IP Library › Granted Patent US 12,447,215
Granted Patent B2
US 12,447,215 · App. 18/211,938 · Granted Oct 21, 2025

Nanoparticle probes and methods of making and use thereof

Inventor: Paul C. Lee (Columbia, MD)
A61K49/0093G01N33/54346G01N33/587G01N33/6842G01N33/6893G01N2400/40G01N2800/042G01N2800/321G01N2800/347
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,447,215
App. No.
18/211,938
Granted
Oct 21, 2025
Kind
B2
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.

Claims (32)

1. A nanoparticle probe comprising:

a nanoparticle base structure functionalized with a therapeutic agent, wherein the therapeutic agent is a growth factor; and

a slip bond moiety comprising a ligand for a glycocalyx of a cell;

a polymeric tether functionalized to the nanoparticle base structure and to an associative moiety, wherein said associative moiety comprises a ligand for a cell surface protein, a receptor, or a biomarker; and

wherein the associative moiety preferentially binds to the protein, the receptor, and 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 therapeutic agent is vascular endothelial growth factor (VEGF), angiopoietins, fibroblast growth factor (FGF) or combinations thereof.

3. The nanoparticle probe of claim 1 , wherein the associative moiety binds irreversibly.

4. The nanoparticle probe of claim 1 wherein the nanoparticle probe is functionalized with one or more dye or radio opaque agent for visualization.

5. The nanoparticle probe of claim 1 , wherein the associative moiety comprises an oligonucleotide.

6. The nanoparticle probe of claim 1 wherein the tether length is between 20-200 nm.

7. The nanoparticle probe of claim 1 wherein the associative moiety penetrates the glycocalx.

8. 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, and/or combinations of the foregoing.

9. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises poly(amidoamine) (PAMAM) dendrimers, 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, peptide dendrimer conjugate, or combinations thereof.

10. The nanoparticle probe of claim 1 , wherein the nanoparticle probe self-assembles into a nucleation site for bone development.

11. A method of diagnosing a dysfunctional tissue in a patient comprising:

administering the nanoparticle probe of claim 1 to the patient; and

detecting the nanoparticle probe in the patient.

12. The method of claim 11 , wherein the dysfunctional tissue of the patient is a bone, heart, kidney, liver, lung, intestine or pancreatic tissue.

13. The method of claim 11 , wherein the dysfunctional tissue of the patient is bone with osteoporosis.

14. The method of claim 11 , wherein the patient is in need of a bone graft.

15. The method of claim 11 , wherein an increase in bone density is detected.

16. A method of treating a disease in a patient comprising:

administering the nanoprobe of claim 1 to the patient; and

detecting a change in tissue density in the patient.

17. The method of claim 16 wherein an increase in vasculature, circulation, bone density and/or extra cellular matrix deposition is detected.

18. The nanoparticle probe of claim 1 , wherein the associative moiety comprises sialyl Lewis X.

19. The nanoparticle probe of claim 1 , wherein the associative moiety comprises one or more of RGD, scFv, or sdAb.

20. The nanoparticle probe of claim 1 , wherein the slip bond moiety comprises a lectin.

21. The nanoparticle probe of claim 1 , wherein the slip bond moiety comprises an antibody.

22. The nanoparticle probe of claim 1 , wherein the nanoparticle base structure comprises DNA origami or RNA origami.

23. 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.

24. 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.

