Engineered liposomes as cancer-targeted therapeutics
The disclosure provides liposomes (e.g., cancer-targeting liposomes) with ligands (e.g., EGFR ligands and ICAM-1 ligands) conjugated to liposome surfaces. In some embodiments, the molecular ratio of different ligands complement the relative molecular density (i.e., ratio) of overexpressed protein on the surface of a cell targeted by the liposome (e.g., cancer cell).
1. A liposome comprising:
(i) a lipid bilayer;
(ii) an EGFR antibody conjugated to the liposome surface;
(iii) an ICAM-1 antibody conjugated to the liposome surface; and
(iv) a therapeutic agent encapsulated in the liposome,
wherein the ratio of ICAM-1 antibody to EGFR antibody complements the ratio of ICAM-1 to EGFR protein on the surface of a triple negative breast cancer (TNBC) cell and the ratio is between 1 and 5.
2. The liposome of claim 1 , wherein the lipid bilayer comprises a neutral lipid.
3. The liposome of claim 2 , wherein the neutral lipid is 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).
4. The liposome of claim 1 , wherein the lipid bilayer comprises an anionic lipid.
5. The liposome of claim 1 , wherein the lipid bilayer further comprises a functionalized lipid.
6. The liposome of claim 5 , wherein the functionalized lipid is a lipid-polymer conjugate.
7. The liposome of claim 5 , wherein the functionalized lipid is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000]-COOH (DSPE-PEG-COOH).
8. The liposome of claim 1 , wherein the functionalized lipid is up to 10% of total lipids in the liposome.
9. The liposome of claim 1 , wherein the EGFR ligand or the ICAM-1 ligand is conjugated to the functionalized lipid.
10. The liposome of claim 1 , wherein the lipid bilayer further comprises a pH-responsive lipid.
11. The liposome of claim 10 , wherein the pH-responsive lipid comprises 1,2-dioleoyl-3-dimethylammoniumpropane (DODAP).
12. The liposome of claim 1 , wherein the ratio of ICAM-1 antibody to EGFR antibody is 1.5 or 4.2.
13. The liposome of claim 1 , wherein the therapeutic agent is an anticancer agent.
14. A pharmaceutical composition comprising the liposome of claim 1 .
15. A method of treating triple negative breast cancer (TNBC), the method comprising administering to a subject in need thereof a therapeutically effective amount of the liposome of claim 1 .