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Title
  • en A neutral lipid envelope-type nanoparticle composed of a pH-activated and vitamin E-scaffold lipid-like material as a platform for a gene carrier targeting renal cell carcinoma
Creator
Accessrights open access
Subject
  • Other en Cancer
  • Other en Gene delivery
  • Other en Renal carcinoma
  • Other en Angiogenesis
  • NDC 499
Description
  • Abstract en A renal cell carcinoma (RCC) is one of the refractory tumors, since it readily acquires resistance against chemotherapy. Thus, alternative therapeutic approaches such as obstructing the neovasculature are needed. We previously reported on the development of a plasmid DNA (pDNA)-encapsulating liposomal nanoparticle (LNP) as a hepatic gene delivery system that is applicable to systemic administration. The key molecular component is a SS-cleavable and pH-activated lipid-like material (ssPalm) that mounts dual sensing motifs (ternary amines and disulfide bonding) that are responsive to the intracellular environment. The main purpose of the present study was to expand its application to a tumor-targeting gene delivery systemin mice bearing tumors established from a RCC (OS-RC-2). When the modification of the surface of the particle is optimized for the polyethyleneglycol (PEG), stability in the blood circulation is improved, and consequently tumor-selective gene expression can be achieved. Furthermore, gene expression in the tumor was increased slightly when the hydrophobic scaffold of the ssPalm was replaced from the conventionally used myristic acid (ssPalmM) to alpha-tocopherol succinate (ssPalmE). Moreover, tumor growth was significantly suppressed when the completely CpG-free pDNA encoding the solute form of VEGFR (fms-like tyrosine kinase-1: sFlt-1) was used, especially when it was delivered by the LNP formed with ssPalmE(LNPssPalmE). Thus, the PEG-modified LNPssPalmE is a promising gene carrier for the cancer gene therapy of RCC. (C) 2014 Elsevier B.V. All rights reserved.
Publisher en Elsevier
Date
    Issued2015-02-28
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/58129
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.jconrel.2014.12.029
  • PMID 25543000
Journal
    • PISSN 0168-3659
      • en Journal of controlled release
      • Volume Number200 Page Start97 Page End105
File
Oaidate 2023-07-26