Yeast cell wall particles for receptor-targeted nanoparticle delivery

Abstract

The present invention generally relates to yeast cell wall microparticles loaded with nanoparticles for receptor-targeted nanoparticle delivery. In particular, the present invention relates to trapping nanoparticles either on the surface or inside a yeast glucan particles, for example, yeast glucal particles. The present invention further relates to methods of making the yeast cell wall particles loaded with nanoparticles. The present invention also relates to methods of using the yeast cell wall particles particles loaded with nanoparticles for receptor-targeted delivery of the nanoparticles, e.g., drug containing nanoparticles.

1 . A yeast cell wall particle-nanoparticle (YCWP-NP) delivery system, comprising yeast cell wall particles (YCWPs) comprising nanoparticles (NPs) having at least one dimension of about 1-40 nm contained within the interior of the YCWPs, wherein the YCWP-NP delivery system is prepared by a process comprising the steps of:
 (a) loading the NPs into the YCWPs, wherein the loading comprises incubating a suspension comprising YCWPs and NPs for a time sufficient for the NPs to enter into the YCWPs,   (b) drying the material resulting from (a),   (c) optionally repeating steps (a)-(b) at least once,   (d) resuspending the YCWPs and nanoparticles in solvent for a time sufficient for additional NPs to enter into the YCWPs,   (e) optionally drying the material resulting from (d), and   (f) optionally trapping the NPs in the YCWPs using an appropriate trapping means, such that the YCWP-NP delivery system is prepared.   
     
     
         2 . The YCWP-NP delivery system of  claim 1 , wherein:
 the NPs have at least one dimension of about 2-40 nm, of about 5-30 nm or of about 10-30 nm;   the YCWPs are selected from the group consisting of YGPs, YGMPs, YCPs and YGCPs;   the loading comprises incubating the suspension for about 1-2 hours;   the solvent is saline or water;   the nanoparticles are selected from the group consisting of quantum dots, gold particles and magnetic particles; or   the trapping means is selected from the group consisting of a physical trapping means, an electrostatic trapping means, an affinity trapping means, and a hydrophobic trapping means.   
     
     
         3 - 11 . (canceled) 
     
     
         12 . The YCWP-NP delivery system of  claim 2 , wherein the electrostatic trapping results from interaction of the nanoparticle with a cationic polymeric trapping molecule that is optionally PEI. 
     
     
         13 . (canceled) 
     
     
         14 . The YCWP-NP delivery system of  claim 2 , wherein the physical trapping results from interaction of the nanoparticle with a trapping molecule selected from the group consisting of tRNA, alginate and chitosan. 
     
     
         15 . A yeast cell wall particle-nanoparticle (YCWP-NP) delivery system, comprising yeast cell wall particles (YCWPs) comprising nanoparticles (NPs) having at least one dimension of about 10-1000 nm on the surface of the YCWPs, wherein the YCWP delivery system is prepared by a process comprising the steps of:
 (a) loading the NPs onto the YCWPs, wherein the loading comprises incubating a suspension comprising YCWPs and NPs for a time sufficient for the NPs to bind to the YCWPs, wherein the YCWPs are surface-derivatized such that NP binding is facilitated,   (b) washing and/or dispersing the material resulting from (a) and   (c) optionally repeating steps (a)-(b) at least once, such that the YCWP-NP delivery system is prepared.   
     
     
         16 . The YCWP-NP delivery system of  claim 15 , wherein the NPs have at least one dimension of about 10-100 nm, of about 100-500 nm, or of about 500-1000 nm. 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The YCWP-NP delivery system of  claim 15 , wherein the YCWPs are selected from the group consisting of YGPs, YGMPs, YCPs and YGCPs. 
     
     
         20 . The YCWP-NP delivery system of  claim 19 , wherein the YCWPs are YGPs. 
     
     
         21 . The YCWP-NP delivery system of  claim 15 , wherein the loading comprises incubating the suspension for about 12-24 hours. 
     
     
         22 . The YCWP-NP delivery system of  claim 15 , wherein the surface-derivatized YCPWs are derivatized to have an electrostatic surface or a cationic surface 
     
     
         23 . (canceled) 
     
     
         24 . The YCWP-NP delivery system of  claim 22 , wherein the surface-derivatized YCPWs are derivatized to have an anionic surface. 
     
     
         25 . The YCWP-NP delivery system of  claim 15 , wherein the surface-derivatized YCPWs are derivatized to facilitate covalent or affinity binding of the NPs to the surface. 
     
     
         26 . The YCWP-NP delivery system of  claim 15 , wherein the surface-derivatized YCPWs are derivatized to facilitate biotin-streptavidin binding of NPs to the surface. 
     
     
         27 . The YCWP-NP delivery system of  claim 22 , wherein the YCWPs have a trapping polymer covalently linked to the surface. 
     
     
         28 . The YCWP-NP delivery system of  claim 29 , wherein the trapping polymer is selected from the group consisting of polyethyleneamine (PEI), polylysine (PLL) and chitosan. 
     
     
         29 . The YCWP-NP delivery system of  claim 15 , wherein the nanoparticles are selected from the group consisting of quantum dots, gold particles and magnetic particles. 
     
     
         30 . A method of using the YCWP-NP delivery system of  claim 1  in drug delivery. 
     
     
         31 . A method of using the YCWP-NP delivery system of  claim 1  in medical imaging. 
     
     
         32 . A method for making the YCWP-NP delivery system of  claim 1  comprising performing the steps recited.