Correction: Fusogenic peptide modification to enhance gene delivery by peptide-DNA nano-coassemblies.

Correction for 'Fusogenic peptide modification to enhance gene delivery by peptide-DNA nano-coassemblies' by Ruilu Feng et al., Biomater. Sci., 2022, 10, 5116-5120, https://doi.org/10.1039/D2BM00705C.

Fusogenic peptide modification to enhance gene delivery by peptide-DNA nano-coassemblies.

Endosomal escape is a major obstacle for non-viral nucleic acids delivery. Here, we attached by click reaction a fusogenic peptide (L17E) onto peptide self-assembled disks (∼17 nm), which mimicked the functional subunits of the virus capsid. These peptide disks then spontaneously co-assembled with DNA to form patterned nanostructures (∼100 nm) as viral mimics. This modification did not affect the cellular uptake but enhanced endosomal escape and led to improved transfection in cell culture.

mRNA Delivery and Storage by Co-Assembling Nanostructures with Designer Oligopeptides.

Broadening the applicable tools for mRNA delivery provides more flexibility in research and those proven effective and safe can potentially be translated for clinical use. We report here a 27-amino acid peptide sequence mimicking the viral capsid protein, termed pepMAX, capable of co-assembling with mRNA into 100-150 nm nanostructures for efficient transfection of multiple cell lines. The mRNA loading and N/P ratio have been systematically optimized for each cell line. In HeLa, HEK293, and SKNMC, the transfection attained (>80%) is comparable with that of commercially available vectors Lipofectamine MessengerMAXTM (LipoMMAX). Confocal microscopy reveals that pepMAX efficiently delivers mRNA into the cytosol and induces efficient protein production. The pepMAX/mRNA co-assemblies retain their transfection efficiency after storage up to one week at room temperature in lyophilized form.

Altered Peptide Self-Assembly and Co-Assembly with DNA by Modification of Aromatic Residues.

Aromatic residues are widely used as building blocks for driving self-assemblies in natural and designer biomaterials. The noncovalent interactions involving aromatic rings determine proteins' structure and biofunction. Here, we studied the effects of changes in the proximity of the aromatic rings in a self-assembling peptide for modulating interactions involving the aromatic residues. By changing the distance between the aromatic ring and peptide backbone and replacing the side chain with a sulfur atom, we altered the nanostructures and gene transfection efficiency of peptide-DNA co-assemblies. This study demonstrates the significance of subtle alterations in aromatic interactions and facilitates deeper understanding of the aromatic-involving interactions.

Synthetic Approaches for Nucleic Acid Delivery: Choosing the Right Carriers.

The discovery of the genetic roots of various human diseases has motivated the exploration of different exogenous nucleic acids as therapeutic agents to treat these genetic disorders (inherited or acquired). However, the physicochemical properties of nucleic acids render them liable to degradation and also restrict their cellular entrance and gene translation/inhibition at the correct cellular location. Therefore, gene condensation/protection and guided intracellular trafficking are necessary for exogenous nucleic acids to function inside cells. Diversified cationic formulation materials, including natural and synthetic lipids, polymers, and proteins/peptides, have been developed to facilitate the intracellular transportation of exogenous nucleic acids. The chemical properties of different formulation materials determine their special features for nucleic acid delivery, so understanding the property-function correlation of the formulation materials will inspire the development of next-generation gene delivery carriers. Therefore, in this review, we focus on the chemical properties of different types of formulation materials and discuss how these formulation materials function as protectors and cellular pathfinders for nucleic acids, bringing them to their destination by overcoming different cellular barriers.

A facile methodology using quantum dot multiplex labels for tracking co-transfection.