Continuity (6)
Continuation 17465571 · Sep 2, 2021
Continuation 16669059 · Oct 30, 2019
Continuation 15680016 · Aug 17, 2017
Continuation In Part 15461035 · Mar 16, 2017
Provisional Application 62309751 · Mar 17, 2016
Related Publication 20240100196A1 · Mar 28, 2024
References Cited (32)
US 9040310B2 · Ashworth-Sharpe · 2015 [cited by examiner]
US 9044385B2 · Pacetti et al. · 2015 [cited by applicant]
US 9072665B2 · Ludwig et al. · 2015 [cited by applicant]
US 10507252B2 · Lee · 2019 [cited by applicant]
US 10507253B2 · Lee · 2019 [cited by applicant]
US 20040067544A1 · Vogel et al. · 2004 [cited by applicant]
US 20050180945A1 · Chaikof et al. · 2005 [cited by applicant]
US 20060251580A1 · Keppler et al. · 2006 [cited by applicant]
US 20090325259A1 · Vogel et al. · 2009 [cited by applicant]
US 20100028902A1 · Brown et al. · 2010 [cited by applicant]
US 20100104506A1 · Ludwig et al. · 2010 [cited by applicant]
US 20100304424A1 · Vink et al. · 2010 [cited by applicant]
US 20150023875A1 · Farokhzad et al. · 2015 [cited by applicant]
US 20150140598A1 · Daniels et al. · 2015 [cited by applicant]
US 20150160214A1 · Auton · 2015 [cited by applicant]
US 20170269095A1 · Lee · 2017 [cited by applicant]
Andersen E, Nielsen M., “DNA origami design of 3D nanostructures.” Protocol Exchange. 2009. doi: 10.1038/nprot.2009.75. [cited by applicant]
Becker BF, Chappell D, Bruegger D, Annecke T, Jacob M. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovasc Res. 2010;87(2):300-10. doi: 10.1093/cvr/cvq137. PubMed… [cited by applicant]
Calderon AJ, Baig M, Pichette B, Muzykantov V, Muro S, Eckmann DM. Effect of Glycocalyx on Drug Delivery Carriers Targeted to Endothelial Cells. Int J Transp Phenom. 2011;12(1-2):63-75. PubMed PMID: 22679359; PMCID: PMC… [cited by applicant]
Farr, et al., “Imaging Early Endothelial Inflammation Following Stroke by Core Shell Silica Superparamagnetic Glyconanoparticles That Target Selectin,” American Chemical Society Publications, Nano Letters, 2014, 14, pp.… [cited by applicant]
Graf F LC, Janssen B, Ingber DE, Shih WM. Controlling cellular uptake of nanoparticles by designing their shape using DNA origami. Doctoral Dissertation, Harvard University. 2012. [cited by applicant]
Hartman, et al., “Supported lipid bilayers as dynamic platforms for tethered particles,” Royal Society of Chemistry, Nanoscale, 2015, vol. 7, pp. 66-76. [cited by applicant]
Kannan RM, Nance E, Kannan S, Tomalia DA. Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J Intern Med. 2014;276(6):579-617. doi: 10.1111/joim.12280. PubMed PMID: 2499… [cited by applicant]
Liu, et al., “Multivalent Binding of Nanocarrier to Endothelial Cells under Shear Flow,” Biophysical Journal, Jul. 2011, vol. 101, pp. 319-326. [cited by applicant]
Marchi AN, Saaem I, Vogen BN, Brown S, LaBean TH. Toward larger DNA origami. Nano Lett. 2014;14(10):5740-7. doi: 10.1021/nl502626s. PubMed PMID: 25179827. [cited by applicant]
Onyskiw et al., “Effect of PEGylation on Ligand-Based Targeting of Drug Carriers to the Vascular Wall in Blood Flow,” American Chemical Society Publications, Langmuir, 2013, 29, pp. 11127-11134. [cited by applicant]
Palcic MM, Li H, Zanini D, Bhella RS, Roy R. Chemoenzymatic synthesis of dendritic sialyl Lewis(x). Carbohydr Res. 1997;305(3-4):433-42. PubMed PMID: 9648262. [cited by applicant]
Rajendran A, Endo M, Sugiyama H. DNA origami: synthesis and self-assembly. Curr Protoc Nucleic Acid Chem. 2012;Chapter 12:Unit 12 9 1-8. doi: 10.1002/0471142700.nc1209s48. PubMed PMID: 22395964. [cited by applicant]
Shaw A, Benson E, Hogberg B. Purification of functionalized DNA origami nanostructures. ACS Nano. 2015;9(5):4968-75. doi: 10.1021/nn507035g. PubMed PMID: 25965916. [cited by applicant]
Slooter MD, Bierau K, Chan AB, Lowik CW. Near infrared fluorescence imaging for early detection, monitoring and improved intervention of diseases involving the joint. Connect Tissue Res. 2015;56(2):153-60. doi: 10.3109/… [cited by applicant]
Türkcan, et al., “Receptor Displacement in the Cell Membrane by Hydrodynamic Force Amplification through Nanoparticles,” Biophysical Journal, Jul. 2013, vol. 105, pp. 116-126. [cited by applicant]
Van Kasteren et al., “Glyconanoparticles allow pre-symptomatic in vivo imaging of brain disease,” PNAS, Jan. 2009, vol. 106, No. 1, pp. 18-23. [cited by applicant]