- Subjects :
- Animals
Cell Line, Tumor
Chemokine CXCL1 biosynthesis
Chemokine CXCL1 genetics
Female
Gene Silencing drug effects
Gene Silencing physiology
Gene Transfer Techniques
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Ovarian Neoplasms genetics
Ovarian Neoplasms pathology
RNA, Small Interfering genetics
Xenograft Model Antitumor Assays
Antineoplastic Agents administration & dosage
Chemokine CXCL1 administration & dosage
Follicle Stimulating Hormone administration & dosage
Nanoparticles administration & dosage
Ovarian Neoplasms drug therapy
RNA, Small Interfering administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1521-0464
- Volume :
- 25
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Drug delivery
- Publication Type :
- Academic Journal
- Accession number :
- 29461120
- Full Text :
- https://doi.org/10.1080/10717544.2018.1440667