Extracellular Vesicles as Next-Generation Diagnostics and Advanced Therapy Medicinal Products.

Extracellular vesicles (EVs) hold great promise for clinical application as new diagnostic and therapeutic modalities. This paper describes major GMP-based upstream and downstream manufacturing processes for EV large-scale production, also focusing on post-processing technologies such as surface bioengineering and uploading studies to yield novel EV-based diagnostics and advanced therapy medicinal products. This paper also focuses on the quality, safety, and efficacy issues of the bioengineered EV drug candidates before first-in-human studies.

Surface-Bioengineered Extracellular Vesicles Seeking Molecular Biotargets in Lung Cancer Cells.

Personalized medicine is a new approach to modern oncology. Here, to facilitate the application of extracellular vesicles (EVs) derived from lung cancer cells as potent advanced therapy medicinal products in lung cancer, the EV membrane was functionalized with a specific ligand for targeting purposes. In this role, the most effective heptapeptide in binding to lung cancer cells (PTHTRWA) was used.

Lack of cytotoxic and genotoxic effects of mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium despite cellular uptake in cancerous and noncancerous lung cells.

Cytotoxic and genotoxic effects of novel mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium (Mg-γ-FeO(mPEG-silane)) have been investigated on human adenocarcinomic alveolar basal epithelial (A549) and human normal bronchial epithelial (BEAS-2B) cells. In the studies several molecular and cellular targets addressing to cell membrane, cytoplasm organelles and nucleus components were served as toxicological endpoints. The as-synthesized nanoparticles were found to be stable in the cell culture media and were examined for different concentration and exposure times.

Extracellular Vesicles as Next-Generation Biomarkers in Lung Cancer Patients: A Case Report on Adenocarcinoma and Squamous Cell Carcinoma.

Extracellular vesicles (EVs) released from primary cell lines, originating from resected tissues during biopsies in patients with non-small cell lung cancer (NSCLC) revealing adenocarcinoma and squamous cell carcinoma subtypes, were examined for membrane proteomic fingerprints using a proximity barcoding assay. All the collected EVs expressed canonical tetraspanins (CD9, CD63, and CD81) highly coexpressed with molecules such as lysosome-associated membrane protein-1 (LAMP1-CD107a), sialomucin core protein 24 (CD164), Raph blood group (CD151), and integrins (ITGB1 and ITGA2). This representation of the protein molecules on the EV surface may provide valuable information on NSCLC subtypes and offer new diagnostic opportunities as next-generation biomarkers in personalized oncology.

Oxidation-derived anticancer potential of sumanene-ferrocene conjugates.

An effective synthetic protocol towards the oxidation of sumanene-ferrocene conjugates bearing one to four ferrocene moieties has been established. The oxidation protocol was based on the transformation of Fe from ferrocene to Fe-containing ferrocenium cations by means of the treatment of the title organometallic buckybowls with a mild oxidant. Successful isolation of these ferrocenium-tethered sumanene derivatives 5-7 gave rise to the biological evaluation of the first, buckybowl-based anticancer agents, as elucidated by assays with human breast adenocarcinoma cells (MDA-MB-231) and embryotoxicity trials in zebrafish embryos supported with toxicology studies.