SURFACED MODIFICATION OF NALNF4 NANOPARTICLES WITH BISPHOSPHONATE DERIVATIVES FOR MASS CYTOMETRY APPLICATIONS
Described herein are nanoparticles comprising NaLnF4, wherein Ln includes all non-radioactive lanthanide elements, or NaYF4, and methods of making and using the same. The nanoparticles may optionally be modified with PEG or zwitterionic polymers containing a bisphosphonate end group, wherein the bisphosphonate end group optionally comprises an aminohexyl group. As described herein. NaLnF4 or NaYF4 nanoparticles may be used as high-sensitivity reagents for mass cytometry.
1 . A nanoparticle, the nanoparticle comprising:
NaLnF 4 , wherein Ln includes all non-radioactive lanthanide elements, or NaYF 4 .
2 . The nanoparticle of claim 1 , further comprising a dopant.
3 . The nanoparticle of claim 2 , wherein the dopant comprises Yb and Er.
4 . The nanoparticle of any one of claims 1 to 3 , wherein the nanoparticle is modified with PEG or zwitterionic polymers containing a bisphosphonate end group.
5 . The nanoparticle of claim 4 , wherein the nanoparticle is modified with the zwitterionic polymer, and the bisphosphonate end group comprises an aminohexyl bisphosphonate.
6 . The nanoparticle of claim 5 , wherein the aminohexyl bisphosphonate comprises Neridronate.
7 . The nanoparticle of claim 5 , wherein the aminohexyl bisphosphonate comprises alendronate.
8 . The nanoparticle of claim 7 , wherein the alendronate is conjugated to poly(sulfobetaine methacrylate) (PSBMA) at one end.
9 . The nanoparticle of claim 8 , wherein the nanoparticle is further modified with alendronate conjugated to PEG at one end.
10 . The nanoparticle of any of claims 4 to 6 , wherein the nanoparticle is modified with poly(sulfobetaine methacrylate) (PSBMA).
11 . The nanoparticle of claim 10 , wherein the Neridronate is conjugated to one end (PSBMA-Ner).
12 . The nanoparticle of claim 10 or 11 , wherein the nanoparticle is further modified with PEG.
13 . The nanoparticle of claim 12 , wherein the PEG is PEG 2000 or PEG 5000 .
14 . The nanoparticle of claim 12 or 13 , wherein an azide functional group is conjugated to the PEG.
15 . The nanoparticle of any one of claims 12 to 13 , wherein the PEG is conjugated to Neridronate (PEG-Ner).
16 . The nanoparticle of claim 1 , wherein the nanoparticle is modified with PSBMA conjugated to Neridronate at one end (PSBMA-Ner) and with PEG conjugated to Neridronate at one end (PEG-Ner).
17 . The nanoparticle of claim 16 , wherein the PSBMA-Ner is 30% to 40%, 40% to 50%, or 50% to 60% of the total PSBMA-Ner and PEG-Ner modifications.
18 . The nanoparticle of any one of claims 1 to 17 , wherein the diameter of the nanoparticle as measured by transmission electron microscopy is in a range from 10 nm to 50 nm.
19 . The nanoparticle of any of claims 1 to 18 , wherein the nanoparticle comprises at least 10 5 Ln ions.
20 . The nanoparticle of any one of claims 1 to 19 , wherein the nanoparticle is attached to an antibody or other bioaffinity agent.
21 . A method of analyzing a cell, the method comprising introducing the cell to the nanoparticle of any one of claims 1 to 20 .
22 . A mass cytometry system, the mass cytometry system comprising the nanoparticle of any one of claims 1 to 19 .
23 . A mixture of nanoparticles, the mixture comprising a plurality of nanoparticles, each nanoparticle being a nanoparticle of any one of claims 1 to 19 .
24 . The mixture of claim 23 , wherein the plurality of nanoparticles comprises at least 10, 100, 1,000, 10,000, 100,000, 1,000,000, or 10,000,000 nanoparticles.