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Blood–Brain Barrier- and Blood–Brain Tumor Barrier-Penetrating Peptide-Derived Targeted Therapeutics for Glioma and Malignant Tumor Brain Metastases
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-10-29 , DOI: 10.1021/acsami.9b14046
Long Chen , Dan Zeng 1 , Nuo Xu , Chengpeng Li , Wenyuan Zhang , Xinjie Zhu , Yan Gao 1 , Peng R. Chen , Jian Lin
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2019-10-29 , DOI: 10.1021/acsami.9b14046
Long Chen , Dan Zeng 1 , Nuo Xu , Chengpeng Li , Wenyuan Zhang , Xinjie Zhu , Yan Gao 1 , Peng R. Chen , Jian Lin
Affiliation
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Glioma is the most common malignant tumor of the central nervous system (CNS). Therapeutic efficacy of glioma treatment is greatly limited by the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB), which restrict the passage of most drugs into the brain and tumors. Developing drug delivery systems that cross the BBB and BBTB will aid in the treatment of glioma and malignant brain metastases. One emerging solution is to identify peptide vectors that penetrate the BBB/BBTB. Herein, a novel BBB/BBTB-penetrating peptide was identified from the phage-displayed peptide library. Peptide–drug conjugates (PDCs) were derived and applied to treat glioma and breast cancer brain metastases. Antitumor activity was achieved in both tumor models with synergistic effects when combined with the currently used chemotherapy drug temozolomide. The peptide reported herein can serve as a universal vector for shuttling compounds across the BBB; therefore, it may have wide applications for treating brain tumors and other CNS diseases.
中文翻译：
血脑屏障和血脑肿瘤穿透肽的针对胶质瘤和恶性肿瘤脑转移的靶向治疗药物
胶质瘤是中枢神经系统（CNS）最常见的恶性肿瘤。胶质瘤的治疗功效受到血脑屏障（BBB）和血脑肿瘤屏障（BBTB）的极大限制，这限制了大多数药物进入大脑和肿瘤的通道。开发跨越BBB和BBTB的药物递送系统将有助于治疗神经胶质瘤和恶性脑转移。一种新兴的解决方案是鉴定穿透BBB / BBTB的肽载体。在此，从噬菌体展示的肽文库中鉴定出一种新型的穿透BBB / BBTB的肽。肽-药物结合物（PDC）衍生并用于治疗神经胶质瘤和乳腺癌的脑转移。当与当前使用的化疗药物替莫唑胺联用时，在两种肿瘤模型中均获得了具有协同作用的抗肿瘤活性。本文报道的肽可以用作穿梭于整个BBB中的化合物的通用载体。因此，它可能在治疗脑肿瘤和其他中枢神经系统疾病方面具有广泛的应用。
更新日期：2019-10-29
中文翻译：
血脑屏障和血脑肿瘤穿透肽的针对胶质瘤和恶性肿瘤脑转移的靶向治疗药物
胶质瘤是中枢神经系统（CNS）最常见的恶性肿瘤。胶质瘤的治疗功效受到血脑屏障（BBB）和血脑肿瘤屏障（BBTB）的极大限制，这限制了大多数药物进入大脑和肿瘤的通道。开发跨越BBB和BBTB的药物递送系统将有助于治疗神经胶质瘤和恶性脑转移。一种新兴的解决方案是鉴定穿透BBB / BBTB的肽载体。在此，从噬菌体展示的肽文库中鉴定出一种新型的穿透BBB / BBTB的肽。肽-药物结合物（PDC）衍生并用于治疗神经胶质瘤和乳腺癌的脑转移。当与当前使用的化疗药物替莫唑胺联用时，在两种肿瘤模型中均获得了具有协同作用的抗肿瘤活性。本文报道的肽可以用作穿梭于整个BBB中的化合物的通用载体。因此，它可能在治疗脑肿瘤和其他中枢神经系统疾病方面具有广泛的应用。
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