Matrix Metalloproteinase‐9‐Responsive Surface Charge‐Reversible Nanocarrier to Enhance Endocytosis as Efficient Targeted Delivery System for Cancer Diagnosis and Therapy. Issue 9 (10th March 2021)

• Record Type: Journal Article
• Authors: Han, Qiu‐Ju; Lan, Xiao‐Tong; Wen, Ying; Zhang, Chuan‐Zeng; Cleary, Michael; Sayyed, Yasra; Huang, Guangdong; Tuo, Xiaoling; Yi, Long; Xi, Zhen; Li, Lu‐Yuan; Zhang, Qiang‐Zhe
• Is Part Of: Advanced healthcare materials. Volume 10:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-10
• Subjects: charge reversal -- cleavable peptides -- delivery platforms -- liposomes -- MMP9‐responsive peptides; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202002143
• Languages: English
• ISSNs: 2192-2640

Abstract

Abstract: Nanoparticles, that can be enriched in the tumor microenvironment and deliver the payloads into cancer cells, are desirable carriers for theranostic agents in cancer diagnosis and treatment. However, efficient targeted delivery and enhanced endocytosis for probes and drugs in theranostics are still major challenges. Here, a nanoparticle, which is capable of charge reversal from negative to positive in response to matrix metalloproteinase 9 (MMP9) in tumor microenvironment is reported. This nanoparticle is based on a novel charge reversible amphiphilic molecule consisting of hydrophobic oleic acid, MMP9‐cleavable peptide, and glutamate‐rich segment (named as OMPE). The OMPE‐modified cationic liposome forms an intelligent anionic nanohybrid (O‐NP) with enhanced endocytosis through surface charge reversal in response to MMP9 in vitro. Successfully, O‐NP nanohybrid performs preferential accumulation and enhances the endocytosis in MMP9‐expressing xenografted tumors in mouse models, which improve the sensitivity of diagnosis agents and the antitumor effects of drugs in vivo by overcoming their low solubility and/or nonspecific enrichment. These results indicate that O‐NP can be a promising delivery platform for cancer diagnosis and therapy. Abstract : Functional amphiphilic molecule (OMPE) consists of three motifs, hydrophobic oleic acid, MMP9‐responsive cleavable peptide connecting a glutamate‐rich segment. When encountered MMP9 overexpressed microenvironment, the negative charge of the polyglutamates motif of the OMPE is eliminated, thus the surface charge of the anionic nanocarrier (OMPE‐modified cationic nanoparticles, O‐NP) reverses to cationic resulting in facilitated endocytosis and targeted tumor theranostics.