Compositions and methods relating to erythrocytes with adhered particles
Provided herein are erythrocytes with polymeric particles (i.e., ‘backpacks’) adhered that provide delivery of payload therapeutic agents to subjects administered these cells.
1 . A composition comprising:
a) an erythrocyte; and
b) more than 20 particles located on the cell surface of the erythrocyte, each particle comprising:
i) poly(lactic-co-glycolic acid) (PLGA); and
ii) at least one therapeutic agent.
2 . The composition of claim 1 , wherein the PLGA comprises ester ends and/or acid ends.
3 . The composition of claim 1 , wherein the at least one therapeutic agent is selected from the group consisting of:
a chemotherapeutic agent; an antigen; a steroid; an immunosuppressant agent; an immunostimulatory agent; a virus; a small molecule; a peptide; a nucleic acid; and a chemokine.
4 . The composition of claim 3 , wherein the at least one chemotherapeutic agent is selected from the group consisting of:
doxorubicin; camptothecin; paclitaxel; docetaxel; 5-fluorouracil; gemcitabine; methotrexate; and a combination of any of the foregoing.
5 . The composition of claim 3 , wherein the at least one therapeutic agent is an antigen.
6 . The composition of claim 1 , wherein the PLGA comprises a L:G ratio with more L than G.
7 . The composition of claim 1 , wherein the PLGA comprises a L:G ratio of about 85:15.
8 . The composition of claim 1 , wherein the PLGA comprises a L:G ratio of about 65:35.
9 . The composition of claim 1 , wherein the PLGA comprises a L:G ratio of about 85:15 and ester ends.
10 . The composition of claim 1 , wherein the PLGA comprises a L:G ratio of about 65:35 and acid ends.
11 . The composition of claim 1 , wherein the at least one therapeutic agent is present at a concentration of at least 100 μg per 3×10 8 erythrocytes.
12 . The composition of claim 1 , wherein the diameter of the particle is from about 100 nm to about 10 μm.
13 . The composition of claim 1 , wherein the particle further comprises one or more cell adhesive molecules.
14 . The composition of claim 13 , wherein the one or more cell adhesive molecules is localized to a region of the particle surface.
15 . The composition of claim 13 , wherein the one or more cell adhesive molecule is selected from the group consisting of:
an antibody reagent that binds specifically to a molecule on a red blood cell; a peptide that binds specifically to a molecule on a red blood cell; a cell adhesive polymer; a cell adhesive polyelectrolyte; and a ligand for a receptor on a red blood cell.
16 . The composition of claim 15 , wherein the one or more cell adhesive polyelectrolytes comprise hyaluronic acid, hyaluronic acid-aldehyde, and/or poly(allylamine) hydrochloride.
17 . The composition of claim 15 , wherein the one or more cell adhesive polymers is a polyphenol or metal-polyphenol network.
18 . A method of delivering a therapeutic agent to a cell in a subject, the method comprising administering to the subject a composition of claim 1 , wherein the therapeutic agent is a chemotherapeutic agent or a chemokine.
19 . A method of treating cancer and/or a tumor in a subject in need thereof, the method comprising administering to the subject a composition of claim 1 .
20 . A method of stimulating an immune response in a subject in need thereof, the method comprising administering to the subject a composition of claim 1 ,
wherein the therapeutic agent is an antigen, an immunostimulatory agent, or a chemokine.
21 . A method of decreasing or suppressing an immune response in a subject in need thereof, the method comprising administering to the subject a composition of claim 1 ,
wherein the therapeutic agent is an immunomodulatory agent or a steroid.