Solid tumor penetration by integrin-mediated pegylated poly(trimethylene carbonate) nanoparticles loaded with paclitaxel
Solid tumor penetration by integrin-mediated pegylated poly(trimethylene carbonate) nanoparticles loaded with paclitaxel
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DOI：
10.1016/j.biomaterials.2012.11.016
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发表时间：
2013-02-01
期刊：
影响因子：
14
通讯作者：
Fang, Xiaoling
中科院分区：
文献类型：
--
作者：
Jiang, Xinyi;Xin, Hongliang;Fang, Xiaoling
化疗药物的有限渗透是许多实体瘤化疗失败的原因之一。为了增强药物渗透到实体癌中，特别是渗透到肿瘤内的无血管区域中，我们提出了环状RGD肽功能化的聚乙二醇化聚（三亚甲基碳酸酯）纳米颗粒（c（RGDyK）-NP）。通过整合素介导的转胞吞作用和增强的药物渗透，c（RGDyK）-NP可以到达远离血管的肿瘤细胞，从而避免这些肿瘤细胞的癌症再生能力。在本研究中，在离体3D肿瘤球体和皮下异种移植小鼠模型上评价了实体瘤渗透、归巢、特异性和抗癌功效。与传统的纳米粒（NP/PTX）和紫杉醇相比，c（RGDyK）-NP/PTX显示出最强的渗透和积聚到3D肿瘤球体中，在体内具有显著的肿瘤归巢特异性，并且在体外和体内具有最大的肿瘤生长抑制作用。组织化学分析显示，静脉给予治疗剂量后，在主要器官中未观察到明显的组织病理学异常或病变。总之，环RGD肽缀合的PEG-PTMC纳米颗粒可以促进药物在肿瘤组织中的渗透和积聚，并且可能是一种有前途的用于增强实体癌的化疗的载体。(C)2012爱思唯尔有限公司保留所有权利。
Limited penetration of antineoplastic agents is one of the contributing factors for chemotherapy failure of many solid tumors. In order to enhance drug penetration into solid cancer, especially, into the avascular regions inside tumors, we proposed cyclic RGD peptide functionalized PEGylated poly(trimethylene carbonate) nanoparticles (c(RGDyK)-NP). By integrin-mediated transcytosis and enhanced drug permeation, c(RGDyK)-NP could access the neoplastic cells distant from blood vessels, and consequently, avoiding the capability of cancer regeneration from these tumor cells. In the present study, the solid tumor penetration, homing,specificity and anticancer efficacy were evaluated both on the ex vivo 3D tumor spheroids and on the subcutaneous xenograft mice model. In comparison with conventional nanoparticles (NP/PTX) and Taxol, c(RGDyK)-NP/PTX showed the strongest penetration and accumulation into 3D tumor spheroids, a marked tumor-homing specificity in vivo and the greatest tumor growth inhibitory effect in vitro and in vivo. Histochemistry analysis revealed that no obvious histopathological abnormalities or lesions were observed in major organs after intravenous administration with the treatment doses. In conclusion, cyclic RGD peptide-conjugated PEG-PTMC nanoparticle could facilitate drug penetration and accumulation in tumor tissues and may be a promising vehicle for enhancing the chemotherapy of solid cancers. (C) 2012 Elsevier Ltd. All rights reserved.