Modulating Lipid Nanoparticles with Histidinamide-Conjugated Cholesterol for Improved Intracellular Delivery of mRNA.

Recently, mRNA-based therapeutics, including vaccines, have gained significant attention in the field of gene therapy for treating various diseases. Among the various mRNA delivery vehicles, lipid nanoparticles (LNPs) have emerged as promising vehicles for packaging and delivering mRNA with low immunogenicity. However, while mRNA delivery has several advantages, the delivery efficiency and stability of LNPs remain challenging for mRNA therapy.

Second-Generation Polyamidoamine Dendrimer Conjugated with Oligopeptides Can Enhance Plasmid DNA Delivery In Vitro.

Poly(amidoamine) (PAMAM) dendrimers have attracted considerable attention in the field of gene therapy due to their flexibility in introducing different functional moieties and reduced toxicity at low generations. However, their transfection efficiency remains a limitation. Therefore, an essential approach for improving their transfection efficiency as gene carriers involves modifying the structure of PAMAM by conjugating functional groups around their surface.

Crystal Structures of Plk1 Polo-Box Domain Bound to the Human Papillomavirus Minor Capsid Protein L2-Derived Peptide.

Human papillomaviruses (HPVs) can increase the proliferation of infected cells during HPV-driven abnormalities, such as cervical cancer or benign warts. To date, more than 200 HPV genotypes have been identified, most of which are classified into three major genera: Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus. HPV genomes commonly encode two structural (L1 and L2) and seven functional (E1, E2, E4-E7, and E8) proteins.

Crystal structure of Bak bound to the BH3 domain of Bnip5, a noncanonical BH3 domain-containing protein.

The activation or inactivation of B-cell lymphoma-2 (Bcl-2) antagonist/killer (Bak) is critical for controlling mitochondrial outer membrane permeabilization-dependent apoptosis. Its pro-apoptotic activity is controlled by intermolecular interactions with the Bcl-2 homology 3 (BH3) domain, which is accommodated in the hydrophobic pocket of Bak. Bcl-2-interacting protein 5 (Bnip5) is a noncanonical BH3 domain-containing protein that interacts with Bak.

Coordination-driven robust antibacterial coatings using catechol-conjugated carboxymethyl chitosan.

To prevent bacterial contamination on solid surfaces, a simple yet efficient antibacterial coating was developed in a substrate-independent manner by using the catechol-conjugated carboxymethyl chitosan (CMC-DOPA). The CMC-DOPA was firstly synthesized via an aza-Michael reaction with methyl acrylate and the subsequent acyl substitution with dopamine. The coating strategy consists of spin-coating-assisted deposition of CMC-DOPA on polydopamine-coated substrates and coordination-driven crosslinks between catechol groups and Fe ions in sequence, producing the multilayered CMC-DOPA films.

Conjugation of Short Oligopeptides to a Second-Generation Polyamidoamine Dendrimer Shows Antibacterial Activity.

The growing evolution of bacterial resistance to antibiotics represents a global issue that not only impacts healthcare systems but also political and economic processes. This necessitates the development of novel antibacterial agents. Antimicrobial peptides have shown promise in this regard.

Nanoemulsion Composed of α-Tocopherol Succinate and Dequalinium Shows Mitochondria-Targeting and Anticancer Effects.

Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic delivery are detailed in many nanoemulsion studies and show the tremendous potential of targeted delivery to inhibit cancer cell growth. Dequalinium (DQA) and α-tocopherol succinate (α-TOS) are good agents for targeting mitochondria.

Curcumin-Based Universal Grafting of Poly(OEGMA) Brushes and Their Antibacterial Applications.

Catechol and/or pyrogallol groups are recognized as crucial for the formation of polyphenol coatings on various substrates. Meanwhile, studies on polyphenolic molecules that do not contain such groups are relatively rare. The key molecule in turmeric-based universal (i.

Coordination-Driven Surface Zwitteration for Antibacterial and Antifog Applications.

