Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.
Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.
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DOI：
10.1021/acsomega.6b00126
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发表时间：
2016-11-30
期刊：
影响因子：
4.1
通讯作者：
Mallik, Sanku
中科院分区：
文献类型：
--
作者：
Karandish, Fataneh;Haldar, Manas K.;You, Seungyong;Brooks, Amanda E.;Brooks, Benjamin D.;Guo, Bin;Choi, Yongki;Mallik, Sanku
前列腺癌细胞在表面上过表达前列腺特异性膜抗原（PSMA）受体。靶向PSMA受体为药物递送创造了独特的机会。多西他赛是食品和药物管理局批准的用于治疗转移性和雄激素非依赖性前列腺癌的药物，而莫西司他是I类组蛋白脱乙酰酶的有效抑制剂。在这项研究中，我们制备了还原敏感的聚合物囊泡，在表面上呈现叶酸，并封装多西他赛或mocetinostat。叶酸的存在允许PSMA受体的有效靶向和随后在培养的LNCaP前列腺癌细胞球状体中聚合物囊泡的内化。细胞内还原剂有效地从聚合物囊泡释放多西他赛和mocetinostat。两种药物包封的聚合物囊泡制剂的组合显著（p < 0.05）降低了三维球状体培养物中LNCaP细胞的活力（与游离药物或对照相比）。计算出的联合指数值表明mocetinostat和多西他赛联合使用具有协同作用。因此，我们的PSMA靶向药物包封的聚合物囊泡有可能导致前列腺癌治疗的新方向，降低毒性并增加药物递送系统的功效。
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.
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影响因子：
2.8
作者：
Kroon, Jan;Buijs, Jeroen T.;van der Horst, Geertje;Cheung, Henry;van der Mark, Maaike;van Bloois, Louis;Rizzo, Larissa Y.;Lammers, Twan;Pelger, Rob C.;Storm, Gert;van der Pluijm, Gabri;Metselaar, Josbert M.
通讯作者：
Metselaar, Josbert M.
影响因子：
16
作者：
Xu, Xian;Farach-Carson, Mary C.;Jia, Xinqiao
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254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
DOI：
10.1016/1078-1439(95)00002-y
发表时间：
1995-01-01
期刊：
Urologic oncology
影响因子：
--
作者：
Wright, G L Jr;Haley, C;Schellhammer, P F
通讯作者：
Schellhammer, P F
影响因子：
11.2
作者：
Farokhzad, OC;Jon, SY;Langer, R
通讯作者：
Langer, R