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 comprising a compound of Formula I:
wherein the following portion of the structure
is a poly(ethylene oxide) (PEO), wherein z is an integer such that the PEO is about 2 kD to about 10 kD in size;
wherein R′ and R″ are each CH 3 ;
wherein R′″ is an endgroup resulting from a polymerization reaction;
wherein R is NR 1 R 2 , wherein R 1 and R 2 are each independently an alkyl group and R 1 and R 2 together have 5 to 10 carbons, or wherein R 1 and R 2 join to form a ring having 5 to 10 carbons;
wherein L is a fluorescent label or a near-infrared label;
wherein x is about 20 to about 200;
wherein y is about 1 to about 6;
wherein n is about 1 to about 4;
wherein m is about 1 to about 4; and
wherein the following portion of the structure:
may be arranged in any order; wherein the block copolymer provides a micelle that has a pH transition range of less than about 0.3 pH unit and a signal response of at least about 10.
2. The block copolymer of claim 1 , wherein the poly(ethylene oxide) (PEO) is about 4 kD to about 6 kD in size.
3. The block copolymer of claim 1 , wherein the poly(ethylene oxide) (PEO) is about 5 kD in size.
4. The block copolymer of claim 1 , wherein R 1 and R 2 are each independently a straight or a branched alkyl.
5. The block copolymer of claim 1 , wherein R 1 and R 2 are each independently propyl or butyl.
6. The block copolymer of claim 1 , wherein R 1 and R 2 join to form a ring having —(CH 2 ) 5 — or —(CH 2 ) 6 —.
7. The block copolymer of claim 1 , wherein the fluorescent label is tetramethyl rhodamine (TMR).
8. The block copolymer of claim 1 , wherein the near-infrared (NIR) label is a cypate or a cypate analog.
9. The block copolymer of claim 1 , wherein x is about 40 to about 100 in total.
10. The block copolymer of claim 1 , wherein y is about 3.
11. The block copolymer of claim 1 , wherein n is about 2.
12. The block copolymer of claim 1 , wherein m is about 2.
13. The block copolymer of claim 1 , wherein the block copolymer is
14. The block copolymer of claim 1 , wherein R′″ is Br, thiolate, or thioester.
15. A composition comprising a pH-sensitive micelle formed from a block copolymer comprising the structure of Formula I:
wherein the following portion of the structure
is a poly(ethylene oxide) (PEO), wherein z is an integer such that the PEO is about 2 kD to about 10 kD in size;
wherein R′ and R″ are each —CH 3 ;
wherein R′″ is an endgroup resulting from a polymerization reaction;
wherein R is —NR 1 R 2 , wherein R 1 and R 2 are each independently an alkyl group and R 1 and R 2 together have 5 to 10 carbons, or wherein R 1 and R 2 join to form a ring having 5 to 10 carbons;
wherein L is a fluorescent label or a near-infrared label;
wherein x is about 20 to about 200;
wherein y is about 1 to about 6;
wherein n is about 1 to about 4;
wherein m is about 1 to about 4;
wherein the following portion of the structure:
may be arranged in any order; and
a carrier; wherein the micelle has a pH transition range of less than about 0.3 pH unit and a signal response of at least about 10.
16. A method of imaging a tumor in an individual in need thereof, comprising (a) administering to the individual a composition comprising a pH-sensitive micelle formed from a block copolymer comprising the structure of Formula I:
wherein the following portion of the structure
is a poly(ethylene oxide) (PEO), wherein z is an integer such that the PEO is about 2 kD to about 10 kD in size;
wherein R′ and R″ are each —CH 3 ;
wherein R′″ is an endgroup resulting from a polymerization reaction;
wherein R is —NR 1 R 2 , wherein R 1 and R 2 are each independently an alkyl group and R 1
and R 2 together have 5 to 10 carbons, or wherein R 1 and R 2 join to form a ring having 5 to 10 carbons;
wherein L is a fluorescent label or a near-infrared label;
wherein x is about 20 to about 200;
wherein y is about 1 to about 6;
wherein n is about 1 to about 4;
wherein m is about 1 to about 4;
wherein the following portion of the structure:
may be arranged in any order; wherein the micelle has a pH transition range of less than about 0.3 pH unit and a signal response of at least about 10; and
(b) measuring emission level of the fluorescent label or a near-infrared label.