Hydrophobic Polyphenylalanine‐Grafted Hyperbranched Polyethylenimine and its in vitro Gene Transfection

Abstract

A series of amphiphilic multi-armed PPn copolymers were prepared by ROP of Phe-NCA with PEI-25k as a macroinitiator. The particle size of the PPn/DNA complexes was about 100 nm and the zeta potentials were below 20 mV. An MTT assay demonstrated that all the PPn copolymers had lower cytotoxicity compared to PEI-25k. In vitro gene transfection studies were also conducted in HeLa, 293 and CT 26 cells. The optimal quantity of hydrophobic phenylalanine segments in PP80 led to higher transfection efficiency in various cell lines based on this study. The results indicate that PP80 was the best candidate for gene delivery among these PPn copolymers.

Peptide-Based Polymer Therapeutics

“…Significant differences among treated and non-treated animals were observed, validating them as a possible therapy in glomerular diseases [145]. Poly(phenylalanine) has been also used for this purpose, either as part of an amphiphilic multi-armed copolymer using poly(ethyleneimine) (PEI) as macroinitiator achieving gene transfection in vitro [146] or co-polymerised with other molecules such as PLL (poly(lysine-co-phenylananine) observing translocation across the lipid bilayer and subsequent drug release into the cytoplasm [147].…”

Hybrid Block Copolymers Constituted by Peptides and Synthetic Polymers: An Overview of Synthetic Approaches, Supramolecular Behavior and Potential Applications

“…A related work consisted in the synthesis of amphiphilic multiarm star polymers based on a polyethylene imine (PEI) as a core molecule and polyphenylalanine (PPhe) arms of different degree of polymerization (i.e., 40-120), which were obtained by means of the corresponding NCA polymerization. The multiarm stars were subsequently used as gene carriers on studying the transfection efficiency with different cell lines [22].…”

“…For example, it is possible to have an accurate triggering and control over the different type of substance delivery (e.g., drugs, enzymes, genes) by taking into account the stimuli responsive behavior that some peptide blocks display in solution. Some of the recent advances in this field have also been commented in Section 2 [21][22][23]26,29,30,47,49,52,53,80].…”

PAMAM Dendrimer Conjugated with Cell‐penetrating Peptide‐derived Oligopeptides for Enhanced Cell Uptake and Gene Delivery

“…Extensive use of the polymer vector polyethylenimine (PEI 25 kDa) shows that it delivers genes with the highest efficiency due to the presence of many secondary and tertiary amine groups . Moreover, PEI 25 kDa binds DNA with high affinity and facilitates early endosomal escape owing to its “proton sponge effect.” Despite its ability to facilitate high levels of gene expression, the cytotoxicity associated with PEI 25 kDa is a matter of concern .…”