Extracellular nanovesicles (ENV) released by many cells contain lipids, proteins, and nucleic acids that contribute to intercellular communication. ENVs have emerged as biomarkers and therapeutic targets but they have also been explored as drug delivery vehicles. However, for the latter application, clinical translation has been limited by low yield and inadequate targeting effects. ENV vectors with desired targeting properties can be produced from parental cells engineered to express membrane-bound targeting ligands, or they can be generated by fusion with targeting liposomes; however, neither approach has met clinical requirements. In this study, we demonstrate that mechanical extrusion of approximately 10 cells grafted with lipidated ligands can generate cancer cell-targeting ENV and can be prepared in approximately 1 hour. This rapid and economic approach could pave the way for clinical implementation in the future. A new and rapid method for production of drug-targeting nanovesicles has implications for cancer treatment by chimeric antigen receptor T cells and other therapies. .

Summary Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. CTCs hold the key to understanding the biology of metastasis and also play a vital role in cancer diagnosis, prognosis, disease monitoring, and personalized therapy. However, CTCs are rare in blood and hard to isolate. Additionally, the viability of CTCs can easily be compromised under high shear stress while releasing them from a surface. The heterogeneity of CTCs in biomarker expression makes their isolation quite challenging; the isolation efficiency and specificity of current approaches need to be improved. Nanostructured substrates have emerged as a promising biosensing platform since they provide better isolation sensitivity at the cost of specificity for CTC isolation. This review discusses major challenges faced by CTC isolation techniques and focuses on nanostructured substrates as a platform for CTC isolation.

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