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.
In article number 2002143 by Qiang‐Zhe Zhang, Lu‐Yuan Li, and co‐workers, a novel MMP9‐catalyzed charge reversal nanoparticle (O‐NP) is developed for theranostic agents in cancer diagnosis and therapy. The O‐NP nanohybrid successfully performs preferential accumulation and enhances the endocytosis in MMP9‐expressing xenografted tumors by charge reversal from negative to positive in mouse models, which improves the sensitivity of diagnosis agents and the anti‐tumor effects of drugs in vivo by overcoming their low solubility and/or nonspecific enrichment.
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