Thermally targeted delivery of a c-Myc inhibitory polypeptide inhibits tumor progression and extends survival in a rat glioma model.
Thermally targeted delivery of a c-Myc inhibitory polypeptide inhibits tumor progression and extends survival in a rat glioma model.
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DOI：
10.1371/journal.pone.0055104
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Raucher D
中科院分区：
文献类型：
--
作者：
Bidwell GL 3rd;Perkins E;Hughes J;Khan M;James JR;Raucher D
胶质母细胞瘤的治疗因肿瘤对化疗的高耐药性、药物穿过血脑屏障的渗透性差以及化疗和放疗对正常神经组织的破坏作用而变得复杂。为了克服这些限制，开发了一种热响应多肽，用于使用聚焦热疗将治疗肽靶向递送至脑肿瘤。肽载体基于类弹性蛋白多肽（ELP），它是一种热响应生物聚合物，在高于特征转变温度时形成聚集体。 ELP 使用细胞穿透肽 (CPP) 进行修饰，以增强向脑肿瘤的递送并介导跨肿瘤细胞质膜的摄取，并使用 c-Myc (H1) 肽抑制剂进行修饰。在患有脑内神经胶质瘤的大鼠中，全身给药后 ELP 的脑肿瘤靶向性通过使用 CPP 增强了 5 倍。当主要的 CPP-ELP 融合 c-Myc 抑制剂与肿瘤的集中热疗相结合时，观察到肿瘤多肽水平额外增加 3 倍，肿瘤体积减少 80%，延迟肿瘤相关神经功能缺损的发生，并且中位生存时间至少加倍，包括 80% 的动物完全消退。这项工作表明 c-Myc 抑制肽可以有效地递送至脑肿瘤。
Treatment of glioblastoma is complicated by the tumors’ high resistance to chemotherapy, poor penetration of drugs across the blood brain barrier, and damaging effects of chemotherapy and radiation to normal neural tissue. To overcome these limitations, a thermally responsive polypeptide was developed for targeted delivery of therapeutic peptides to brain tumors using focused hyperthermia. The peptide carrier is based on elastin-like polypeptide (ELP), which is a thermally responsive biopolymer that forms aggregates above a characteristic transition temperature. ELP was modified with cell penetrating peptides (CPPs) to enhance delivery to brain tumors and mediate uptake across the tumor cells’ plasma membranes and with a peptide inhibitor of c-Myc (H1). In rats with intracerebral gliomas, brain tumor targeting of ELP following systemic administration was enhanced up to 5-fold by the use of CPPs. When the lead CPP-ELP-fused c-Myc inhibitor was combined with focused hyperthermia of the tumors, an additional 3 fold increase in tumor polypeptide levels was observed, and 80% reduction in tumor volume, delayed onset of tumor-associated neurological deficits, and at least doubled median survival time including complete regression in 80% of animals was achieved. This work demonstrates that a c-Myc inhibitory peptide can be effectively delivered to brain tumors.
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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