Liposomal delivery of dexamethasone attenuates prostate cancer bone metastatic tumor growth in vivo.
Liposomal delivery of dexamethasone attenuates prostate cancer bone metastatic tumor growth in vivo.
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DOI：
10.1002/pros.22963
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发表时间：
2015-06
期刊：
影响因子：
2.8
通讯作者：
Metselaar, Josbert M.
中科院分区：
文献类型：
--
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.
炎性肿瘤微环境，更具体地说是肿瘤相关巨噬细胞，在前列腺癌向转移性骨疾病的发展和进展中起着至关重要的作用。肿瘤通常以渗漏的血管系统为特征，结合脂质体的延长循环动力学，通过所谓的增强渗透性和保留（EPR）效应，导致这些药物载体的有效肿瘤定位。在这项研究中，我们评估了在前列腺癌骨转移模型中糖皮质激素地塞米松的靶向脂质体药物递送的效用。用0.2-1.0-5.0 mg/kg/周游离DEX和脂质体DEX静脉内处理荷瘤Balb-c nu/nu小鼠3-4周，并通过生物发光成像监测肿瘤生长。体内注射给药的脂质体有效地定位于骨转移，并且用（脂质体）地塞米松治疗已建立的骨转移导致在治疗开始后长达26天的肿瘤生长的显著抑制。此外，1.0 mg/kg地塞米松脂质体显著优于1.0 mg/kg游离地塞米松，并且发现在临床相关剂量下耐受良好，显示出强效抗肿瘤疗效。糖皮质激素地塞米松的脂质体递送抑制恶性骨病变的生长。我们认为地塞米松脂质体包封为晚期转移性前列腺癌提供了一种有希望的新治疗选择，支持进一步的临床评价。前列腺75：815-824，2015年。版权所有© 2015作者.《前列腺》，由Wiley Periodicals，Inc.出版。
The inflammatory tumor microenvironment, and more specifically the tumor‐associated macrophages, plays an essential role in the development and progression of prostate cancer towards metastatic bone disease. Tumors are often characterized by a leaky vasculature, which ‐ combined with the prolonged circulation kinetics of liposomes ‐ leads to efficient tumor localization of these drug carriers, via the so‐called enhanced permeability and retention (EPR) ‐effect. In this study, we evaluated the utility of targeted, liposomal drug delivery of the glucocorticoid dexamethasone in a model of prostate cancer bone metastases. Tumor‐bearing Balb‐c nu/nu mice were treated intravenously with 0.2–1.0–5.0 mg/kg/week free‐ and liposomal DEX for 3–4 weeks and tumor growth was monitored by bioluminescent imaging. Intravenously administered liposomes localize efficiently to bone metastases in vivo and treatment of established bone metastases with (liposomal) dexamethasone resulted in a significant inhibition of tumor growth up to 26 days after initiation of treatment. Furthermore, 1.0 mg/kg liposomal dexamethasone significantly outperformed 1.0 mg/kg free dexamethasone, and was found to be well‐tolerated at clinically‐relevant dosages that display potent anti‐tumor efficacy. Liposomal delivery of the glucocorticoid dexamethasone inhibits the growth of malignant bone lesions. We believe that liposomal encapsulation of dexamethasone offers a promising new treatment option for advanced, metastatic prostate cancer which supports further clinical evaluation. Prostate 75: 815–824, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.
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作者：
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