Self-assembly, DNA Complexation, and pH Response of Amphiphilic Dendrimers for Gene Transfection

Degradable Dual pH‐ and Temperature‐Responsive Photoluminescent Dendrimers

“…[12] Therefore, stimuliresponsive dendrimers offer a unique platform for many applications, [6,13] particularly biomedical engineering in developing intelligent devices that are able to sense biosignals or microenvironments, [14] such as tumor-sensitive contrast agents, [9,15] tumor-targeted drug release carriers, [16,17] and gene delivery carriers. [18] Dual responses to both temperature and pH offer two parameters for manipulating nanocarriers so as to achieve better targeting and efficacy in complicated microenvironments [19] or for other functions such as triggered release. [4,20,21] Current pH-or temperature-sensitive dendrimers are generally made from PAMAM-based dendrimers decorated with appropriate responsive moieties [7,11,22] as used in linear polymers, which include acid-sensitive polyacids [16,23] and polybases, [24,25] temperature-responsive alkylamides [21,26] and oligoethylene glycols, [27] or both if responses to both stimuli are required.…”

siRNA transfection by dendritic core–shell nanocarriers

“…[42, 66-67, 114, 116, 118, 131-133] Since these complexes carry extra positive charge on their surfaces they facilitate binding to cellular anionic proteins (glycoproteins, proteoglycans, and glycerolphosphates) and mediate the cellular entry by non-specific endocytosis as illustrated in Figure 9. [29,61,127,134] Furthermore, these particles, known as lipoplexes or polyplexes can protect the condensed genetic material to overcome biological obstacles, including undesired interactions with blood components associated with systemic delivery. [116,118,[135][136][137][138][139] Figure 9.…”

“…[165] Since these complexes carry a positive charge on their surfaces, they easily absorb the negatively charged cell surface and mediate the cellular entry by non-specific endocytosis. [29,61,127,134] Furthermore, these polycations, so-called "proton sponge" polymers, are able to induce membrane destabilization at acidic pH which is based on the fact that polyamines contain a large number of secondary amines and exhibit pKa values between physiological pH (7) and lysosomal pH (5-6). [166] During endocytic trafficking, these polymers get protonated and the accumulation of protons in the vesicle must be balanced by an influx of counter ions followed by osmotic swelling and finally rupture of the endosome which releases the polyplexes into the cytosol.…”

“…Furthermore he could show that stringently synthesized and purified PAMAM was 100-fold less active than partially degraded (= hyperbranched) PAMAM. [134,187] A comparison of the resulting DNA complexes formed by each polymer, whether perfect or hyperbranched, showed that both forms compact DNA structures of nearly the same size, which lead to the conclusion that the key for optimal transfection activity correlates to the polymer flexibility. [120] Hyperbranched polymers are highly branched molecules composed of dendritic (D), linear (L), and terminal units (T) that represent a compromise between the perfect structures of dendrimers and the partially degraded architectures.…”

“…[134,187] A comparison of the resulting DNA complexes formed by each polymer shows that both form compact DNA polyplexes of nearly the same size.…”