Synthetically functionalized living cells for targeted drug delivery
Uniform, functional polymer patches can be attached to a fraction of the surface area of living individual cells. These surface-modified cells can cross the blood-brain barrier while remaining viable after attachment of the functional patch. Functional payloads carried by the patch can include a drug. The patch can include one or more polyelectrolyte multilayers (PEMs).
1. A composition for targeted drug delivery comprising:
a cell capable of crossing a blood-brain barrier; and
a cell backpack adhered outside the cell to form a cell backpack conjugate, the cell backpack including a polymer patch including a drug, the polymer patch associated with a fractional portion of the cell surface;
wherein the polymer patch includes:
a cytophilic layer having a specific affinity for the cell surface and being substantially in contact with the cell surface;
an exposed layer; and
one or more functional layers intermediate to the cytophilic layer and the exposed layer, wherein the functional layer contains the drug and includes a magnetic region, wherein the functional layer includes a polyelectrolyte multilayer; and
a targeting ligand that is a peptide, an antibody, or an aptamer that helps direct macrophages to the brain, wherein the targeting ligand decorates the cell backpack conjugate resulting in a composition that can deliver a pharmaceutical across a blood-brain barrier.
2. The composition of claim 1 , wherein the cell is a neutrophil, a monocyte, a macrophage, a mast cell, a dendritic cell, or a mesenchymal stem cell.
3. The composition of claim 1 , wherein the cell is a macrophage.
4. The composition of claim 1 , wherein the drug is an enzyme.
5. The composition of claim 4 , wherein the enzyme is catalase.
6. The composition of claim 1 , wherein the drug maintains its activity after crossing the blood-brain barrier.
7. The composition of claim 1 , wherein the cytophilic layer includes hyaluronic acid, chitosan, biotin, an antibody, or an adhesive peptide.
8. The composition of claim 1 , wherein the cytophilic layer includes a polyelectrolyte multilayer.
9. The composition of claim 1 , wherein the exposed layer includes a polyelectrolyte multilayer.
10. The composition of claim 1 , wherein the polyelectrolyte multilayer includes poly(allylamine hydrochloride) (PAH).
11. The composition of claim 1 , further comprising a magnetic layer between the functional layer and the exposed layer.
12. The composition of claim 1 , wherein the polymer patch has lateral dimensions in the range of 1 μm to 250 μm and a thickness in the range of 50 nm to 1 μm.