Low‐generation asymmetric dendrimers exhibit minimal toxicity and effectively complex DNA

Abstract

Conventional dendrimers are spherical symmetrically branched polymers ending with active surface functional groups. Polyamidoamine (PAMAM) dendrimers have been widely studied as gene delivery vectors and have proven effective at delivering DNA to cells in vitro. However, higher generation (G4-G8) PAMAM dendrimers exhibit toxicity due to their high cationic charge density and this has limited their application in vitro and in vivo. Another limitation arises when attempts are made to functionalize spherical dendrimers as targeting moieties cannot be sitespecifically attached. Therefore, we propose that lower generation asymmetric dendrimers, which are likely devoid of toxicity and to which site-specific attachment of targeting ligands can be achieved, would be a viable alternative to currently-available dendrimers. We synthesized and characterized a series of peptide-based asymmetric dendrimers and compared their toxicity profile and ability to condense DNA to spherical PAMAM G1 dendrimers. We show that asymmetric dendrimers are minimally toxic and condense DNA into stable toroids which have been reported necessary for efficient cell transfection. This paves the way for these systems to be conjugated with targeting ligands for gene delivery in vitro and in vivo. Shah et. al 3

Particle size- and number-dependent delivery to cells by layered double hydroxide nanoparticles

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A review on comparative study of PPI and PAMAM dendrimers

“…In drug delivery system, PAMAM and PPI dendrimers have played an important role in the field of nanomedicine (Kumari et al 2014;Myers et al 2001). Lower generations of PPI dendrimers like 0.0, 1.0 and 2.0G have open structure and showed high polarity range (Shah et al 2011;Winnicka et al 2009). In case of PAMAM dendrimers, many large number of internal pockets are available (Alamry et al 2015;Aldosari 2011).…”

Generation Dependent Safety and Efficacy of Folic Acid Conjugated Dendrimer Based Anticancer Drug Formulations

“…Jain and coworkers have examined and reported the influence of dendrimer generation on biocompatibility of dendrimer, wherein it was observed that dendrimers size is a predominant constraint related to its cytotoxicity (9,10). They recently examined the effect of necked dendrimer generation on drug delivery aptitude, and observed very high toxicities as evident by hemolysis, cytotoxicity and flow cytometry assays.…”