Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 9, Issue 29, Pages 24462-24475Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b05617
Keywords
EGFR; EGFRvIII; AE; D-peptide; multitargeted drug delivery; glioblastoma
Funding
- National Basic Research Program of China (973 Program) [2013CB932500]
- National Natural Science Foundation of China [81690263, 81473149]
- Shanghai International Science and Technology Cooperation project [16430723800]
- Development Project of Shanghai Peak Disciplines-Integrative Medicine [20150407]
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Tumor-homing peptides have been widely used to mediate active targeted drug delivery. L-AE is a reported targeting peptide demonstrating high binding affinity to epidermal growth factor receptor (EGFR) and mutation variant III (EGFRvIII) overexpressed on neovasculature, vasculogenic mimicry, tumor cells, and tumor stem cells. To improve its proteolytic stability, a D-peptide ligand (termed D-AE, the enantiomer of L-AE) was developed. D-AE was confirmed to bind receptors EGFR and EGFRvIII with targeting capability comparable to L-AE. In vivo biodistribution demonstrated the superiority of D-AE in prolonged circulation and enhanced intratumoral accumulation. Furthermore, stabilized peptide modification endowed micelles higher transcytosis efficiency and penetrating capability on blood-brain tumor barrier/U87 tumor spheroids coculture model. When paclitaxel (PTX) was loaded, D-AE-micelle/PTX demonstrated excellent antitumor effect in comparison to Taxol, micelle/PTX, and L-AE-micelle/PTX. These findings indicated that the multitargeted drug delivery system enabled by D-AE ligand provides a promising way for glioma therapy.
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