The enhancement of surface wettability by hydrophilic polymer coatings has been of great interest because it has been used to address several technical challenges such as biofouling and surface fogging. Among the hydrophilic polymers, zwitterionic polymers have been extensively utilized to coat solid surfaces due to their excellent capability to bind water molecules, thereby forming dense hydration layers on the solid surfaces. For these zwitterionic polymers to function appropriately on the solid surfaces, techniques for fixing polymers onto the solid surface with high efficiency are required.

Enzyme-Responsive Amphiphilic Peptide Nanoparticles for Biocompatible and Efficient Drug Delivery.

Self-assembled peptide nanostructures recently have gained much attention as drug delivery systems. As biomolecules, peptides have enhanced biocompatibility and biodegradability compared to polymer-based carriers. We introduce a peptide nanoparticle system containing arginine, histidine, and an enzyme-responsive core of repeating GLFG oligopeptides.

Preparation and characterization of polyamidoamine dendrimers conjugated with cholesteryl-dipeptide as gene carriers in HeLa cells.

Improving the transfection efficiency of non-viral carriers by using cationic polymers is a useful approach to addressing several challenges in gene therapy, such as cellular uptake, endosomal escape, and toxicity. Among the various cationic polymers, polyamidoamine (PAMAM) dendrimers have been widely utilized because of the abundance of terminal functional groups, thereby enabling further functionalization and enhancing DNA condensation and internalization into cells. The combination of various functional groups is required for these PAMAM dendrimer derivatives to function appropriately for gene delivery.

Dual-Functional Dendrimer Micelles with Glycyrrhizic Acid for Anti-Inflammatory Therapy of Acute Lung Injury.

Dendrimer micelles with glycyrrhizic acid (GA) were developed for anti-inflammatory therapy of acute lung injury (ALI). Cholesterol was conjugated to histidine- and arginine-grafted polyamidoamine (PamHR) for micelle formation. The cholesterol-conjugated PamHR (PamHRchol) was mixed with amphiphilic GA to produce PamHRchol/GA mixed micelles.

Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Phospholipid Changes in a Model of Early Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a degenerative disease caused by motor neuron damage in the central nervous system, and it is difficult to diagnose early. is widely used to investigate disease mechanisms and discover biomarkers because it is easy to induce disease in through genetic engineering. We performed matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to investigate changes in phospholipid distribution in the brain tissue of an ALS-induced model.

Apoptin gene delivery by a PAMAM dendrimer modified with a nuclear localization signal peptide as a gene carrier for brain cancer therapy.

In this study, we aimed to synthesize PAMAMG3 derivatives (PAMAMG3-KRRR and PAMAMG3-HKRRR), using KRRR peptides as a nuclear localization signal and introduced histidine residues into the KRRR-grafted PAMAMG3 for delivering a therapeutic, carcinoma cell-selective apoptosis gene, apoptin into human primary glioma (GBL-14) cells and human dermal fibroblasts. We examined their cytotoxicity and gene expression using luciferase activity and enhanced green fluorescent protein PAMAMG3 derivatives in both cell lines. We treated cells with PAMAMG3 derivative/apoptin complexes and investigated their intracellular distribution using confocal microscopy.

Preparation and characterization of 3D human glioblastoma spheroids using an N-octanoyl glycol chitosan hydrogel.

The current 2D culture model systems developed for drug screening are not sufficient to reflect the characteristics of in vivo solid tumors. Therefore, more effective in vitro tumor model systems must be developed for translational studies on therapeutic drug screening and testing. Herein, we report a new ultra-low adhesion (ULA) hydrogel for generating 3D cancer cell spheroids as tumor models in vitro.

Nonviral gene delivery using PAMAM dendrimer conjugated with the nuclear localization signal peptide derived from human papillomavirus type 11 E2 protein.

