Principal Investigator

Awardee Organization

Oregon State University
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Novel Nanomedicine-Based Therapeutic Approach For Treatment of Cancer Cachexia

Cachexia is a debilitating syndrome that occurs in numerous diseases including cancer and is characterized by a significant loss of skeletal muscle mass (with or without fat loss) that cannot be reversed by nutritional support. It most commonly occurs in gastric (85% of patients), pancreatic (83%) and lung (61%) cancers and up to 30% of deaths in these patient populations are attributable to cachexia alone. The numerous clinical trials confirmed that wasting of skeletal muscle mass is the hallmark of cachexia and it is responsible for shorter survival, poor treatment outcomes, increased toxicity to chemotherapy, post-operative complications, and physical impairment. Despite all efforts, there are currently no effective therapies to prevent muscle wasting in cachectic patients. A multidisciplinary team of investigators with complementary expertise in drug delivery, gene therapy, and cancer cachexia will develop an effective treatment for cachexia-associated muscle wasting. It will be based on polymeric nanoparticles specifically designed to deliver follistatin messenger RNA (mRNA) to the liver cells after systemic administration. The delivered mRNA will direct the cellular machinery of the liver cells to produce follistatin, a secreted glycoprotein that is capable of increasing lean muscle mass through inhibition of myostatin and Activin A. The last two are growth differentiation factors whose serum concentrations are increased in cachectic states, and they play a critical role in negatively regulating muscle mass. The research team has already developed mRNA-loaded nanoplatform that is non-toxic and elevates serum levels of follistatin protein within 8 h after subcutaneous injection. Wild-type mice that were treated with the nanoplatform exhibited significant increases in lean body mass. To further advance this technology, the goals are: (i) to enhance the delivery of the already developed nanoparticles to the liver, (ii) to evaluate delivery efficiency of the nanoparticles in mice with the humanized liver, and (iii) to validate therapeutic efficacy of the nanoparticles in novel murine pancreatic ductal adenocarcinoma (PDAC) and lung cancer models that exhibit all the hallmark features of human cachexia. These goals will be addressed with the following Specific Aims: 1 Evaluate the efficiency of mRNA-loaded nanoparticles following intravenous administration. 2. Test nanoplatform in mice with the humanized liver. 3. Determine whether nanoparticle-mediated delivery of follistatin mRNA attenuates cachexia in mouse models of PDAC and lung cancer. At the completion of this project, the research team will produce strong evidence that the proposed therapy will preserve muscle mass and attenuate other features of cachexia in mice with pancreatic and lung cancers. The long-term impact of this project is the successful application of the novel treatment in medical practice to sufficiently limit death and suffering from various cancers including lung and pancreatic cancers.


