Particle compositions with a pre-selected cell internalization mode

A method of formulating a particle composition having a pre-selected cell internalization mode involves selecting a target cell having surface receptors and obtaining particles that have i) surface moieties, that have an affinity for or are capable of binding to the surface receptors of the cell and ii) a preselected shape, where a surface distribution of the surface moieties on the particles and the shape of the particles are effective for the pre-selected cell internalization mode

The transport of nanoparticles in blood vessels: the effect of vessel permeability and blood rheology

The longitudinal transport of nanoparticles in blood vessels has been analyzed with blood described as a Casson fluid. Starting from the celebrated Taylor and Aris theory, an explicit expression has been derived for the effective longitudinal diffusion (Deff) depending non-linearly on the rheological parameter xi(c), the ratio between the plug and the vessel radii; and on the permeability parameters pi and omega, related to the hydraulic conductivity and pressure drop across the vessel wall, respectively. An increase of xi(c) or pi has the effect of reducing Deff, and thus both the rheology of blood and the permeability of the vessels may constitute a physiological barrier to the intravascular delivery of nanoparticles

Unraveling the vascular fate of deformable circulating tumor cells via a hierarchical computational model

Distant spreading of primary lesions is modulated by the vascular dynamics of circulating tumor cells (CTCs) and their ability to establish metastatic niches. While the mechanisms regulating CTC homing in specific tissues are yet to be elucidated, it is well documented that CTCs possess different size, biological properties and deformability. A computational model is presented to predict the vascular transport and adhesion of CTCs in whole blood. A Lattice-Boltzmann method, which is employed to solve the Navier-Stokes equation for the plasma flow, is coupled with an Immersed Boundary Method. The vascular dynamics of a CTC is assessed in large and small microcapillaries. The CTC shear modulus k ctc is varied returning CTCs that are stiffer, softer and equally deformable as compared to RBCs. In large microcapillaries, soft CTCs behave similarly to RBCs and move away from the vessel walls; whereas rigid CTCs are pushed laterally by the fast moving RBCs and interact with the vessel walls. Three adhesion behaviors are observed, firm adhesion, rolling and crawling over the vessel walls, depending on the CTC stiffness. On the contrary, in small microcapillaries, rigid CTCs are pushed downstream by a compact train of RBCs and cannot establish any firm interaction with the vessel walls; whereas soft CTCs are squeezed between the vessel wall and the RBC train and rapidly establish firm adhesion. These findings document the relevance of cell deformability in CTC vascular adhesion and provide insights on the mechanisms regulating metastasis formation in different vascular districts

Nanomedicine

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Intravascular Delivery of Particulate Systems: Does Geometry Really Matter?

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A microfluidic platform with permeable walls for the analysis of vascular and extravascular mass transport

Considerable advances have been made in microfluidic devices and their applications since the development of soft lithographic techniques [1]. We developed a PDMS based double channel chip consisting of two microfluidic channels that mimic the vascular and extravascular compartments. The two channels are designed to be confined by sidewalls and connected by a membrane composed by arrays of pillars constituting a permeable vascular wall [2]. The inner surface of the vascular channel is uniformly coated with Human Umbilical Vein Endothelial Cells (HUVEC) resulting in well-controlled 3D model of blood vessel with endothelial barrier functions. In Figure.1A and B, the photolithographic, etching, and replica molding steps needed for realizing double-channel chips are presented together with an image (right) of the vascular channel after cell seeding and self-organization in a tubular shape. The extravascular compartment can be integrated with tumor cells of different type, potentially organized in a 3D fashion inside an extracellular matrix or with extracellular matrix components. The integration of the two compartments allow us to study the transport and permeation of therapeutic molecules, nanomedicines and cells through the endothelial barrier and the efficacy of the administered treatment. Other applications such as modeling of metastatic cell and leucocytes adhesion and migration across the endothelial barrier allow us to characterize cell extravasation from the vascular bed. The vascular transport and subsequent adhesion dynamics of nano-constructs and cells to the vascular channel are also predicted using a 3D computational framework based on coupling Lattice Boltzmann (LB) and Immersed Boundary (IB) methods. The fluid solver for the incompressible Navier-Stokes equations is based on the three dimensional D3Q19 Lattice-Boltzmann Method. The dynamics of deformable nano-constructs and cells is simulated through a neo-Hookean membrane constitutive model coupled iteratively with the fluid (Figure.1C). The combination of microfluidic chips and computational modeling provides a formidable tool for boosting our understanding on disease development and drug delivery. Please click Additional Files below to see the full abstract