Tumour microenvironment hinders nanoparticle transport deep into the tissue precluding thorough treatment of solid tumours and metastatic nodes. We introduce an anticancer drug delivery concept termed FlaRE (Flash Release in Endothelium), which represents alternative to the existing approaches based on enhanced permeability and retention effect. This approach relies on enhanced drug-loaded nanocarrier accumulation in vessels of the target tumour or metastasised organ, followed by a rapid release of encapsulated drug within tens of minutes. It leads to a gradient-driven permeation of the drug to the target tissue. This pharmaceutical delivery approach is predicted by theoretical modelling and validated experimentally using rationally designed MIL-101(Fe) metal-organic frameworks. Doxorubicin-loaded MIL-101 nanoparticles get swiftly trapped in the vasculature of the metastasised lungs, disassemble in the blood vessels within 15 minutes and release drug, which rapidly impregnates the organ. A significant improvement of the therapeutic outcome is demonstrated in animal models of early and late-stage B16-F1 melanoma metastases with 11-fold and 4.3-fold decrease of pulmonary melanoma nodes, respectively.

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The aim of the investigation was to study the potential of an innovative microfluidic technology for the isolation of circulating tumor cells (CTCs) from the peripheral blood samples of cancer patients.Materials and Methods. Peripheral blood samples from 5 patients with disseminated malignant tumors of epithelial origin were processed with the use of the microfluidic technology (based on a specifically designed silicone chip). The cells were separated according to their density criterion based on the lateral migration of solid particles in a liquid due to inertial forces. With the help of the designed chip configuration, the cells over 13 μm in size which is larger than the standard size of blood cells were isolated. The resulting target cell fraction was stained by the Romanowsky-Giemsa method. Staining with the fluorescent Anti-Cytokeratin (CK3-6H5)-FITC antibody was carried out to confirm the epithelial nature of the cells, and the DAPI dye was used to contrast the nucleus. The blood of a healthy volunteer and tumor cells of the A549 line were used for the immunocytochemical studies.Results. The tumor cells in peripheral blood (in the number of 1 to 9) were detected in all 5 patients. CTC clusters of 2-5 cells were identified in blood samples from the patients with laryngeal cancer, non-small cell lung cancer, and floor of the mouth cancer. A bright saturated staining of the A549 tumor cells was obtained using the Anti-Cytokeratin (CK3-6H5)-FITC antibody, corresponding to the staining of the cytoskeleton of epithelial cells. Successful nuclear staining with DAPI confirmed that the isolated target cells are not damaged during microfluidic separation.Conclusion. The microfluidic technology that has been used enables effective intact CTCs isolating from the peripheral blood of cancer patients. The epithelial nature of the isolated cells can be confirmed by immunocytochemical studies.

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