Revealing the impact of modified modules flexibility on gemcitabine prodrug nanoassemblies for effective cancer therapy.

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  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0043125 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-7103 (Electronic) Linking ISSN: 00219797 NLM ISO Abbreviation: J Colloid Interface Sci Subsets: MEDLINE
    • Publication Information:
      Publication: Orlando, FL : Academic Press
      Original Publication: New York.
    • Subject Terms:
      Gemcitabine* ; Deoxycytidine*/analogs & derivatives ; Deoxycytidine*/chemistry ; Deoxycytidine*/pharmacology ; Prodrugs*/chemistry ; Prodrugs*/pharmacology ; Drug Liberation*; Humans ; Animals ; Mice ; Drug Screening Assays, Antitumor ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Survival/drug effects ; Nanoparticles/chemistry ; Cell Proliferation/drug effects ; Particle Size ; Antimetabolites, Antineoplastic/chemistry ; Antimetabolites, Antineoplastic/pharmacology ; Cell Line, Tumor ; Molecular Structure ; Surface Properties ; Mice, Inbred BALB C
    • Abstract:
      Prodrug nanoassemblies combine the advantages of prodrug strategies and nanotechnology have been widely utilized for delivering antitumor drugs. These prodrugs typically comprise active drug modules, response modules, and modification modules. Among them, the modification modules play a critical factor in improving the self-assembly ability of the parent drug. However, the impact of the specific structure of the modification modules on prodrug self-assembly remains elusive. In this study, two gemcitabine (GEM) prodrugs are developed using 2-octyl-1-dodecanol (OD) as flexible modification modules and cholesterol (CLS) as rigid modification modules. Interestingly, the differences in the chemical structure of modification modules significantly affect the assembly performance, drug release, cytotoxicity, tumor accumulation, and antitumor efficacy of prodrug nanoassemblies. It is noteworthy that the prodrug nanoassemblies constructed with flexible modifying chains (OD) exhibit improved stability, faster drug release, and enhanced antitumor effects. Our findings elucidate the significant impact of modification modules on the construction of prodrug nanoassemblies.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: Antitumor therapy; Flexibility; Gemcitabine; Modification modules; Prodrug nanoassemblies
    • Accession Number:
      0 (Gemcitabine)
      0W860991D6 (Deoxycytidine)
      0 (Prodrugs)
      0 (Antineoplastic Agents)
      0 (Antimetabolites, Antineoplastic)
    • Publication Date:
      Date Created: 20240811 Date Completed: 20241008 Latest Revision: 20241008
    • Publication Date:
      20241008
    • Accession Number:
      10.1016/j.jcis.2024.08.026
    • Accession Number:
      39128288