Polymer-grafted nanobins

Abstract

Provided herein are small unilaminar vesicles with surface-displayed polymer moieties, and methods of use and manufacture thereof. In particular, provided herein are polymer-grafted nanobins, and methods of drug delivery therewith.

1 . A composition comprising a polymer-grafted nanobin (PGN), wherein said PGN comprises a small unilaminer vesicle comprising a phospholipid-based bilayer with surface-exposed polymers extending therefrom. 
     
     
         2 . The composition of  claim 1 , wherein said small unilaminer vesicle is between 15 and 50 nm in diameter. 
     
     
         3 . (canceled) 
     
     
         4 . The composition of  claim 1 , wherein said small unilaminer vesicle comprises 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), Dipalmitoylphosphatidylcholine (DPPC), and/or 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC). 
     
     
         5 . The composition of  claim 1 , wherein said surface-exposed polymers comprise poly(acrylic acid) extending from cholesterol-terminated poly(acrylic acid) (Chol-PAA), wherein the cholesterol portion of the Chol-PAA is inserted into the bilayer. 
     
     
         6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein said PGN further comprises a molecular payload encapsulated within said small unilaminar vesicle. 
     
     
         8 . The composition of  claim 7 , wherein said molecular payload comprises a small molecule, peptide, or nucleic acid. 
     
     
         9 . The composition of  claim 7 , wherein, said PGN releases less than 20% of said payload over the course of one month at normal physiologic conditions, and said PGN releases at least 50% of said payload over the course of less than one hour at a pH between 4.0 and 6.0. 
     
     
         10 . (canceled) 
     
     
         11 . The composition of  claim 1 , wherein said surface-exposed polymers are not cross-linked. 
     
     
         12 . The composition of  claim 1 , comprising a polymer-grafted nanobin (PGN), wherein said PGN comprises a small phospholipid-based unilaminer vesicle (SUV) comprising cholesterol-terminated poly(acrylic acid) groups (Chol-PAA), wherein said Chol-PAA is oriented such that said poly(acrylic acid) is surface exposed and extends from said SUV into the surrounding environment, wherein said SUV encompasses a molecular payload comprising one or more peptides, nucleic acids, and/or small molecules. 
     
     
         13 . A method of drug delivery to a low-pH microenvironment within a subject comprising:
 (a) administering a polymer-grafted nanobin (PGN) of  claim 12  to said subject; and   (b) allowing said PGN to migrate from physiologic conditions to an acidic microenvironment.   
     
     
         14 . The method of  claim 13 , wherein the PGN is administered locally at or near the acidic microenvironment. 
     
     
         15 . The method of  claim 13 , wherein the PGN is administered systemically. 
     
     
         16 . The method of  claim 13 , wherein said acidic microenvironment is a tumor. 
     
     
         17 . The method of  claim 16 , wherein said therapeutic agent is a chemotherapeutic. 
     
     
         18 . The method of  claim 16 , wherein said payload is a nucleic acid-based therapy. 
     
     
         19 . The method of  claim 13 , wherein said PGN releases less than 20% of said payload over the course of one month at normal physiologic conditions and releases at least 50% of said payload over the course of less than one hour at a pH between 4.0 and 6.0. 
     
     
         20 . The method of  claim 13 , wherein the PGN is co-administered with an additional therapeutic agent. 
     
     
         21 . The method of  claim 16 , further comprising a step of surgically removing the tumor. 
     
     
         21 . (canceled) 
     
     
         22 .- 29 . (canceled) 
     
     
         30 . A method of preparing a polymer-grafted nanobin (PGN) comprising:
 (a) preparing a lipid mixture by dissolving selected lipids in an organic solvent;   (b) hydrating the product of step (a) with an aqueous hydration solvent to form liposomes;   (c) sizing the liposomes to yield small unilaminar vesicles (SUVs); and   (d) incubating the SUVs with lipid-anchored polymer to generate PGNs with surface exposed polymer.   
     
     
         31 .- 46 . (canceled) 
     
     
         47 . The method of  claim 21 , wherein the administration step is performed after surgical removal of the tumor.