title: Enzyme-responsive cell-penetrating peptide conjugated mesoporous silica quantum dot nanocarriers for controlled release of nucleus-targeted drug molecules and real-time intracellular fluorescence imaging of tumor cells.
abstract: Here, a set of novel and personalized nanocarriers are presented for controlled nucleus-targeted antitumor drug delivery and real-time imaging of intracellular drug molecule trafficking by integrating an enzyme activatable cell penetrating peptide (CPP) with mesoporous silica coated quantum dots nanoparticles. Upon loading of antitumor drug, doxorubicin (DOX) and further exposure to proteases in tumor cell environment, the enzymatic cleavage of peptide sequence activates oligocationic TAT residues on the QDs@mSiO2 surface and direct the DOX delivery into cellular nucleus. The systematic cell imaging and cytotoxicity studies confirm that the enzyme responsive DOX-loaded CPP-QDs@mSiO2 nanoparticles can selectively release DOX in the tumor cells with high cathepsin B enzyme expression and greatly facilitate DOX accumulation in targeted nucleus, thus exhibiting enhanced antitumor activity in these cells. As contrast, there is limited nuclear-targeted drug accumulation and lower tumor cytotoxicity observed in the cells without enzyme expression. More importantly, significant antitumor DOX accumulation and higher tumor inactivation is also found in the drug resistant tumor cells with targeted enzyme expression. Such simple and specific enzyme responsive mesoporous silica-QDs nanoconjugates provide great promise for rational design of targeted drug delivery into biological system, and may thus greatly facilitate the medical theranostics in the near future.
authors.affiliation: Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.
authors.forename: Jinming
authors.initials: J
authors.lastname: Li
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Shao
authors.forename: Yuanzeng
authors.initials: Y
authors.lastname: Min
authors.forename: Marianne
authors.initials: M
authors.lastname: Costa
authors.forename: Edwin K L
authors.initials: EK
authors.lastname: Yeow
authors.forename: Bengang
authors.initials: B
authors.lastname: Xing
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D041681:NIH 3T3 Cells; D016062:Porosity; D045663:Quantum Dots / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D012822:Silicon Dioxide; D004317:Doxorubicin; D002401:Cathepsin B
keywords: cell-penetrating peptides; enzyme responsive; intracellular imaging; mesoporous quantum dots; nucleus-targeted delivery