title: Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.
abstract: In the current study camptothecin-loaded pegylated PAMAM dendrimer were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against colorectal cancer cells which over expresses nucleolin receptors. The morphological properties and size dispersity of the prepared nanoparticles were evaluated using transmission electron microscope (TEM) and DLS. The drug-loading content and encapsulation efficiency were obtained 8.1% and 93.67% respectively. The in vitro release of camptothecin from the formulation was provided the sustained release of encapsulated camptothecin during 4days. Comparative in vitro cytotoxicity experiments demonstrated that the targeted camptothecin loaded-pegylated dendrimers had higher antiproliferation activity, towards nucleolin-positive HT29 and C26 colorectal cancer cells than nucleolin-negative CHO cell line. Fluorscence microscopy and flow cytometry also confirmed the enhanced cellular uptake of AS1411 targeted pegylated-dendrimer. In vivo study in C26 tumor-bearing BALB/C mice revealed that the AS1411-functionalized camptothecin loaded pegylated dendrimers improved antitumor activity and survival rate of the encapsulated camptothecin. Conjugation of AS1411 aptamer to the camptothecin loaded-pegylated dendrimer surface provides site-specific delivery of camptothecin, inhibit C26 tumor growth in vivo and significantly decrease systemic toxicity. These results suggested that the new nucleolin-targeted pegylated PAMAM dendrimer as a delivery system for camptothecin have the potential for the treatment of nucleolin-overexpressed colorectal cancer.
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mona
authors.initials: M
authors.lastname: Alibolandi
authors.affiliation: Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Taghdisi
authors.affiliation: Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Pouria
authors.initials: P
authors.lastname: Ramezani
authors.affiliation: Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fazileh
authors.initials: F
authors.lastname: Hosseini Shamili
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Sara Amel
authors.initials: SA
authors.lastname: Farzad
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: abnouskh@mums.ac.ir.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ramezanim@mums.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ramezani
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D052157:Aptamers, Nucleotide; D016466:CHO Cells; D002166:Camptothecin / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003412:Cricetulus; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D010750:Phosphoproteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D000097796:Nucleolin
chemical_list: D052157:Aptamers, Nucleotide; D002166:Camptothecin; D050091:Dendrimers; D004337:Drug Carriers; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C513936:AGRO 100; C104700:PAMAM Starburst
keywords: AS1411; Camptothecin; Dendrimer; PAMAM; Targeted drug delivery