Magnetic resonance image-guided focused ultrasound has emerged as a viable non-invasive technique for the treatment of central nervous system-related diseases/disorders. Application of mechanical and thermal effects associated with focused transcranial ultrasound has been studied extensively in pre-clinical models, which has paved the way for clinical trials. However, in vivo treatment evaluation techniques on drug delivery application via blood-brain barrier opening has not been fully explored.
View Article and Find Full Text PDFThe blood-brain barrier (BBB) limits transport of nanoparticles from the circulation to the brain parenchyma. Angiopep-2, a peptide which functions as a brain transport vector, can be coupled to nanoparticles in order to facilitate binding and internalization by brain endothelial cells (ECs), and subsequent BBB penetration. This multi-step process may be affected by blood flow over brain ECs, as flow influences endothelial cell phenotype as well as interactions of nanoparticles with ECs.
View Article and Find Full Text PDFThermal ablation of solid tumors via focused ultrasound (FUS) is a non-invasive image-guided alternative to conventional surgical resection. However, the usefulness of the technique is limited in vascularized organs because of convection of heat, resulting in long sonication times and unpredictable thermal lesion formation. Acoustic cavitation has been found to enhance heating but requires use of exogenous nuclei and sufficient acoustic monitoring.
View Article and Find Full Text PDFFocused ultrasound (FUS) has the potential to enable precise, image-guided noninvasive surgery for the treatment of cancer in which tumors are identified and destroyed in a single integrated procedure. However, success of the method in highly vascular organs has been limited due to heat losses to perfusion, requiring development of techniques to locally enhance energy absorption and heating. In addition, FUS procedures are conventionally monitored using MRI, which provides excellent anatomical images and can map temperature, but is not capable of capturing the full gamut of available data such as the acoustic emissions generated during this inherently acoustically-driven procedure.
View Article and Find Full Text PDFBrain drug delivery is a major challenge for therapy of central nervous system (CNS) diseases. Biochemical modifications of drugs or drug nanocarriers, methods of local delivery, and blood-brain barrier (BBB) disruption with focused ultrasound and microbubbles are promising approaches which enhance transport or bypass the BBB. These approaches are discussed in the context of brain cancer as an example in CNS drug development.
View Article and Find Full Text PDFDesigning of drug nanocarriers to aid delivery of therapeutics is an expanding field that can improve medical treatments. Nanocarriers are often functionalized with elements that recognize cell-surface molecules involved in subcellular transport to improve targeting and endocytosis of therapeutics. Combination-targeting using several affinity elements further modulates this outcome.
View Article and Find Full Text PDFTargeting of drug carriers to cell-surface receptors involved in endocytosis is commonly used for intracellular drug delivery. However, most endocytic receptors mediate uptake via clathrin or caveolar pathways associated with ≤200-nm vesicles, restricting carrier design. We recently showed that endocytosis mediated by intercellular adhesion molecule 1 (ICAM-1), which differs from clathrin- and caveolae-mediated pathways, allows uptake of nano- and microcarriers in cell culture and in vivo due to recruitment of cellular sphingomyelinases to the plasmalemma.
View Article and Find Full Text PDFModification of drug delivery nanomaterials with affinity molecules that facilitate targeting, has rendered a new class of ligands for cell receptors, which often possess valency and dimensions different from natural counterparts. Designing strategies to target multiple receptors or, never explored, multiple epitopes on the same receptor may modulate the biodistribution properties of these nanomaterials. We examined this using antibody-directed targeting of polymer nanocarriers to transferrin receptor (TfR) and intercellular adhesion molecule 1 (ICAM-1).
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