Polyethylene glycol-polylactic acid nanoparticles modified with cysteine-arginine-glutamic acid-lysine-alanine fibrin-homing peptide for glioblastoma therapy by enhanced retention effect.
Polyethylene glycol-polylactic acid nanoparticles modified with cysteine-arginine-glutamic acid-lysine-alanine fibrin-homing peptide for glioblastoma therapy by enhanced retention effect.
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半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸纤维蛋白归巢肽修饰的聚乙二醇-聚乳酸纳米颗粒通过增强保留效应用于胶质母细胞瘤治疗
DOI：
10.2147/ijn.s72649
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发表时间：
2014
影响因子：
8
通讯作者：
Pang Z
中科院分区：
文献类型：
--
作者：
Wu J;Zhao J;Zhang B;Qian Y;Gao H;Yu Y;Wei Y;Yang Z;Jiang X;Pang Z
对于纳米颗粒给药系统，脑胶质母细胞瘤治疗的关键挑战是其在胶质母细胞瘤实质中的渗透和保留较差。作为许多实体瘤的细胞外基质中的主要组分，纤维蛋白在胶质母细胞瘤形态和胶质母细胞瘤细胞分化和增殖的维持中起关键作用。我们通过将聚乙二醇-聚乳酸纳米颗粒（NPs）与半胱氨酸-精氨酸-谷氨酸-赖氨酸-丙氨酸（CREKA; TNP）（一种对纤维蛋白具有特殊亲和力的肽）缀合，开发了一种新的药物递送系统，以介导胶质母细胞瘤归巢并延长NP在肿瘤部位的滞留。体外结合试验表明，CREKA显着增强与纤维蛋白的NPs的特异性结合。携带胶质母细胞瘤的裸鼠的体内荧光成像、离体脑成像和胶质母细胞瘤分布表明，与未修饰的NP相比，TNP在胶质母细胞瘤部位具有更高的积累和更长的保留。此外，药效学结果表明，紫杉醇负载的TNP显着延长颅内U87胶质母细胞瘤荷瘤裸鼠的中位生存时间与对照组相比，紫杉醇，和NP。这些发现表明TNP能够靶向胶质母细胞瘤并增强保留，这是肿瘤治疗的有价值的策略。
For a nanoparticulate drug-delivery system, crucial challenges in brain-glioblastoma therapy are its poor penetration and retention in the glioblastoma parenchyma. As a prevailing component in the extracellular matrix of many solid tumors, fibrin plays a critical role in the maintenance of glioblastoma morphology and glioblastoma cell differentiation and proliferation. We developed a new drug-delivery system by conjugating polyethylene glycol–polylactic acid nanoparticles (NPs) with cysteine–arginine–glutamic acid–lysine–alanine (CREKA; TNPs), a peptide with special affinity for fibrin, to mediate glioblastoma-homing and prolong NP retention at the tumor site. In vitro binding tests indicated that CREKA significantly enhanced specific binding of NPs with fibrin. In vivo fluorescence imaging of glioblastoma-bearing nude mice, ex vivo brain imaging, and glioblastoma distribution demonstrated that TNPs had higher accumulation and longer retention in the glioblastoma site over unmodified NPs. Furthermore, pharmacodynamic results showed that paclitaxel-loaded TNPs significantly prolonged the median survival time of intracranial U87 glioblastoma-bearing nude mice compared with controls, Taxol, and NPs. These findings suggested that TNPs were able to target the glioblastoma and enhance retention, which is a valuable strategy for tumor therapy.