Design and synthesis of biologically active cationic amphiphiles built on the calix[4]arene scaffold

Non-Viral in Vitro Gene Delivery: It is Now Time to Set the Bar!

“…Some authors have indeed reported that the transfection efficiency of bPEI in vitro increased with increasing the M W of the CP (in the range from ≈1.8 to ≈70 kDa) [62,114], while others have highlighted that the lower the M W of the branched polymer (≈12 kDa), the greater the effectiveness [115]. Further, we and some others have pointed out the different pDNA complexation ability of lPEI and bPEI and have found that, irrespective of the M W of the CP taken into account, lPEIs complex best at N/P 5, while bPEIs at N/P 3 [57,62,64,116,117]. This different behavior may be ascribed to the different structures of the PEI isomers: of note, lPEI possesses only secondary amines, while bPEI has primary, secondary, and tertiary amines depending on the polymerization degree [118].…”

“…Because they are relatively safe, display easily tunable physico-chemical properties, can be produced in large quantities with high reproducibility and affordable costs, and show unlimited ferrying capacity [53][54][55], non-viral vectors are nowadays at the forefront of gene delivery [1]. The two major approaches to non-viral gene delivery involve the combination of NAs with transfection molecules, that is, cationic lipids (CLs; e.g., DOTAP, DOTMA) [56][57][58][59][60][61] in different forms, and cationic polymers (CPs; e.g., poly-L-lysines, polyethyleneimines (PEIs), poly(amidoamine)s, chitosans) [62][63][64][65][66][67]. The beauty of this approach lies in its simplicity, yet in its effectiveness.…”

“…Overall, the good gene delivery performances of PEIs, together with moderate cytotoxicity they exert, disclose this class of CPs as gold standard transfectants. As such, they have been largely used as benchmark transfectants in most of the in vitro studies [57,112]. As a rule of thumb, according to ISO norms, reference materials are those whose properties are sufficiently homogeneous and well established to be used for assigning values to other materials [119,120], which in practice means to other transfectants being developed.…”

“…Yet, the way polyplexes are added to cells may also dramatically affect the transfection efficiency. By and large, the delivery of complexes to cells is obtained through the addition of the transfection suspension to the cells cultured in the culture medium [62,96], or the culture vessel in which the cells were plated is emptied, polyplexes are first pre-diluted in the culture medium and then added to the cells [57,64]. As a general observation, lPEI-polyplexes prepared in 10 mM Hepes have smaller D H and are more effective when directly added to the transfection well, while bigger particles (e.g., those prepared in 150 mM NaCl) benefit from the pre-dilution step in cell culture medium before they are incubated with cells (Figure 6b).…”

Impact of Tetracationic Calix[4]arene Conformation—from Conic Structure to Expanded Bolaform—on Their Antibacterial and Antimycobacterial Activities

“…The last thirty years have witnessed growing interest in calixarene chemistry, due to their excellent organizational behavior involving various chemical functions that permit highly diverse fields of application to be addressed . Even though they remain somewhat confidential, the applications of calixarenes in biology are constantly increasing in very different fields such as protein–surface recognition, cell transfection, and DNA condensation…, as anti‐infectives, or as anti‐infectives including intrinsically active species and prodrugs, but also in the form of recently reported amphiphilic species combining both transfective and antibacterial properties …”