期刊
SIGNAL TRANSDUCTION AND TARGETED THERAPY
卷 5, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41392-020-0183-1
关键词
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资金
- National Nature Science Foundation of China [81672607, 81500077]
- National Key Specialty Construction Project of Clinical Pharmacy [30305030698]
- Nature Science Foundation of Beijing [7192143]
- Beijing Nova Program [Z171100001117115]
- Special Foundation for State Major Research Program of China [2016YFC0106603]
- Sichuan Provincial People's Hospital [2017LY08]
Although targeted therapy has been extensively investigated for breast cancers, a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers. Mammaglobin-A (Mam-A), which is overexpressed in most breast carcinomas, has been proposed as a promising target. However, the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study. Here, seven potential epitopes of Mam-A were disclosed, and a unique epitope was then identified in most types of breast cancers, despite the genotypic heterogeneity. With phage display technology, the epitope was determined to be N-terminal amino acids 42-51 of Mam-A (N42-51). Then, the N42-51 epitope-specific monoclonal antibody, mAb785, was conjugated to poly lactic-co-glycolic acid (PLGA) nanoparticles loaded with therapeutic agents, thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers. The computer simulation of the N42-51 epitope and the mAb785 structures, as well as their interactions, further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.
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