Advances in Drug Delivery Systems Based on Red Blood Cells and Their Membrane-Derived Nanoparticles.

Red blood cells (RBCs) and RBC membrane-derived nanoparticles have been historically developed as bioinspired drug delivery systems to combat the issues of premature clearance, toxicity, and immunogenicity of synthetic nanocarriers. RBC-based delivery systems possess characteristics including biocompatibility, biodegradability, and long circulation time, which make them suited for systemic administration. Therefore, they have been employed in designing optimal drug formulations in various preclinical models and clinical trials to treat a wide range of diseases.

Endosomal escape of nucleic acids from extracellular vesicles mediates functional therapeutic delivery.

Extracellular vesicles hold great promise as a drug delivery platform for RNA-based therapeutics. However, there is a lack of experimental evidence for the intracellular trafficking of nucleic acid cargos, specifically, whether they are capable of escaping from the endolysosomal confinement in the recipient cells to be released into the cytosol and hence, interact with their cytoplasmic targets. Here, we demonstrated how red blood cell-derived extracellular vesicles (RBCEVs) release their therapeutic RNA/DNA cargos at specific intracellular compartments characteristic of late endosomes and lysosomes.

Immunological Hallmarks for Clinical Response to BCG in Bladder Cancer.

Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumor activity.