Targeting trastuzumab-resistant her2+ breast cancer with a her3-targeting nanoparticle

Abstract

Disclosed herein are methods of treating cancer in a patient, the method comprising identifying a patient who is resistant to treatment with an anti-HER2 therapy; and administering to the patient a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; a nucleic acid molecule bound to the polypeptide sequence via electrostatic interactions; and a chemical agent non-covalently linked to the nucleic acid sequence. Also disclosed are methods of inducing apoptosis in an anti-HER2 therapy resistant HER2+ breast cancer cell, the method comprising contacting the anti-HER2 therapy resistant HER2+ breast cancer cell with the drug delivery molecule. Further disclosed herein are methods of treating cancer in a patient, the method comprising identifying a patient who is resistant to anti-HER2 therapy; and administering to the patient a therapeutically effective amount of a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; and a sulfonated corrole molecule bound to the polypeptide sequence. Finally disclosed herein are methods of inducing apoptosis in an anti-HER2 therapy resistant HER2+ breast cancer cell, the method comprising contacting the anti-HER2 therapy resistant HER2+ breast cancer cell with a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; and a sulfonated corrole molecule bound to the polypeptide sequence.

1 - 35 . (canceled) 
     
     
         36 . A method of treating a triple-negative breast cancer in a patient, comprising:
 administering to the patient a therapeutically effective amount of a drug delivery molecule, comprising:
 (a) a polypeptide comprising a receptor binding domain of human heregulin-α, an adenovirus penton base protein, and a positively charged domain comprising a plurality of positively-charged amino acid residues that provide a net positive charge to the positively charged domain; and 
 (b) a corrole molecule bound to the polypeptide sequence: wherein the triple-negative breast cancer expresses HER3. 
   
     
     
         37 . The method of  claim 36 , wherein the corrole molecule includes Manganese (Mn), Iron (Fe), or Gallium (Ga). 
     
     
         38 . The method of  claim 36 , wherein the drug delivery molecule is HerMn, HerFe, or HerGa. 
     
     
         39 - 50 . (canceled) 
     
     
         51 . The method of  claim 36 , wherein the polypeptide molecule comprises a polylysine motif comprising a plurality of contiguous lysines. 
     
     
         52 . The method of  claim 51 , wherein the polylysine motif is a decalysine. 
     
     
         53 - 62 . (canceled) 
     
     
         63 . A method of inducing apoptosis in a triple-negative breast cancer cell, comprising:
 contacting the triple-negative breast cancer cell with a drug delivery molecule, comprising:
 (a) a polypeptide comprising a receptor binding domain of human heregulin-α, an adenovirus penton base protein, and a positively charged domain comprising a plurality of positively-charged amino acid residues that provide a net positive charge to the positively charged domain; and 
 (b) a corrole molecule bound to the polypeptide sequence wherein the triple-negative breast cancer expresses HER3. 
   
     
     
         64 . The method of  claim 63 , wherein the corrole molecule includes Manganese (Mn), Iron (Fe), Gallium (Ga). 
     
     
         65 . The method of  claim 63 , wherein the drug delivery molecule is HerMn, HerFe, or HerGa. 
     
     
         66 - 77 . (canceled) 
     
     
         78 . The method of  claim 63 , wherein the polypeptide molecule comprises a polylysine motif comprising a plurality of contiguous lysines. 
     
     
         79 . The method of  claim 78 , wherein the polylysine motif is a decalysine. 
     
     
         80 - 89 . (canceled) 
     
     
         90 . The method of  claim 63 , wherein the contacting is in vitro. 
     
     
         91 . The method of  claim 63 , wherein the contacting is in vivo. 
     
     
         92 - 93 . (canceled) 
     
     
         94 . The method of  claim 36 , wherein the corrole molecule is a sulfonated corrole molecule. 
     
     
         95 . The method of  claim 94 , wherein the sulfonated corrole molecule comprises manganese (Mn), iron (Fe), or gallium (Ga). 
     
     
         96 . The method of  claim 94 , wherein the sulfonated corrole molecule comprises Manganese (Mn). 
     
     
         97 . The method of  claim 96 , further comprising imaging the triple-negative breast cancer by magnetic resonance imaging (MRI). 
     
     
         98 . The method of  claim 63 , wherein the corrole molecule is a sulfonated corrole molecule. 
     
     
         99 . The method of  claim 98 , wherein the sulfonated corrole molecule comprises manganese (Mn), iron (Fe), or gallium (Ga). 
     
     
         100 . A method of killing a triple-negative breast cancer cell, comprising:
 contacting the triple-negative breast cancer cell with a drug delivery molecule, comprising:
 (a) a polypeptide comprising a receptor binding domain of human heregulin-α, an adenovirus penton base protein, and a positively charged domain comprising a plurality of positively-charged amino acid residues that provide a net positive charge to the positively charged domain; and 
 (b) a corrole molecule bound to the polypeptide sequence wherein the triple-negative breast cancer expresses HER3.