Drug repositioning of mesalamine via supramolecular nanoassembly for the treatment of drug-induced acute liver failure.

Acute liver failure (ALF) is characterized by rapid hepatic dysfunction, primarily caused by drug-induced hepatotoxicity. Due to the lack of satisfactory treatment options, ALF remains a fatal clinical disease, representing a grand challenge in global health. For the drug repositioning to ALF of mesalamine, which is clinically approved for the treatment of inflammatory bowel disease (IBD), we propose a supramolecular prodrug nanoassembly (SPNs).

Targeted delivery of anti-miRNA21 sensitizes PD-L1 tumor to immunotherapy by promoting immunogenic cell death.

Growing evidence has demonstrated that miRNA-21 (miR-21) upregulation is closely associated with tumor pathogenesis. However, the mechanisms by which miR-21 inhibition modulates the immunosuppressive tumor microenvironment (TME) and improves tumor sensitivity to immune checkpoint blockade therapies remain largely unexplored. In this study, we demonstrate the precise delivery of anti-miR-21 using a PD-L1-targeting peptide conjugate (P21) to the PD-L1 TME.

Design of PD-L1-Targeted Lipid Nanoparticles to Turn on PTEN for Efficient Cancer Therapy.

Lipid nanoparticles (LNPs) exhibit remarkable mRNA delivery efficiency, yet their majority accumulate in the liver or spleen after injection. Tissue-specific mRNA delivery can be achieved through modulating LNP properties, such as tuning PEGylation or varying lipid components systematically. In this paper, a streamlined method is used for incorporating tumor-targeting peptides into the LNPs; the programmed death ligand 1 (PD-L1) binding peptides are conjugated to PEGylated lipids via a copper-free click reaction, and directly incorporated into the LNP composition (Pep LNPs).

Post-insertion technique to introduce targeting moieties in milk exosomes for targeted drug delivery.

Background: Recently, increased attention has been given on exosomes as ideal nanocarriers of drugs owing to their intrinsic properties that facilitate the transport of biomolecular cargos. However, large-scale exosome production remains a major challenge in the clinical application of exosome-based drug delivery systems. Considering its biocompatibility and stability, bovine milk is a suitable natural source for large-scale and stable exosome production.

mRNA: A promising platform for cancer immunotherapy.

Messenger RNA (mRNA) is now in the limelight as a powerful tool for treating various human diseases, especially malignant tumors, thanks to the remarkable clinical outcomes of mRNA vaccines using lipid nanoparticle technology during the COVID-19 pandemic. Recent promising preclinical and clinical results that epitomize the advancement in mRNA and nanoformulation-based delivery technologies have highlighted the tremendous potential of mRNA in cancer immunotherapy. mRNAs can be harnessed for cancer immunotherapy in forms of various therapeutic modalities, including cancer vaccines, adoptive T-cell therapies, therapeutic antibodies, and immunomodulatory proteins.

The Potential of Cell-Penetrating Peptides for mRNA Delivery to Cancer Cells.

In vitro transcribed mRNA for the synthesis of any given protein has shown great potential in cancer gene therapy, especially in cancer vaccines for immunotherapy. To overcome physiological barriers, such as rapid degradation by enzymatic attack and poor cellular uptake due to their large size and hydrophilic properties, many delivery carriers for mRNAs are being investigated for improving the bioavailability of mRNA. Recently, cell-penetrating peptides (CPPs) have received attention as promising tools for gene delivery.

The Effect of Neddylation Blockade on Slug-Dependent Cancer Cell Migration Is Regulated by p53 Mutation Status.

The tumor suppressor protein p53 is frequently inactivated in human malignancies, in which it is associated with cancer aggressiveness and metastasis. Because p53 is heavily involved in epithelial-mesenchymal transition (EMT), a primary step in cell migration, p53 regulation is important for preventing cancer metastasis. p53 function can be modulated by diverse post-translational modifications including neddylation, a reversible process that conjugates NEDD8 to target proteins and inhibits the transcriptional activity of p53.