Flash drug release from nanoparticles accumulated in the targeted blood vessels facilitates the tumour treatment

Abstract

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.

Electrically Triggered Quercetin Release from Polycaprolactone/Bismuth Ferrite Microfibrous Scaffold for Skeletal Muscle Tissue

“…It was revealed that the application of an electric field induced rapid release of the drug. The expedited delivery of therapeutic agents to the injury site through rapid drug release may provide improved drug efficiency [ 53 ]. This attribute is especially crucial in scenarios where a limited time window exists to facilitate regeneration, as is the case with acute injuries.…”

Design and fabrication of intracellular therapeutic cargo delivery systems based on nanomaterials: current status and future perspectives

“…For instance, Mondal et al developed two polymerbased micellar NPs containing mannose-6-phosphate glycopolypeptide (M6P) its surface, which were selectively taken up by receptor-mediated endocytosis and then transported to lysosomes where subsequently degraded by pH or enzymes. 194 195 (Fig. 23).…”

“…23 (A) Left panel: Systemic administration in mice, with NPs sequestered in capillaries in metastatic lung tissue (tumor cells are shown in purple).Right panel: The metal-organic framework, which rapidly enters the pulmonary capillaries and anchors to the endothelium to begin releasing the drug (shown in green), spreading to metastatic nodes and destroying the cancer cells 195. (B) Schematic representation of the MIL-101 NPs as well as a scanning electron microscopy (SEM) micrograph 195. (C) Representative confocal images of the distribution of MIL-101 NP in lung tissue at 15 min,1 h, and 3 h after systemic administration195…”

“…(B) Schematic representation of the MIL-101 NPs as well as a scanning electron microscopy (SEM) micrograph 195. (C) Representative confocal images of the distribution of MIL-101 NP in lung tissue at 15 min,1 h, and 3 h after systemic administration195…”

Influence of magnetic nanoparticle biotransformation on contrasting efficiency and iron metabolism

“…Usually, the process of nanoparticle elimination from the body is analyzed by measuring concentration of their components using mass spectrometry [ 15 , 16 ]. However, this method does not allow tracking the processes of the internal transformations of the nanoparticles, for example, changes in their crystal structure and magnetic properties.…”