Bispecific intracellular delivery vehicles

1. A composition for delivering a therapeutic or diagnostic agent to a cell, comprising:

a bispecific affinity reagent and a pH-responsive, membrane destabilizing polymer comprising a plurality of pendant linking groups,

wherein the bispecific affinity reagent is a bispecific scFv.

2. The composition of claim 1 , wherein the bispecific affinity reagent is linked to an end group of the polymer.

3. The composition of claim 1 , wherein the bispecific affinity reagent is linked to one of the plurality of pendant linking groups.

4. The composition of claim 1 , wherein the bispecific affinity reagent is cleavably linked to the polymer.

5. The composition of claim 1 , wherein the bispecific affinity reagent is cleavably linked to the polymer through a disulfide bond.

6. The composition of claim 1 , wherein the bispecific affinity reagent is cleavably linked to the polymer through a pH-sensitive bond.

7. The composition of claim 6 , wherein the pH-sensitive bond is a hydrazone or acetal.

8. The composition of claim 1 , wherein the second affinity reagent is a peptide or ligand for the asialoglycoprotein receptor.

9. The composition of claim 1 , wherein the pH-responsive, membrane destabilizing polymer is a copolymer.

10. The composition of claim 1 , wherein the pH-responsive, membrane destabilizing polymer is a block copolymer.

11. The composition of claim 1 , wherein the pH-responsive, membrane destabilizing polymer is a diblock copolymer.

12. The composition of claim 1 , wherein the pH-responsive, membrane destabilizing polymer comprises alkyl acrylate monomers, alkyl (alkyl)acrylate monomers, or a combination thereof.

13. The composition of claim 12 , wherein the pH-responsive, membrane destabilizing polymer comprises propyl acrylic acid monomers.

14. The composition of claim 12 , wherein the pH-responsive, membrane destabilizing polymer comprises butyl methacrylate monomers.

15. The composition of claim 12 , wherein the pH-responsive, membrane destabilizing polymer comprises N,N-dimethylaminoethylmethacrylate monomers.

16. The composition of claim 12 , wherein the pH-responsive, membrane destabilizing polymer comprises propyl acrylic acid monomers, N,N-dimethylaminoethylmethacrylate monomers, and butyl methacrylate monomers.

17. The composition of claim 1 , wherein the pH-responsive, membrane destabilizing polymer comprises a diblock copolymer wherein one block comprises propyl acrylic acid monomers, N,N-dimethylaminoethylmethacrylate monomers and butyl methacrylate monomers.

18. The composition of claim 1 , wherein the pH-responsive, membrane destabilizing polymer is a polymer of Formula (4):

[PEGMA] v -[B p -/-P q -/-D r ] w   (4),

wherein

B is butyl methacrylate residue; P is propyl acrylic acid residue; D is dimethylaminoethyl methacrylate residue; PEGMA is polyethyleneglycol methacrylate residue with 1-20 ethylene oxide units, 4-5 ethylene oxide units, or 7-8 ethylene oxide units;

p is 0.1 to 0.9;

q is 0.1 to 0.9;

r is 0 to 0.8, wherein p+q+r=1;

v is 1 to 25 kDa; and

w is 1 to 50 kDa.

19. The composition of claim 1 , wherein the pH-responsive, membrane destabilizing polymer is a polymer of Formula (9):

[PEGMA m -/-PDSM n ] v -[B p -/-P q -/-D r ] w   (9),

wherein

B is butyl methacrylate residue; P is propyl acrylic acid residue; D is dimethylaminoethyl methacrylate residue; PDSM is pyridyl disulfide methacrylate residue, PEGMA is polyethyleneglycol methacrylate residue with 1-20 ethylene oxide units, 4-5 ethylene oxide units, or 7-8 ethylene oxide units;

m is 0 to less than 1.0;

n is greater than 0 to 1.0 wherein

m+n=1;

p is 0.1 to 0.9;

q is 0.1 to 0.9;

r is 0 to 0.8 wherein p+q+r=1;

v is 1 to 25 kDa; and

w is 1 to 50 kDa.