title: Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.
abstract: Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p< 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems.
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Fataneh
authors.initials: F
authors.lastname: Karandish
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Manas K
authors.initials: MK
authors.lastname: Haldar
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Seungyong
authors.initials: S
authors.lastname: You
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Brooks
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Brooks
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Yongki
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Pharmaceutical Sciences and Department of Physics, North Dakota State University , 1401 Albrecht Blvd., Fargo, North Dakota 58102, United States.
authors.forename: Sanku
authors.initials: S
authors.lastname: Mallik