title: An ultra pH-sensitive and aptamer-equipped nanoscale drug-delivery system for selective killing of tumor cells.
abstract: Nanotechnology has often been applied in the development of targeted drug-delivery systems for the treatment of cancer. An ideal nanoscale system for drug delivery should be able to selectively deliver and rapidly release the carried therapeutic drug(s) in cancer cells and, more importantly, not react to off-target cells so as to eliminate unwanted toxicity on normal tissues. To reach this goal, a selective chemotherapeutic is formulated using a hollow gold nanosphere (HAuNS) equipped with a biomarker-specific aptamer (Apt), and loaded with the chemotherapy drug doxorubicin (DOX). The formed Apt-HAuNS-Dox, approximately 42 nm in diameter, specifically binds to lymphoma tumor cells and does not react to control cells that do not express the biomarker. Through aptamer-mediated selective cell binding, the Apt-HAuNS-Dox is internalized exclusively into the targeted tumor cells, and then released the DOX intracellularly. Of note, although the formed Apt-HAuNS-Dox is stable under normal biological conditions (pH 7.4), it appears ultrasensitive to pH change and rapidly releases 80% of the loaded DOX within 2 h at pH 5.0, a condition seen in cell lysosomes. Functional assays using cell mixtures show that the Apt-HAuNS-Dox selectively kills lymphoma tumor cells, but has no effect on the growth of the off-target cells in the same cultures, indicating that this ultra pH-sensitive Apt-HAuNS-Dox can selectively treat cancer through specific aptamer guidance, and will have minimal side effects on normal tissue.
authors.affiliation: Department of Pathology and Genomic Medicine, The Methodist Hospital and Cancer Pathology Laboratory, The Methodist Hospital Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
authors.forename: Nianxi
authors.initials: N
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: You
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zeng
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D054118:Nanospheres / Q000737:chemistry*; D009369:Neoplasms / Q000473:pathology*
chemical_list: D052157:Aptamers, Nucleotide; D014408:Biomarkers, Tumor; D006046:Gold; D004317:Doxorubicin
keywords: aptamers; drug delivery; hollow gold nanospheres; pH sensitive; targeted therapies