Polyamidoamine (PAMAM) dendrimers are biocompatible polymers utilized in multiple biomedical applications including tissue engineering, medical diagnosis, drug and gene delivery systems, and biosensors. Normally, high-generation PAMAM dendrimers are advantageous for use in gene therapy research because they have a relatively high transfection efficiency. A high-generation PAMAM dendrimer has a high charge density, which induces greater damage to the membranous organelles than that induced by a low-generation PAMAM dendrimer.

Crystal structure of human LC8 bound to a peptide from Ebola virus VP35.

Zaire ebolavirus, commonly called Ebola virus (EBOV), is an RNA virus that causes severe hemorrhagic fever with high mortality. Viral protein 35 (VP35) is a virulence factor encoded in the EBOV genome. VP35 inhibits host innate immune responses and functions as a critical cofactor for viral RNA replication.

Triphenylphosphonium-conjugated glycol chitosan microspheres for mitochondria-targeted drug delivery.

To develop an efficient vector for mitochondria-targeted drug delivery, we synthesized triphenylphosphonium (TPP)-modified glycol chitosan polymeric microspheres that had a unique chemical structure with both lipophilic phenyl groups and cationic phosphonium. Notably, TPP can easily pass through the phospholipid bilayer of mitochondria, thereby resulting in specific accumulation of a combined drug molecule in the mitochondria due to the membrane potential between TPP and its membrane. Therefore, TPP has been widely used as a mitochondria-targeting moiety.

Brain gene delivery using histidine and arginine-modified dendrimers for ischemic stroke therapy.

Polyamidoamine dendrimer has been studied as an efficient gene carrier. Due to its anti-inflammatory properties, polyamidoamine is a useful gene carrier, especially for inflammatory diseases. However, the commonly used polyamidoamine generation 6 dendrimer (PG6) has higher cytotoxicity than low-molecular weight polyamidoamines, which limits its applications.

Cathepsin B-Responsive Liposomes for Controlled Anticancer Drug Delivery in Hep G2 Cells.

In recent decades, several types of anticancer drugs that inhibit cancer cell growth and cause cell death have been developed for chemotherapeutic application. However, these agents are usually associated with side effects resulting from nonspecific delivery, which may induce cytotoxicity in healthy cells. To reduce the nonspecific delivery issue, nanoparticles have been successfully used for the delivery of anticancer drugs to specific target sites.

Enhanced transfection efficiency of low generation PAMAM dendrimer conjugated with the nuclear localization signal peptide derived from herpesviridae.

Polyamidoamine (PAMAM) dendrimer is an extensively studied polymer in the biomedical research because of its low polydispersity, distinct molecular structure, and surface functionalities. Generally, a high-generational PAMAM dendrimer is used for gene delivery because transfection efficiency is dependent on charge density; however, an increase in charge density induces disruption of the cellular membrane, and damage to the membrane results in cytotoxicity. In this study, we selected PAMAM generation 2 to reduce the cytotoxic effect and conjugated RRILH and RRLHL sequences, nuclear localization signals (NLS) derived from herpesviridae to PAMAM generation 2.

Antibacterial Film Formation through Iron(III) Complexation and Oxidation-Induced Cross-Linking of -DOPA.

Catechols are prone to oxidative polymerization as well as complex formation with metal ions. These two features of catechols have played an important role in the construction of functional films on various surfaces. For example, marine antifouling films and antibacterial films were successfully prepared by oxidative polymerization and metal complexation of catechol-containing molecules, respectively.

Polyplexes of Functional PAMAM Dendrimer/Apoptin Gene Induce Apoptosis of Human Primary Glioma Cells In Vitro.

Highly efficient and safe gene delivery has become an important aspect of neuronal gene therapy. We evaluated the ability of polyamidoamine (PAMAM) dendrimer grafted with phenylalanine, histidine, and arginine (PAMAM-FHR), a nonviral gene delivery vector, to deliver a therapeutic, tumor cell-specific killer gene, apoptin, into the human primary glioma cell line GBL-14 and human dermal fibroblasts. We performed a transfection assay using plasmids of luciferase and enhanced green fluorescent protein (EGFP) and assessed cell viability.