Materials Science and Engineering: C 2016-04-01

Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers.

Maryam Hashemi, Seyed Meghdad Tabatabai, Hamideh Parhiz, Soroush Milanizadeh, Sara Amel Farzad, Khalil Abnous, Mohammad Ramezani

Index: Mater. Sci. Eng. C. Mater. Biol. Appl. 61 , 791-800, (2016)

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Abstract

Poly-(amidoamine) (PAMAM) and poly-(propylenimine) (PPI) are the two most widely investigated dendrimers for drug and gene delivery. In order to enhance DNA transfection activity of these dendrimers, generation 3 and 4 PAMAM and generation 4 and 5 PPI were modified by partial substitution of surface primary amines with histidine, pyridine, and piperazine, which have buffering capacity properties. It was shown that higher dendrimer generations and higher grafting percentages (30% and 50% of primary amines) were associated with higher transfection activity. Pyridine was the most effective substituent for PPI, while piperazine-modified PAMAM dendrimers showed the best transfection efficiency among PAMAM-based vectors in murine neuroblastoma (Neuro-2a) cells. None of the modified carriers showed remarkable cytotoxicity in vitro. Pretreatment of cells with bafilomycin A indicated that endosomal buffering capacity is the main mechanism of endosomal escape. In conclusion, PAMAM and PPI may exhibit different gene delivery efficiency and cytotoxicity profiles with the same chemical modifications. These modified dendrimers could be considered as efficient and safe gene carriers in neuroblastoma cells in vitro. Copyright © 2016 Elsevier B.V. All rights reserved.

Related Compounds

  • 1-(3-Dimethylamino...
  • Histidine hydrochl...
  • 2-Piperazinecarbox...
  • 2-(Pyridin-3-yl)ac...

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