Living cells engineered with polyphenol-functionalized biologically active nanocomplexes
Described herein are functionalizing nanocomplexes comprising one or more polyphenol molecules; and one or more biomolecules. Further described herein are functionalized cells comprising one or more of the nanocomplexes. In some embodiments, the biomolecules can be therapeutic agents and the functionalized cells can be administered to patients to provide improved delivery (e.g., dosing and specificity) of the therapeutic agent.
1 . A mammalian hematopoietic cell comprising at least one nanocomplex comprising:
a) one or more polyphenol molecules; and
b) one or more biomolecules or one or more active agents:
wherein the at least one nanocomplex is adhered to the surface of the mammalian hematopoietic cell.
2 . The cell of claim 1 , wherein the mammalian hematopoietic cell is an erythrocyte, T cell, monocyte, macrophage, neutrophil or natural killer cell.
3 . The cell of claim 1 , wherein the at least one nanocomplex collectively comprises 10 to 1 trillion biomolecules or active agents.
4 . A method comprising:
a) combining i) one or more polyphenol molecules and ii) one or more biomolecules or one or more active agents; and
b) contacting a mammalian hematopoietic cell with the combination resulting from step a; whereby a nanocomplex forms and adheres to the surface of the mammalian hematopoietic cell.
5 . A method of administering a biomolecule and/or active agent to a patient in need of treatment with the biomolecule and/or active agent, the method comprising administering a mammalian hematopoietic cell of claim 1 to the patient.
6 . The method of claim 5 , wherein the mammalian hematopoietic cell is autologous to the patient.
7 . The mammalian hematopoietic cell of claim 1 , wherein the one or more polyphenols collectively comprise at least one galloyl moiety and/or at least one catechol moiety.
8 . The mammalian hematopoietic cell of claim 1 , wherein the polyphenol is tannic acid.
9 . The mammalian hematopoietic cell of claim 1 , wherein the stoichiometric ratio of polyphenol molecules to biomolecules is 570 or less relative polyphenol.
10 . The mammalian hematopoietic cell of claim 1 , wherein the at least one biomolecule or at least one active agent is a nucleic acid, protein, a viral particle, a viral vector, alkaloid, polysaccharide, anthocyanin, lipid, antiviral drug, antibiotic, chemotherapeutic, or combination thereof.
11 . The mammalian hematopoietic cell of claim 1 , wherein at least one biomolecule or at least one active agent is an antibody specific for an immune checkpoint protein.
12 . The mammalian hematopoietic cell of claim 1 , wherein at least one biomolecule or at least one active agent is a viral particle or viral vector.
13 . The mammalian hematopoietic cell of claim 12 , wherein the viral particle or viral vector is an adeno-associated virus vector.
14 . The mammalian hematopoietic cell of claim 13 , wherein the adeno-associated virus vector is AAV9.