Advances in the field of genome engineering demand the development of efficient non-viral transfection agents capable of delivering multiple distinct nucleic acids efficiently to cells (co-transfection). However, current delivery methods result in lower co-transfection efficiency than single plasmid transfections, and the efficiency decreases further with increasing numbers of plasmids. The development of a high-throughput methodology is required for the validation of co-transfection platforms to facilitate independent tracking of not only the multiple DNA plasmids during transfection but also the localisation of transfection agents. This is pivotal to determine the bottlenecks in achieving high transfection efficiencies at various stages of the cell internalisation and plasmid expression process. Herein we demonstrate that this can be achieved using a facile methodology in which quantum dots (QDs) are used to label two different plasmid DNA assemblies that are delivered to cells simultaneously using a dendronised polymer system. Multispectral confocal imaging can be used to separate signals from each polyplex as well as the expressed fluorescent reporter proteins to determine whether co-transfection difficulties result from poor internalisation or the inability of DNA to escape from polyplexes. The results demonstrate the utility of this facile approach to label polyplexes without interfering with gene expression, and enable high-throughput screening of transfection reagents for achieving optimal co-transfection.

Novel Metal Polyphenol Framework for MR Imaging-Guided Photothermal Therapy.

Phothermal therapy has received increasing attention in recent years as a potentially effective way to treat cancer. In pursuit of a more biocompatible photothermal agent, we utilize biosafe materials including ellagic acid (EA), polyvinylpyrrolidone (PVP), and iron element as building blocks, and we successfully fabricate a homogeneous nanosized Fe-EA framework for the first time by a facile method. As expected, the novel nanoagent exhibits no obvious cytotoxicity and good hemocompatibility in vitro and in vivo. The microenvironment responsiveness to both pH and hydrogen peroxide makes the NPs biodegradable in tumor tissues, and the framework should be easily cleared by the body. Photothermal potentials of the nanoparticles are demonstrated with relevant features of strong NIR light absorption, moderately effective photothermal conversion efficiency, and good photothermal stability. The in vivo photothermal therapy also achieved effective tumor ablation with no apparent toxicity. On the other hand, it also exhibits T2 MR imaging ability originated from ferric ions. Our work highlights the promise of the Fe-EA framework for imaging-guided photothermal therapy.

Bimetallic Zeolitic Imidazolate Framework as an Intrinsic Two-Photon Fluorescence and pH-Responsive MR Imaging Agent.

Zeolitic imidazolate framework-8 (ZIF-8) has received wide attention in recent years as a potential drug vehicle for the treatment of cancer due to its acid-responsiveness and moderate biocompatibility. However, its congenital deficiency of intrinsic imaging capability limits its wider applications; therefore, a postsynthetic exchange approach was utilized to introduce paramagnetic manganese(II) ions into the ZIF-8 matrix. As a result, bimetallic zeolitic imidazolate frameworks (Mn-Zn-ZIF) were thus fabricated and exhibited pH-responsive T1-weighted magnetic resonance imaging (MRI) contrast effect. Remarkably, we also found its own fluorescence derived from 2-methylimidazole, which is the first report of the intrinsic two-photon fluorescence imaging of ZIFs to our knowledge. Mn-Zn-ZIF still preserves the original properties of ZIF-8 of high surface areas, microporosity, and acid sensitivity. After further PEGylation of Mn-Zn-ZIF, the nanoparticles showed no obvious toxicity and its MRI contrast effect has also been enhanced. Our work highlights the promise of modified zeolitic imidazolate frameworks as potential cancer theranostic platforms.

Rapid Adsorption Enables Interface Engineering of PdMnCo Alloy/Nitrogen-Doped Carbon as Highly Efficient Electrocatalysts for Hydrogen Evolution Reaction.

The catalytic performance of Pd-based catalysts has long been hindered by surface contamination, particle agglomeration, and lack of rational structural design. Here we report a simple adsorption method for rapid synthesis (∼90 s) of structure-optimized Pd alloy supported on nitrogen-doped carbon without the use of surfactants or extra reducing agents. The material shows much lower overpotential than 30 wt % Pd/C and 40 wt % Pt/C catalysts while exhibiting excellent durability (80 h). Moreover, unveiled by the density functional theory (DFT) calculation results, the underlying reason for the outstanding performance is that the PdMnCo alloy/pyridinic nitrogen-doped carbon interfaces weaken the hydrogen-adsorption energy on the catalyst and thus optimize the Gibbs free energy of the intermediate state (ΔGH*), leading to a remarkable electrocatalytic activity. This work also opens up an avenue for quick synthesis of a highly efficient structure-optimized Pd-based catalyst.