Nanoparticle probes and methods of making and use thereof
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.
1. A nanoparticle probe comprising:
a nanoparticle base structure; and
a slip bond moiety comprising a ligand for a glycocalyx of a cell, the slip bond being configured to reversibly bind to the glycocalyx of a cell;
a tether functionalized to the nanoparticle base structure and to an associative moiety comprising a ligand for a cell surface protein, a receptor, or a cell surface biomarker, wherein the associative moiety;
wherein the associative moiety preferentially binds to the cell surface protein, the receptor, or the 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 has a binding strength to the cell surface protein, the receptor, or the cell surface biomarker of greater than 500 pN.
5. The nanoparticle probe of claim 1 , wherein the associative moiety comprises an oligonucleotide, RGD, or a combination thereof.
6. The nanoparticle probe of claim 1 , wherein the slip bond moiety comprises a hyaluronan targeting motif, chondroitin sulfate targeting motif, dermatan sulfate targeting motif, heparan sulfate targeting motif, other lectins, or combinations thereof.
7. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises a DNA and/or RNA origami.
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 dysfunctional tissue of the patient is a cancer tissue.
10. 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.
11. The method of claim 10 , wherein the disease state is type-2 diabetes.
12. The method of claim 10 , wherein the disease state is hypertension.
13. The method of claim 10 , wherein the disease state is chronic kidney disease.
14. The nanoparticle probe of claim 1 , wherein the associative moiety comprises sialyl Lewis X, scFv, sdAb, or combinations thereof.
15. The nanoparticle probe of claim 1 , wherein the slip bond moiety comprises a low affinity antibody.
16. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises a gold nanoparticle, an iron-oxide nanoparticle, colloidal gold, TNF-bound colloidal gold, or combinations thereof.
17. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises a poly(amidoamine) (PAMAM) dendrimer, dendrimeric poly(l-lysine) (PLL), dendrimeric polypropylenimine (PPI), a Denkewalter-type PLL dendrimer, a Tomalia-type PAMAM dendrimer, a hydroxylated PAMAM dendrimer, a Hult-type poly(ester) (bis-MPA) dendrimer, Majoral/Caminadetype phosphorous-based dendrimer, a Simanek-type triazine based dendrimer, Jayaraman/Jain-type poly(propyletherimine) (PETIM) dendrimer, peptide dendrimer conjugate, or combinations thereof.
18. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises polyethylene glycol (PEG)-PLL, PEG-PAMAM, PETIM-DG, PEG-PPI, polystyrene latex particles, or combinations thereof.
19. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises albumin.