Particles for cell targeting
Provided is a composition that includes oblate spheroidal particles comprising an active agent, such as a therapeutic or imaging agent, and a method for treating or monitoring a physiological condition, such as a disease, by administering the composition to a subject in need thereof. Also provided are methods for making particles that have a volume that can enhance the particles' adhesion to a target site in a subject's body for a pre-selected shape of the particles and methods for making particles that have a shape that can enhance particles' adhesion to a target site in a subject's body for a pre-selected volume of the particles.
1. A method of designing and fabricating particles having an enhanced adherence to cells of a target site, the method comprising
(A) selecting a target site having a surface, said surface having one or more first moieties;
(B) selecting second moieties that are capable of binding to the first moieties;
(C) selecting a numerical value for a spheroid aspect ratio of a spheroidal particle;
(D) calculating the numerical value of volume that maximizes the adherence strength of the spheroidal particle to the target site using the following input parameters; (i) the selected numerical value of the spheroid aspect ratio; (ii) the area of interaction ¶r 0 2 between the spheroidal particle and the target site, where r 0 is the radius of the spheroidal particle; and (iii) the numerical value of the surface density of the first moieties on the target site, wherein the volume of the spheroidal particle (V) is related to the aspect ratio (γ) as V=4/3¶a 3 γ −1 , and γ=a/b, where a and b represent half-lengths of two axes of the spheroidal particle, and γ≧1;
(E) fabricating the spheroidal particle, that has a spheroid aspect ratio substantially equal to the selected numerical value and a volume that has a numerical value that is substantially equal to the calculated numerical value of the maximizing volume; and
(F) disposing the second moieties on a surface of the particle
wherein the particles obtained have an enhanced adherence to cells of the target site.
2. The method of claim 1 , wherein the target site is a vascular site comprising coopted vasculature, an angiogenic vasculature or a renormalized vasculature.
3. The method of claim 1 , wherein said first moieties are selected from the group consisting of angiopoietin 2 receptors, vascular endothelial growth factors, basic fibroblast growth factors, endothelial markers, carcinoembryonic-related cell adhesion molecules 1, endothelin-B receptor, AKAP12, and scaffolding proteins.
4. The method of claim 1 , wherein said second moieties comprise ligands, aptamers or antibodies.