Festphasen‐basierte Synthese sequenzdefinierter T‐, i‐ und U‐Form‐Polymere für den pDNA‐ und siRNA‐Transfer

Abstract

wurde bereits für den DNA-Transfer beschrieben. [2,3] Hartmann, Bçrner und Kollegen verçffentlichten eine Syntheseroute zu Polyamidoaminen, die auf der abwechselnden Kupplung von Bernsteinsäureanhydrid und Diamino-Nmethyldipropylamin bzw. geschützter Spermin-Derivate beruht.[4] Um die Vorteile der Peptidsynthese mit der breiten chemischen Diversität synthetischer Polymere zu kombinieren, entwickelten wir künstliche Fmoc/Boc-geschützte Aminosäuren, die definierte Diaminoethan-Einheiten enthalten.[5] Dieses Motiv verfügt als "Protonenschwamm" über die Fähigkeit zur Endosomen-Destabilisierung, welche für die Transfektionseffizienz von Polyethylenimin (PEI) [6, 7] und weiteren kationischen Polymeren entscheidend ist.[8] Die biologische Aktivität ist dadurch viel hçher als bei Diaminopropan-Einheiten, die bereits bei neutralem pH vollständig protoniert sind.

Tumoral gene silencing by receptor-targeted combinatorial siRNA polyplexes

“…To examine the effect of PEG shielding on the surface charge of TCPs, zeta potentials of siRNA polyplexes at N/P 16 were measured (Table 1). For TCP1, TCP2 and TCP4, the zeta potential values were reduced from approximately ≥ +20 mV [30] to values around + 8-9 mV. It is interesting to see that TCP3, comprising the same oligomers by a different activation scheme, displays a highly positive zeta potential of +24 mV.…”

“…3-arm Stp oligomers 386 and 689, was chosen for their strong siRNA binding ability, which provide a highly stable cationic core to compact siRNA [30,33,40,46]. Moreover, PEG-folate-conjugated Sph oligomers (4-arm) 709 and (2-arm) 717, were used for folate receptor (FR) targeting and surface shielding [43].…”

“…The artificial oligoamino acids, such as succinoyl-tetraethylene pentamine (Stp) and succinoyl-pentaethylene hexamine (Sph) [29], in combination with natural α-amino acids, were applied in solid-phase assisted synthesis to generate sequence-defined cationic oligomers [30]. These oligomers provide excellent nucleic acid binding ability, endosomal buffering capacity, and site-specific positioning of multiple functionalities.…”

Recent progress in development of siRNA delivery vehicles for cancer therapy

“…Design of building components to maintain multimolecular structures is a key point to increase delivery efficacy. Various features in building components, e.g., chemical structures and length of building components (cationic moieties, nonionic/hydrophilic moieties, and hydrocarbon tail of lipid) contribute to vehicles stability [17,[104][105][106].…”

Dual‐Function CXCR4 Antagonist Polyplexes To Deliver Gene Therapy and Inhibit Cancer Cell Invasion

“…Significant effort has been devoted to synthesizing polycations that have improved transfection activity and reduced toxicity. [1] Traditionally, polycations have been seen as pharmacologically inert components of delivery systems.…”