Targeted delivery system, system components, and methods
A method for targeted delivery of cargo to a target locus in a subject and components of the system. Generally, the method includes administering to the subject a cell that has an artificial saccharide-derived target presented on the surface of the cell, allowing the cell to localize to a target locus in the subject, then administering to the subject an agent that specifically binds to the artificial target. In some embodiments, the agent can include a therapeutic compound. In some embodiments, the agent can include a detectable label. In some of these embodiments, that method can further include detecting the detectable label.
1. A therapeutic delivery system comprising:
a glycoengineered, undifferentiated mesenchymal stem cell capable of selectively accumulating in a tumor, the glycoengineered, undifferentiated mesenchymal stem cell comprising an artificial surface saccharide, the artificial surface saccharide comprising a reactive functional group; and
a therapeutic agent comprising a functional group that is reactive with the reactive functional group;
with the proviso that the glycoengineered stem cell does not comprise a targeting antibody.
2. The therapeutic delivery system of claim 1 , wherein the reactive functional group comprises an azide functional group.
3. The therapeutic delivery system of claim 1 , wherein the therapeutic agent is bound to the glycoengineered mesenchymal stem cell by reaction of the reactive functional group with the therapeutic agent functional group.
4. The therapeutic delivery system of claim 3 , wherein the reactive functional group comprises an azide functional group and the therapeutic agent functional group comprises a group that is reactive with the azide functional group.
5. The therapeutic delivery system of claim 4 , wherein the therapeutic agent functional group comprises dibenzyl cyclooctyne.
6. The therapeutic delivery system of claim 1 , further comprising a detectable label.
7. The therapeutic delivery system of claim 6 , wherein the detectable label is bound to:
the therapeutic agent, or
a second artificial surface saccharide.
8. The therapeutic delivery system of claim 1 , further comprising a therapeutic agent loaded into the glycoengineered mesenchymal stem cell.
9. A method comprising:
administering to a subject the glycoengineered mesenchymal stem cell of the therapeutic delivery system of claim 1 ; and
administering to the subject the therapeutic agent of the therapeutic delivery system of claim 1 .
10. The method of claim 9 , wherein the glycoengineered mesenchymal stem cell further comprises a detectable label.
11. The method of claim 10 , further comprising detecting the detectable label.
12. The method of claim 9 , further comprising allowing the cell to localize to a target locus in the subject.