Identifying a Membrane-Type 2 Matrix Metalloproteinase-Targeting Peptide for Human Lung Cancer Detection and Targeting Chemotherapy with Functionalized Mesoporous Silica

• Published in: ACS applied bio materials 2019-01, Vol.2 (1), p.397-405
• Main Authors: Ren, Li, Ma, Zheng, Li, Qinglan, Zhao, Weidong, Wang, Ye, Wang, Hongda, Shen, Liqiao, Zhang, Chengkai, Fang, Xuexun, Yu, Jihong
• Format: Article
• Language: English
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.8b00633

Membrane-type 2 matrix metalloproteinase (MT2-MMP) is critical for the aggressive lung tumor growth, progression, and metastasis. Here, to obtain the peptides in binding specifically to MT2-MMP, a phage-displayed 12 peptide library was used and the affinity of peptides toward MT2-MMP was identified by multitest methods. The results showed that a specific MT2-MMP-targeting peptide with the sequence of HHRLHSAPPPQA (MT2-AF5p) exhibited a high specificity and strong affinity against lung tumors. To further achieve specific targeting and precise therapeutic effects, MT2-AF5p was conjugated onto fluorescent mesoporous silica nanoparticles (FMSN-NH2) and loaded with doxorubicin (DOX) to construct a chemotherapeutic drug-targeting delivery system (DOX-loaded FMSN@MT2-AF5p). The DOX-loaded FMSN@MT2-AF5p achieved a boost in DOX release in an acidic environment. Most importantly, FMSN@MT2-AF5p efficiently targeted the tumor area, as seen in the fluorescent imaging ex vivo. The novel peptide-functionalized nanoparticles with a good biocompatibility are promising for clinical use as a precise targeting nanodrug for lung cancer diagnosis and therapy.