Nanoparticle probes and methods of making and use thereof

Abstract

Some embodiments relate to nanoparticle probes for the detection of disease states in a patient or for tissue engineering. In some embodiments, the nanoparticle probe comprises one or more slip bonds that bind to a cell surface structure. In some embodiments, the binding of the nanoparticle probe is selective. In some embodiments, the nanoparticle probe binds to cells having a certain maximum glycocalyx thickness.

What is claimed is: 
     
         1 . A nanoparticle probe comprising:
 a nanoparticle base structure; and   a slip bond moiety configured to reversibly bind to a glycocalyx of a cell;   a tether functionalized to the nanoparticle base structure and to an associative moiety configured to bind to a one or more of a cell surface protein, receptor, and/or biomarker of the cell;   wherein the associative moiety preferentially binds to the protein, receptor, and/or biomarker of the cell based on the thickness of a glycocalyx layer of the cell.   
     
     
         2 . The nanoparticle probe of  claim 1 , wherein the slip bond has a binding strength of less than about 100 pN. 
     
     
         3 . The nanoparticle probe of  claim 1 , wherein the associative moiety has a binding strength of larger than 100 pN. 
     
     
         4 . The nanoparticle probe of  claim 1 , wherein the associative moiety comprises a ligand for a cell surface receptor and wherein the ligand binds to the cell surface receptor with a binding strength of greater than 500 pN. 
     
     
         5 . The nanoparticle probe of  claim 1 , wherein the associative moiety comprises one or more of oligonucleotide, RGD, sialyl Lewis X, scFv, and/or sdAb. 
     
     
         6 . The nanoparticle probe of  claim 1 , wherein the slip bond comprises one or more of a hyaluronan targeting motif, chondroitin sulfate targeting motif, dermatan sulfate targeting motif, heparan sulfate targeting motif, other lectins or glycocalyx surface targeting motifs, a low affinity antibody, and/or combinations of the foregoing. 
     
     
         7 . The nanoparticle probe of  claim 1 , wherein the nanoparticle base structure comprises a DNA and/or RNA origami, gold nanoparticle, an iron-oxide nanoparticle, poly(amidoamine) (PAMAM) dendrimers, colloidal gold, TNF-bound colloidal gold, albumin, dendrimeric poly(l-lysine), dendrimeric polypropylenimine (PPI), Denkewalter-type PLL dendrimer, Tomalia-type PAMAM dendrimer, hydroxylated PAMAM dendrimer, Hult-type poly(ester) (bis-MPA) dendrimer, Majoral/Caminadetype phosphorous-based dendrimer, Simanek-type triazine based dendrimer, Jayaraman/Jain-type poly(propyletherimine) (PETIM) dendrimer, PEG-PLL, PEG-PAMAM, PETIM-DG, PEG-PPI, peptide dendrimer conjugate, polystyrene latex particles, or combinations thereof. 
     
     
         8 . A method of diagnosing dysfunctional tissue in a patient comprising:
 administering the nanoparticle probe of  claim 1  to the patient; and   detecting the nanoparticle probe in the patient.   
     
     
         9 . The method of  claim 8 , wherein the nanoparticle probe comprises:
 a nanoparticle base structure; and   a slip bond moiety configured to reversibly bind to a glycocalyx of a cell;   a tether functionalized to the nanoparticle base structure and to an associative moiety configured to bind to a cell surface protein of the cell;   wherein the associative moiety preferentially binds to the cell surface protein of the cell based on the thickness of a glycocalyx layer of the cell.   
     
     
         10 . The method of  claim 8 , wherein the dysfunctional tissue of the patient is a cancer tissue. 
     
     
         11 . The method of  claim 8 , wherein the dysfunctional tissue of the patient is caused at least in part by a disease state of the patient. 
     
     
         12 . The method of  claim 9 , wherein the disease state is type-2 diabetes. 
     
     
         13 . The method of  claim 9 , wherein the disease state is hypertension. 
     
     
         14 . The method of  claim 9 , wherein the disease state is chronic kidney disease. 
     
     
         15 . A method of preparing a nanoparticle probe, comprising:
 coupling a tether to a nanoparticle base structure;   coupling a associative moiety to the tether; and   coupling a slip bond moiety to the nanoparticle base structure.