Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids

被引:28
作者
Karandish, Fataneh [1 ]
Haldar, Manas K. [1 ,4 ]
You, Seungyong [2 ]
Brooks, Amanda E. [1 ]
Brooks, Benjamin D. [1 ]
Guo, Bin [1 ,3 ]
Choi, Yongki [2 ]
Mallik, Sanku [1 ]
机构
[1] North Dakota State Univ, Dept Pharmaceut Sci, 1401 Albrecht Blvd, Fargo, ND 58102 USA
[2] North Dakota State Univ, Dept Phys, 1401 Albrecht Blvd, Fargo, ND 58102 USA
[3] Univ Houston, Dept Pharmaceut Sci, 3455 Cullen Blvd, Houston, TX 77204 USA
[4] Amer Radiolabeled Chem Inc, 101 ARC Dr, St Louis, MO 63146 USA
关键词
IN-VITRO; EMERGING PLATFORM; EXPRESSION; DOXORUBICIN; INHIBITOR; CULTURE; PSMA;
D O I
10.1021/acsomega.6b00126
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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 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.
引用
收藏
页码:952 / 962
页数:11
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