Intracellular Nanodelivery of DNA with Enzyme-Degradable and pH-Responsive Peptide Dendrons.

Effective DNA delivery requires functional materials to package and transport genetic cargo into cells. However, many synthetic systems rely on heterogeneous mixtures, lack biodegradability, and pose toxicity concerns. Here, we introduce a peptide dendron single-molecule transfection reagent that enables targeted DNA delivery via pH-responsive, degradable nanoparticles with minimal toxicity.

Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation.

Oral delivery of peptides and biological molecules promises significant benefits to patients as an alternative to daily injections, but the development of these formulations is challenging due to their low bioavailability and high pharmacokinetic variability. Our earlier work focused on the discovery of MEDI7219, a stabilized, lipidated, glucagon-like peptide 1 agonist peptide, and the selection of sodium chenodeoxycholate (Na CDC) and propyl gallate (PG) as permeation enhancer combinations. We hereby describe the development of the MEDI7219 tablet formulations and composition optimization via in vivo studies in dogs.

Engineered Ultrasmall Nanoparticle Drug-Immune Conjugates with "Hit and Run" Tumor Delivery to Eradicate Gastric Cancer.

Despite advances by recently approved antibody-drug conjugates in treating advanced gastric cancer patients, substantial limitations remain. Here, several key obstacles are overcome by developing a first-in-class ultrasmall (sub-8-nanometer (nm)) anti-human epidermal growth factor receptor 2 (HER2)-targeting drug-immune conjugate nanoparticle therapy. This multivalent fluorescent core-shell silica nanoparticle bears multiple anti-HER2 single-chain variable fragments (scFv), topoisomerase inhibitors, and deferoxamine moieties.

Sensitive Colorimetric Detection of Interleukin-6 Lateral Flow Assay Incorporated Silver Amplification Method.

Interleukin-6 (IL-6) is a pro/anti-inflammatory cytokine, the quantitative detection of which has been extensively considered for diagnosis of inflammatory associated diseases. However, there has not yet been a reliable, low-cost, and user-friendly platform developed for point-of-care (POC) detection of IL-6, which will eliminate the conventional costly, time-consuming, and complex assays. In this work, we developed a lateral flow assay for colorimetric detection of IL-6, using anti-IL-6 antibodies conjugated to gold nanoparticles (AuNPs) as the detection probes.

Development of an orally delivered GLP-1 receptor agonist through peptide engineering and drug delivery to treat chronic disease.

Peptide therapeutics are increasingly used in the treatment of disease, but their administration by injection reduces patient compliance and convenience, especially for chronic diseases. Thus, oral administration of a peptide therapeutic represents a significant advance in medicine, but is challenged by gastrointestinal instability and ineffective uptake into the circulation. Here, we have used glucagon-like peptide-1 (GLP-1) as a model peptide therapeutic for treating obesity-linked type 2 diabetes, a common chronic disease.