Synergistic effect of amino acids modified on dendrimer surface in gene delivery

Polyamidoamine (PAMAM) dendrimers modified with short oligopeptides for early endosomal escape and enhanced gene delivery

“…As previously proposed with the cellular uptake results, higher cellular internalization of the PAMAM G4 derivatives probably led to higher transfection efficiency and negligible toxicity than that of the PAMAM G4. This result is consistent with a previous report showing that the combination of hydrophobic and hydrophilic groups improves transfection efficiency (Wang et al, 2014;Zhi et al, 2010). Therefore, the combination of arginine, histidine, and phenylalanine to achieve similar levels of gene expression can be a novel strategy for the production of safe and effective gene carriers.…”

Synthesis and NMR characterization of dendrimers based on 2, 2-bis-(hydroxymethyl)-propanoic acid (bis-HMPA) containing peripheral amino acid residues for gene transfection

“…To decrease toxicity and improve biodegradability of PAMAM, research efforts focused on their chemical modification such as acetylation, 20,21 PEGylation, 22 introduction of pyrrolidone, 23 carbohydrate, 24,25 amino acid [26][27][28] and peptide 29 residues. A different approach to reduce cytotoxicity in polycationic vectors was to introduce hydrolyzable linkages, as the ester groups, as applied both to PAMAM 30 itself and to non dendrimeric vectors such as poly(β-amino esters).…”

“…A different approach to reduce cytotoxicity in polycationic vectors was to introduce hydrolyzable linkages, as the ester groups, as applied both to PAMAM 30 itself and to non dendrimeric vectors such as poly(β-amino esters). [31][32][33] Moreover, dendrimers containing amino acid residues 26,[34][35][36] have aroused great interest since the diversity of amino acid moiety can meet the recognized requirement for modulating the buffer capacity of the vector and facilitate its escape from endosomal acidic compartments through membrane disruption of endosomes. 10 On this ground, with the aim of preparing hydrolyzable dendrimer structures which were, at the same time, adequately protonated but also well tolerated by the cells and which could harmonize transfection capacity with a low level of toxicity, we report in this work versatile chemical protocols for the synthesis of a library of 15 dendrimers of fourth, fifth and sixth generation derived from 2,2-bis(hydroxymethyl)propanoic acid (bis-HMPA), a monomer of the AB 2 type used to prepare a variety of dendritic architectures.…”

Reduction-responsive cross-linked stearyl peptide for effective delivery of plasmid DNA

“…Next, 100 μL of C-SHR-3/ pGL3 in 5% glucose solution (212 μg C-SHR-3 combined with 20 μg pGL3, N/P ratio 10) was injected into the tumor at a pGL3 dose of 1 mg/kg every day for 3 days. 21 A group treated with SHR/pGL3 complexes in 5% glucose solution was used as the control. Forty-eight hours after the final injection, d-luciferin potassium salt (200 μL, 150 mg/kg) was injected intraperitoneally into the mice which were anesthetized by pentobarbital sodium (70 μL, 0.02 mg/mL).…”