Aliphatic Quaternary Ammonium Functionalized Nanogels for Gene Delivery

Abstract

Gene therapy is a promising treatment for hereditary diseases, as well as acquired genetic diseases, including cancer. Facing the complicated physiological and pathological environment in vivo, developing efficient non-viral gene vectors is needed for their clinical application. Here, poly(N-isopropylacrylamide) (p(NIPAM)) nanogels are presented with either protonatable tertiary amine groups or permanently charged quaternized ammonium groups to achieve DNA complexation ability. In addition, a quaternary ammonium-functionalized nanogel was further provided with an aliphatic moiety using 1-bromododecane to add a membrane-interacting structure to ultimately facilitate intracellular release of the genetic material. The ability of the tertiary amine-, quaternized ammonium-, and aliphatic quaternized ammonium-functionalized p(NIPAM) nanogels (i.e., NGs, NGs-MI, and NGs-BDD, respectively) to mediate gene transfection was evaluated by fluorescence microscopy and flow cytometry. It is observed that NGs-BDD/pDNA complexes exhibit efficient gene loading, gene protection ability, and intracellular uptake similar to that of NGs-MI/pDNA complexes. However, only the NGs-BDD/pDNA complexes show a notable gene transfer efficiency, which can be ascribed to their ability to mediate DNA escape from endosomes. We conclude that NGs-BDD displays a cationic lipid-like behavior that facilitates endosomal escape by perturbing the endosomal/lysosomal membrane. These findings demonstrate that the presence of aliphatic chains within the nanogel is instrumental in accomplishing gene delivery, which provides a rationale for the further development of nanogel-based gene delivery systems.

Thermo‐sensitive ionic hydrogels synthesis via post quaternization cross‐linking: A highly efficient reusable catalytic thermo‐responsive nanoreactors

“…It seems that as the length of the quaternized alkyl chains was raised, there was a slight reduction in the VPTT of the quaternized hydrogels. Furthermore, the change in the chain length led to a wider phase transition temperature range 35 . In addition, Zhou et al synthesized PIL cross‐linked PNIPAM hydrogels via simultaneous quaternized cross‐linking reaction and observed broad transition behavior between 35°C and 50 ° C, which was very different from the sharp transition behavior of linear PINIPAM polymers (LCST ~32 ° C) 36 …”

“…Furthermore, the change in the chain length led to a wider phase transition temperature range. 35 In addition, Zhou et al synthesized PIL crosslinked PNIPAM hydrogels via simultaneous quaternized cross-linking reaction and observed broad transition behavior between 35 C and 50 C, which was very different from the sharp transition behavior of linear PINIPAM polymers (LCST $32 C). 36 Figure S6 shows a typical XRD pattern of Ag NPs, with diffraction peaks at 2θ values of 38.2 , 44.4 , 64.5 , and 77.6 corresponding to the (111), ( 200), (220), and (311) planes of face-centered cubic Ag (JCPDS 04-0783), [37] and confirms the formation of zero-valent silver NPs inside the polymer matrix.…”

One-pot synthesis of quaternary pyridinium salts of lupane triterpenoids and their antimicrobial properties

“…This property is typical for amphiphilic molecules or fragments of molecules, which have a high affinity for the lipid bilayer of plasma and intracellular membranes. 6,7 Natural triterpenoids are successfully used as amphiphilic molecules, since they have low toxicity and a high affinity for phospholipid membranes. 8 The major disadvantage that hinders the use of all known terpenoid analogs as drugs is low bioavailability associated with poor solubility in biological fluids, which limits their effective interaction with biological targets.…”

“…Yield of products in the reaction of lupane triterpenoids with PyÁ HBrÁBr 2 in the medium of pyridines (mole ratio[1][2][3][4][5][6][7][8][9] : [pyridine] : [brominating agent] = 1 : 225 : 2.5) and theoretical values of their lipophilicity log P…”