  • Esfandiari Nazzaro E, Sabei FY, Vogel WK, Nazari M, Nicholson KS, Gafken PR, Taratula O, Taratula O, Davare MA, Leid M. Discovery and Validation of a Compound to Target Ewing's Sarcoma. Pharmaceutics. 2021 Sep 24;13. (10). PMID: 34683845
  • Olson B, Marks DL, Grossberg AJ. Diverging metabolic programmes and behaviours during states of starvation, protein malnutrition, and cachexia. Journal of cachexia, sarcopenia and muscle. 2020 Dec;11(6):1429-1446. Epub 2020 Sep 28. PMID: 32985801
  • Park Y, Moses AS, Demessie AA, Singh P, Lee H, Korzun T, Taratula OR, Alani AWG, Taratula O. Poly(aspartic acid)-Based Polymeric Nanoparticle for Local and Systemic mRNA Delivery. Molecular pharmaceutics. 2022 Dec 5;19(12):4696-4704. Epub 2022 Nov 21. PMID: 36409995
  • Korzun T, Moses AS, Kim J, Patel S, Schumann C, Levasseur PR, Diba P, Olson B, Rebola KGO, Norgard M, Park Y, Demessie AA, Eygeris Y, Grigoriev V, Sundaram S, Pejovic T, Brody JR, Taratula OR, Zhu X, Sahay G, Marks DL, Taratula O. Nanoparticle-Based Follistatin Messenger RNA Therapy for Reprogramming Metastatic Ovarian Cancer and Ameliorating Cancer-Associated Cachexia. Small (Weinheim an der Bergstrasse, Germany). 2022 Nov;18(44):e2204436. Epub 2022 Sep 13. PMID: 36098251
  • Demessie AA, Park Y, Singh P, Moses AS, Korzun T, Sabei FY, Albarqi HA, Campos L, Wyatt CR, Farsad K, Dhagat P, Sun C, Taratula OR, Taratula O. An Advanced Thermal Decomposition Method to Produce Magnetic Nanoparticles with Ultrahigh Heating Efficiency for Systemic Magnetic Hyperthermia. Small methods. 2022 Dec;6(12):e2200916. Epub 2022 Nov 1. PMID: 36319445
  • Majumder J, Taratula O, Minko T. Nanocarrier-based systems for targeted and site specific therapeutic delivery. Advanced drug delivery reviews. 2019 Apr;144:57-77. Epub 2019 Aug 7. PMID: 31400350
  • Shah VM, Sheppard BC, Sears RC, Alani AW. Hypoxia: Friend or Foe for drug delivery in Pancreatic Cancer. Cancer letters. 2020 Nov 1;492:63-70. Epub 2020 Aug 18. PMID: 32822815
  • Sabei FY, Taratula O, Albarqi HA, Al-Fatease AM, Moses AS, Demessie AA, Park Y, Vogel WK, Esfandiari Nazzaro E, Davare MA, Alani A, Leid M, Taratula O. A targeted combinatorial therapy for Ewing's sarcoma. Nanomedicine : nanotechnology, biology, and medicine. 2021 Oct;37:102446. Epub 2021 Jul 23. PMID: 34303840
  • Ahoulou EO, Drinkard KK, Basnet K, St Lorenz A, Taratula O, Henary M, Grant KB. DNA Photocleavage in the Near-Infrared Wavelength Range by 2-Quinolinium Dicarbocyanine Dyes. Molecules (Basel, Switzerland). 2020 Jun 25;25. (12). PMID: 32630496
  • Garbuzenko OB, Kuzmov A, Taratula O, Pine SR, Minko T. Strategy to enhance lung cancer treatment by five essential elements: inhalation delivery, nanotechnology, tumor-receptor targeting, chemo- and gene therapy. Theranostics. 2019 Oct 22;9(26):8362-8376. doi: 10.7150/thno.39816. eCollection 2019. PMID: 31754402
  • Grossberg AJ, Chu LC, Deig CR, Fishman EK, Hwang WL, Maitra A, Marks DL, Mehta A, Nabavizadeh N, Simeone DM, Weekes CD, Thomas CR Jr. Multidisciplinary standards of care and recent progress in pancreatic ductal adenocarcinoma. CA: a cancer journal for clinicians. 2020 Sep;70(5):375-403. Epub 2020 Jul 19. PMID: 32683683
  • Moses AS, Demessie AA, Taratula O, Korzun T, Slayden OD, Taratula O. Nanomedicines for Endometriosis: Lessons Learned from Cancer Research. Small (Weinheim an der Bergstrasse, Germany). 2021 Feb;17(7):e2004975. Epub 2021 Jan 25. PMID: 33491876
  • Albarqi HA, Demessie AA, Sabei FY, Moses AS, Hansen MN, Dhagat P, Taratula OR, Taratula O. Systemically Delivered Magnetic Hyperthermia for Prostate Cancer Treatment. Pharmaceutics. 2020 Oct 25;12. (11). PMID: 33113767
  • Basnet K, Fatemipouya T, St Lorenz A, Nguyen M, Taratula O, Henary M, Grant KB. Single photon DNA photocleavage at 830 nm by quinoline dicarbocyanine dyes. Chemical communications (Cambridge, England). 2019 Oct 17;55(84):12667-12670. PMID: 31584046
  • St Lorenz A, Moses AS, Mamnoon B, Demessie AA, Park Y, Singh P, Taratula O, Taratula OR. A Photoacoustic Contrast Nanoagent with a Distinct Spectral Signature for Ovarian Cancer Management. Advanced healthcare materials. 2022 Dec 10: e2202946. Epub 2022 Dec 10. PMID: 36495088
  • Park Y, Demessie AA, Luo A, Taratula OR, Moses AS, Do P, Campos L, Jahangiri Y, Wyatt CR, Albarqi HA, Farsad K, Slayden OD, Taratula O. Targeted Nanoparticles with High Heating Efficiency for the Treatment of Endometriosis with Systemically Delivered Magnetic Hyperthermia. Small (Weinheim an der Bergstrasse, Germany). 2022 Jun;18(24):e2107808. Epub 2022 Apr 17. PMID: 35434932