【摘 要】
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Effective delivery of probes and drugs to tumor cells remains major challenge for cancer diagnosis and treatment.Nanoparticles capable of escaping the reticuloendothelial system while improving endocy
【机 构】
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State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy,and Tianjin Key Laborator
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Effective delivery of probes and drugs to tumor cells remains major challenge for cancer diagnosis and treatment.Nanoparticles capable of escaping the reticuloendothelial system while improving endocytosis of the payload are promising strategies.Compared to anionic counter-parts,cationic PEGylated nanoparticles outperform in inhibiting tumor growth,but show inferior in blood circulation time and tumor accumulation.[1,2] Here,we report an intelligent nano carrier able to reverse its negative surface charge to positive in tumor microenvironment via response to matrix metalloprotein 9(MMP9).Briefly,functional amphiphilic molecule is charge reversible,which consists of three motifs,oleic acid as hydrophobic segment,MMP9 switchable peptide sequence connecting a glutamate-rich segment(OMPE).OMPE modified cationic nanoparticles(O-NP)form an intelligent anionic nano-hybrid.Once O-NP was accumulated at tumors with MMP9 high expression,anionic O-NP reversed to cationic vehicle.O-NP takes advantage of the stability of anionic nanoparticles in blood circulation and tumor accumulation,while the ability of enhanced endocytosis of cationic nanoparticles in tumor sites.Successfully,O-NP enhances the anti-tumor effects and overcome the solubility and nonspecific enrichment of small molecules.We envisioned that O-NP would be a promising nanocarrier for cancer diagnosis and therapeutics.
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