Nanoparticle probes and methods of making and use thereof
View Patent ↗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 binding motif for a glycocalyx and having a binding strength to the glycocalyx of less than about 100 pN, wherein the slip bond moiety is configured to reversibly bind to the glycocalyx of a cell;
a polymeric tether functionalized to the nanoparticle base structure and to an associative moiety comprising a cell surface binding moiety configured to bind to a one or more of a cell surface protein, receptor, and/or biomarker of the cell with a binding strength of larger than 100 pN;
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 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.
3. The nanoparticle probe of claim 1 , wherein the associative moiety comprises an oligonucleotide.
4. The nanoparticle probe of claim 1 , wherein the slip bond moiety comprises one or more of a hyaluronan targeting motif, chondroitin sulfate targeting motif, dermatan sulfate targeting motif, heparan sulfate targeting motif, and/or combinations of the foregoing.
5. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises a poly(amidoamine) (PAMAM) dendrimers, 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, a peptide dendrimer conjugate, or combinations thereof.
6. 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.
7. The nanoparticle probe of claim 1 , wherein the associative moiety comprises sialyl Lewis X.
8. The nanoparticle probe of claim 1 , wherein the associative moiety comprises one or more of RGD, scFv, or sdAb.
9. The nanoparticle probe of claim 1 , wherein the slip bond moiety comprises a lectin.
10. The nanoparticle probe of claim 1 , wherein the slip bond moiety comprises an antibody.
11. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises DNA origami.
12. 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.
13. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises albumin, polystyrene latex particles, PEG-PLL, PEG-PAMAM, PETIM-DG, PEG-PPI, or combinations thereof.