title: Double targeting, controlled release and reversible delivery of daunorubicin to cancer cells by polyvalent aptamers-modified gold nanoparticles.
abstract: Clinical use of daunorubicin (Dau) in treatment of leukemia has been restricted because of its cardiotoxicity. Targeted delivery of anticancer drugs could decrease their off-target effects and enhance their efficacy. In this study a modified polyvalent aptamers (PA)-Daunorubicin (Dau)-Gold nanoparticles (AuNPs) complex was designed and its efficacy was assessed in Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Dau was efficiently loaded (10.5 μM) onto 1mL of PA-modified AuNPs. Dau was released from the PA-Dau-AuNPs complex in a pH-sensitive manner (faster release at pH5.5). The results of flow cytometry analysis indicated that the PA-Dau-AuNPs complex was efficiently internalized into target cells, but not into nontarget cells. The results of MTT assay were consistent with the internalization data. PA-Dau-AuNPs complex had less cytotoxicity in U266 cells compared to Dau alone and even Apt-Dau-AuNPs complex. The PA-Dau-AuNPs complex had more cytotoxicity in Molt-4 cells compared to Dau alone and even Apt-Dau-AuNPs complex. Cytotoxicity of PA-Dau-AuNPs complex was effectively antagonized using antisense of polyvalent aptamers. In conclusion, the designed drug delivery system inherited the properties of efficient drug loading, tumor targeting, pH-dependent drug release and controllable delivery of Dau to tumor cells.
authors.affiliation: Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Taghdisi
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Research Institute of Sciences and New Technology, Mashhad, Iran.
authors.forename: Noor Mohammad
authors.initials: NM
authors.lastname: Danesh
authors.affiliation: Academic Center for Education, Culture and Research (ACECR), Mashhad Branch, Mashhad, Iran; Department of Chemistry, Ferdowsi University of Mashhad, Mashhad, Iran.
authors.forename: Parirokh
authors.initials: P
authors.lastname: Lavaee
authors.affiliation: Cardiovascular Research Center, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ahmad Sarreshtehdar
authors.initials: AS
authors.lastname: Emrani
authors.affiliation: Department of Infectious Disease, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Koroush Yousefi
authors.initials: KY
authors.lastname: Hassanabad
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
authors.affiliation: Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: abnouskh@mums.ac.ir.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000737:chemistry* / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D016376:Oligonucleotides, Antisense; D006046:Gold; D003630:Daunorubicin
keywords: Antisense; Daunorubicin; Gold nanoparticles; Leukemia; Polyvalent aptamers; Targeted delivery