Application of new lysine-based peptide dendrimers D3K2 and D3G2 for gene delivery: Specific cytotoxicity to cancer cells and transfection in vitro

Michal Gorzkiewicz, Malgorzata Konopka, Anna Janaszewska, Irina I. Tarasenko, Nadezhda N. Sheveleva, Arkadiusz Gajek, Igor M. Neelov, Barbara Klajnert-Maculewicz

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

In order to enhance intracellular uptake and accumulation of therapeutic nucleic acids for improved gene therapy methods, numerous delivery vectors have been elaborated. Based on their origin, gene carriers are generally classified as viral or non-viral vectors. Due to their significantly reduced immunogenicity and highly optimized methods of synthesis, nanoparticles (especially those imitating natural biomolecules) constitute a promising alternative for virus-based delivery devices. Thus, we set out to develop innovative peptide dendrimers for clinical application as transfection agents and gene carriers. In the present work we describe the synthesis of two novel lysine-based dendritic macromolecules (D3K2 and D3G2) and their initial characterization for cytotoxicity/genotoxicity and transfection potential in two human cell line models: cervix adenocarcinoma (HeLa) and microvascular endothelial (HMEC-1). This approach allowed us to identify more cationic D3K2 as potent delivery agent, being able to increase intracellular accumulation of large nucleic acid molecules such as plasmids. Moreover, the dendrimers exhibited specific cytotoxicity towards cancer cell line without showing significant toxic effects on normal cells. These observations are promising prognosis for future clinical application of this type of nanoparticles.

Original languageEnglish
Article number103504
Pages (from-to)103504
Number of pages11
JournalBioorganic Chemistry
Volume95
DOIs
StatePublished - Jan 2020

Scopus subject areas

  • Drug Discovery
  • Molecular Biology
  • Biochemistry
  • Organic Chemistry

Keywords

  • VIRAL VECTORS
  • POLYAMIDOAMINE DENDRIMERS
  • CATIONIC POLYMERS
  • THERAPY
  • ASSAY
  • DNA
  • BIODISTRIBUTION
  • POLY(L-LYSINES)
  • MICROBICIDES
  • MECHANISMS

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