Статья

Stabilized Heptapeptide A7R for Enhanced Multifunctional Liposome-Based Tumor-Targeted Drug Delivery

Ying ManDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, ChinaQing ShenDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, ChinaYu LiuDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, ChinaZhiqiang YanInstitute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of chemistry and molecular engineering, East China Normal University, Shanghai 200062, ChinaXiaoli WeiDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, ChinaChangyou ZhanDepartment of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, ChinaJie GaoDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, ChinaCao XieDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, ChinaBingxin YaoDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, ChinaWeiyue LuDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, (Fudan University), Ministry of Education, Shanghai 201203, China

2016en

ABI

Аннотация

(L)A7R (ATWLPPR) is a heptapeptide with high binding affinity in vitro to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed on glioma, glioma vasculogenic mimicry and neovasculature. However, its tumor targeting efficacy is significantly reduced in vivo due to proteolysis in blood circulation. To improve the in vivo stability and targeting efficacy, the retro inverso isomer of (L)A7R ((D)A7R) was developed for glioma-targeted drug delivery. (D)A7R was expected to have a similar binding affinity to its receptors in vitro (VEGFR2 and NRP-1), which was experimentally confirmed. In vivo, (D)A7R-modified liposomes achieved improved glioma-targeted efficiency than did (L)A7R-modified liposomes. After loading a chemotherapeutic agent (doxorubicin), (D)A7R-modified liposomes significantly inhibited subcutaneous model tumor in comparison to free doxorubicin, plain liposomes and (L)A7R-modified liposomes. In summary, the present study presented the potential of a proteolytically stable d-peptide ligand for in vivo tumor-targeted drug delivery.

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Идентификаторы

DOI: 10.1021/acsami.6b01300

Цитирования и источники

Цитирований: 2Использованных источников: 0

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