Targeting pulmonary epithelium using adrp

Abstract

This invention provides novel compositions and methods for the specific and/or preferential delivery of an effector (e.g. a drug or label) to an epithelial cell (e.g. a pulmonary epithelium). The compositions comprise an adipocyte differentiation-related protein (ADRP) attached to an effector thereby forming a chimeric moiety. The chimeric moiety is preferentially delivered to epithelial cells.

1 . A method of inhibiting the growth or proliferation of a tumor cell, said method comprising contacting said tumor cell with contacting said tumor cell with a composition comprising an adipocyte differentiation-related protein (ADRP) covalently coupled to, or complexed with, a lipid or liposome, wherein said lipid is complexed with, or said liposome contains, a cancer therapeutic. 
     
     
         2 . The method of  claim 1 , wherein said cancer therapeutic is selected from the group consisting of retinoic acid, a retinoic acid derivative, doxirubicin, vinblastine, vincristine, cyclophosphamide, ifosfamide, cisplatin, 5-fluorouracil, a camptothecin derivative, interferon, tamoxifen, and taxol. 
     
     
         3 . The method of  claim 1 , wherein said ADRP is a carboxyl terminal fragment of ADRP of sufficient length to induce transport of said lipid or liposome into an epithelial cell. 
     
     
         4 . The method of  claim 1 , wherein said ADRP is a full length ADRP. 
     
     
         5 . The method of  claim 1 , wherein said cancer comprises a small cell carcinoma. 
     
     
         6 . The method of  claim 1 , wherein said lipid or liposome is a neutral lipid or a liposome formed of neutral lipids. 
     
     
         7 . The method of  claim 1 , wherein said lipid or liposome is a neutral lipid or a liposome formed of neutral lipids comprising triacylglycerol. 
     
     
         8 . The method of  claim 1 , wherein said lipid or liposome is a multilamellar liposome. 
     
     
         9 . The method of  claim 1 , wherein said lipid or liposome is a unilamellar liposome. 
     
     
         10 . A method of preferentially delivering an effector to a tumor cell in a mammal, said method comprising:
 providing said effector in a liposome or complexed with a lipid, wherein said lipid or said liposome are complexed with or covalently attached to an adipocyte differentiation-related protein (ADRP);   administering said lipid or liposome to said mammal whereby said lipid or liposome is preferentially internalized by said tumor cell.   
     
     
         11 . The method of  claim 10 , wherein said ADRP is a full length ADRP. 
     
     
         12 . The method of  claim 10 , wherein said lipid or liposome is a neutral lipid or a liposome formed of neutral lipids. 
     
     
         13 . The method of  claim 10 , wherein said lipid or liposome is a neutral lipid or a liposome formed of neutral lipids comprising triacylglycerol. 
     
     
         14 . The method of  claim 10 , wherein said lipid or liposome comprises an agent selected from the group consisting of a retinoid, a prostanoids, an anti-inflammatories, a growth factor, a thiazolidinediones, a chemokine, and a chemotherapeutic. 
     
     
         15 . The method of  claim 10 , wherein said lipid or liposome is a multilamellar liposome. 
     
     
         16 . The method of  claim 10 , wherein said lipid or liposome is a unilamellar liposome. 
     
     
         17 . The method of  claim 10 , wherein said mammal is a human. 
     
     
         18 . The method of  claim 10 , wherein said tumor cell comprises a small cell carcinoma. 
     
     
         19 . The method of  claim 10 , wherein said effector is selected from the group consisting of a label, a cytotoxin, a drug, a prodrug, and a cytokine. 
     
     
         20 . The method of  claim 10 , wherein said effector is a cytotoxin selected from the group consisting of a  Diphtheria  toxin, a  Pseudomonas  exotoxin, a ricin, an abrin, and a thymidine kinase. 
     
     
         21 . The method of  claim 10 , wherein said effector is a detectable label selected from the group consisting of a radioactive label, a spin label, a colorimetric label, a fluorescent label, and a radio-opaque label. 
     
     
         22 . The method of  claim 10 , wherein said effector comprises an isotope selected from the group consisting of  99 Tc,  203 Pb,  67 Ga,  68 Ga,  72 As,  111 In,  113m In,  97 Ru,  62 Cu,  64 Cu,  52 Fe,  52 Mn,  51 Cr,  186 , Re,  188 Re,  77 As,  90 Y,  67 Cu,  169 Er,  121 Sn,  127 Te,  142 Pr,  143 Pr,  198 Au,  199 Au,  161 Tb,  109 Pd,  165 Dy,  151 Pm,  153 Sm,  157 Gd,  159 Gd,  166 Ho,  172 Tm,  169 Yb,  175 Yb,  177 Lu,  105 Rh, and  111 Ag. 
     
     
         23 . The method of  claim 10 , wherein said effector comprises an alpha emitter. 
     
     
         24 . The method of  claim 10 , wherein said effector is a drug selected from the group consisting of retinoic acid, a retinoic acid derivative, doxirubicin, vinblastine, vincristine, cyclophosphamide, ifosfamide, cisplatin, 5-fluorouracil, a camptothecin derivative, interferon, tamoxifen, and taxol.