Block copolymer and micelle compositions and methods of use thereof
Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises wherein R′ is —H or —CH 3 , wherein R is —NR 1 R 2 , wherein R 1 and R 2 are alkyl groups, wherein R 1 and R 2 are the same or different, wherein R 1 and R 2 together have from 5 to 16 carbons, wherein R 1 and R 2 may optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.
1. A block copolymer capable of forming a pH-sensitive micelle comprising a compound of Formula (I):
wherein R is —NR 1 R 2 , wherein R 1 and R 2 are straight alkyl groups, wherein R 1 and R 2 are the same or different, wherein R 1 and R 2 together have from 5 to 16 carbons, and wherein R 1 and R 2 may optionally join to form a ring;
L is a labelling moiety;
R′ is —H or —CH3;
n is 1 to about 10;
m is 1 to about 10;
x is about 20 to about 200 in total;
y is 0 to about 6;
wherein z is such that the PEO is about 2 kD to about 20 kD in size;
wherein R′″ is any suitable moiety; and
wherein the following portion of the structure:
may be arranged in any order.
2. The block copolymer of claim 1 , wherein the micelles have a pH transition range of less than about 1 pH unit.
3. The block copolymer of claim 1 , wherein n is 2 and R 1 and R 2 is n-Bu.
4. The block copolymer of claim 3 , wherein the micelles have a pH transition value of about 5.4.
5. The block copolymer of claim 1 , wherein n is 2 and R 1 and R 2 join to form a ring having —(CH 2 ) 5 —.
6. The block copolymer of claim 5 , wherein the micelles have a pH transition value of about 7.2.
7. The block copolymer of claim 1 , wherein n is 2 and R 1 and R 2 join to form a ring having —(CH 2 ) 6 —.
8. The block copolymer of claim 7 , wherein the micelles have a pH transition value about 6.8.
9. The block copolymer of claim 1 , wherein the block copolymer has a polydispersity index of less than 1.2.
10. The block copolymer of claim 1 , wherein the block copolymer has a polydispersity index of less than 1.1.
11. The block copolymer of claim 1 , wherein the micelles have a size of about 10 to about 200 nm.
12. The block copolymer of claim 1 , wherein the micelles have a size of about 20 to about 100 nm.
13. The block copolymer of claim 1 , wherein the micelles have a size of about 30 to about 50 nm.
14. The block copolymer of claim 1 , wherein L is a fluorescent label.
15. The block copolymer of claim 1 , wherein the NIR label is cypate or a cypate analog.