Smart AS1411-aptamer conjugated pegylated PAMAM dendrimer for the superior delivery of camptothecin to colon adenocarcinoma in vitro and in vivo.

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  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
    • Subject Terms:
      Adenocarcinoma/*drug therapy ; Camptothecin/*administration & dosage ; Camptothecin/*chemistry ; Colon/*drug effects ; Colonic Neoplasms/*drug therapy ; Dendrimers/*chemistry ; Oligodeoxyribonucleotides/*chemistry; Adenocarcinoma/metabolism ; Animals ; Aptamers, Nucleotide ; CHO Cells ; Cell Line, Tumor ; Colon/metabolism ; Colonic Neoplasms/metabolism ; Cricetulus ; Drug Carriers/chemistry ; Drug Delivery Systems/methods ; HT29 Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Nanoparticles/chemistry ; Phosphoproteins/metabolism ; RNA-Binding Proteins/metabolism ; Nucleolin
    • 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.
      (Copyright © 2017 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: AS1411; Camptothecin; Dendrimer; PAMAM; Targeted drug delivery
    • Accession Number:
      0 (AGRO 100)
      0 (Aptamers, Nucleotide)
      0 (Dendrimers)
      0 (Drug Carriers)
      0 (Oligodeoxyribonucleotides)
      0 (PAMAM Starburst)
      0 (Phosphoproteins)
      0 (RNA-Binding Proteins)
      XT3Z54Z28A (Camptothecin)
    • Publication Date:
      Date Created: 20170128 Date Completed: 20170616 Latest Revision: 20231213
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.ijpharm.2017.01.044
    • Accession Number:
      28126548