Method for enhancing transport of semiconductor nanocrystals across biological membranes

Abstract

Semiconductor nanoparticle complexes comprising semiconductor nanoparticles in association with cationic polymers are described. Also described are methods for enhancing the transport of semiconductor nanoparticles across biological membranes to provide encoded cells. The methods are particularly useful in multiplex settings where a plurality of encoded cells are to be assayed. Kits comprising reagents for performing such methods are also provided.

1 . A semiconductor nanoparticle complex comprising a semiconductor nanoparticle associated with a cationic polymer capable of enhancing the transport of the semiconductor nanoparticle across a biological membrane. 
     
     
         2 . The semiconductor nanoparticle complex of  claim 1 , wherein the semiconductor nanoparticle is a semiconductor nanocrystal. 
     
     
         3 . The semiconductor nanoparticle complex of  claim 2 , wherein the semiconductor nanocrystal comprises a core is selected from the group consisting of ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, AlAs, AlP, AlSb, AlS, Ge, Si, Pb, PbS, PbSe, an alloy thereof, and a mixture thereof. 
     
     
         4 . The semiconductor nanoparticle complex of  claim 4 , wherein the semiconductor nanocrystal core is CdSe. 
     
     
         5 . The semiconductor nanoparticle complex of  claim 3 , wherein the semiconductor nanocrystal core is surrounded by a semiconductor shell. 
     
     
         6 . The semiconductor nanoparticle complex of  claim 5 , wherein the semiconductor shell comprises a semiconductor material selected from the group consisting of ZnS, ZnSe, ZnTe, CdS, CdSe, CdTe, HgS, HgSe, HgTe, MgS, MgSe, MgTe, CaS, CaSe, CaTe, SrS, SrSe, SrTe, BaS, BaSe, BaTe, GaN, GaP, GaAs, GaSb, InN, InP, InAs, InSb, AlAs, AlP, AlSb, AlS, Ge, Si, Pb, PbS, PbSe, an alloy thereof, and a mixture thereof. 
     
     
         7 . The semiconductor nanoparticle complex of  claim 6 , wherein the semiconductor shell is ZnS. 
     
     
         8 . The semiconductor nanoparticle complex of  claim 1 , wherein the cationic polymer is tat peptide from the protein transduction domain of the HIV tat protein. 
     
     
         9 . The semiconductor nanoparticle complex of  claim 8 , wherein the tat peptide comprises the sequence RKKRRQRRR (SEQ ID NO: 1). 
     
     
         10 . The semiconductor nanoparticle complex of  claim 1 , wherein the cationic polymer has from 5 to 25 contiguous Lys and/or Arg residues. 
     
     
         11 . The semiconductor nanoparticle complex of  claim 1 , wherein the biological membrane is a cell membrane. 
     
     
         12 - 16 . (canceled) 
     
     
         17 . A method of enhancing the transport of a semiconductor nanoparticle across a biological membrane comprising contacting a cell with the semiconductor nanoparticle complex of  claim 1 , under conditions that provide for the transport of the semiconductor nanoparticle across the biological membrane. 
     
     
         18 - 23 . (canceled) 
     
     
         24 . A method of distinguishably identifying a cell, comprising:
 (a) providing a cell; and   (b) contacting the cell with a semiconductor nanoparticle complex according to  claim 1  under conditions in which the semiconductor nanoparticle is transported across the cell membrane to provide a labeled cell, thereby identifying the cell.   
     
     
         25 - 30 . (canceled) 
     
     
         31 . A method of identifying a cell in a mixed population of cells, comprising:
 (a) providing a first cell;   (b) contacting the cell with a semiconductor nanoparticle complex according to  claim 1  under conditions in which the semiconductor nanoparticle is transported across the cell membrane to provide an encoded first cell;   (c) mixing the encoded first cell with a second cell distinct therefrom to form a mixed population of cells;   (d) culturing the mixed population of cells;   (e) exposing the cultured mixed population of cells to an excitation energy source; and   (f) detecting a semiconductor nanoparticle code to identify the encoded cell.   
     
     
         32 - 37 . (canceled) 
     
     
         38 . A kit comprising a semiconductor nanoparticle complex according to  claim 1  and instructions for preparing encoded cells using the semiconductor nanoparticle complex. 
     
     
         40 - 41 . (canceled)