Nanoparticle-Based Follistatin Messenger RNA Therapy for Reprogramming Metastatic Ovarian Cancer and Ameliorating Cancer-Associated Cachexia.
| Title: | Nanoparticle-Based Follistatin Messenger RNA Therapy for Reprogramming Metastatic Ovarian Cancer and Ameliorating Cancer-Associated Cachexia. |
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| Authors: | Korzun T; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Department of Biomedical Engineering, Oregon Health & Science University, 3303 SW Bond Avenue, Portland, OR, 97239, USA.; Medical Scientist Training Program, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Moses AS; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Kim J; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Patel S; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Schumann C; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Levasseur PR; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Diba P; Medical Scientist Training Program, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Olson B; Medical Scientist Training Program, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Rebola KGO; Knight Cancer Institute, Oregon Health & Science University, 2720 S Moody Avenue, Portland, OR, 97201, USA.; Norgard M; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Park Y; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Demessie AA; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Eygeris Y; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Grigoriev V; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Sundaram S; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Pejovic T; Departments of Obstetrics and Gynecology and Pathology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA.; Brody JR; Knight Cancer Institute, Oregon Health & Science University, 2720 S Moody Avenue, Portland, OR, 97201, USA.; Taratula OR; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Zhu X; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Sahay G; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Marks DL; Papé Family Pediatric Research Institute, Oregon Health & Science University, SW Sam Jackson Park Rd, Mail Code L481, Portland, OR, 97239, USA.; Knight Cancer Institute, Oregon Health & Science University, 2720 S Moody Avenue, Portland, OR, 97201, USA.; Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Taratula O; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 S Moody Avenue, Portland, OR, 97201, USA.; Department of Biomedical Engineering, Oregon Health & Science University, 3303 SW Bond Avenue, Portland, OR, 97239, USA. |
| Source: | Small (Weinheim an der Bergstrasse, Germany) [Small] 2022 Nov; Vol. 18 (44), pp. e2204436. Date of Electronic Publication: 2022 Sep 13. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 101235338 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1613-6829 (Electronic) Linking ISSN: 16136810 NLM ISO Abbreviation: Small Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Weinheim, Germany : Wiley-VCH, c2005- |
| MeSH Terms: | Ovarian Neoplasms*/complications ; Ovarian Neoplasms*/therapy ; Nanoparticles*; Cachexia/drug therapy ; Cachexia/metabolism ; Follistatin/metabolism ; Follistatin/pharmacology ; Follistatin/therapeutic use ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Muscular Atrophy/genetics ; Muscular Atrophy/metabolism ; Muscular Atrophy/pathology ; Muscle, Skeletal/metabolism ; Humans ; Female ; Liposomes |
| Abstract: | This study presents the first messenger RNA (mRNA) therapy for metastatic ovarian cancer and cachexia-induced muscle wasting based on lipid nanoparticles that deliver follistatin (FST) mRNA predominantly to cancer clusters following intraperitoneal administration. The secreted FST protein, endogenously synthesized from delivered mRNA, efficiently reduces elevated activin A levels associated with aggressive ovarian cancer and associated cachexia. By altering the cancer cell phenotype, mRNA treatment prevents malignant ascites, delays cancer progression, induces the formation of solid tumors, and preserves muscle mass in cancer-bearing mice by inhibiting negative regulators of muscle mass. Finally, mRNA therapy provides synergistic effects in combination with cisplatin, increasing the survival of mice and counteracting muscle atrophy induced by chemotherapy and cancer-associated cachexia. The treated mice develop few nonadherent tumors that are easily resected from the peritoneum. Clinically, this nanomedicine-based mRNA therapy can facilitate complete cytoreduction, target resistance, improve resilience during aggressive chemotherapy, and improve survival in advanced ovarian cancer.; (© 2022 Wiley-VCH GmbH.) |
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| Grant Information: | R01 CA237569 United States CA NCI NIH HHS; R37 CA234006 United States CA NCI NIH HHS |
| Contributed Indexing: | Keywords: cachexia; lipid nanoparticles; mRNA therapy; muscle atrophy; ovarian cancer |
| Substance Nomenclature: | 0 (Follistatin); 0 (RNA, Messenger); 0 (Lipid Nanoparticles); 0 (Liposomes) |
| Entry Date(s): | Date Created: 20220913 Date Completed: 20221107 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9633376 |
| DOI: | 10.1002/smll.202204436 |
| PMID: | 36098251 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't