Light responsive quantum dot drug delivery system

Abstract

Compositions and methods are described for delivery of drugs to desired tissues via soluble quantum dots.

1 - 20 . (canceled) 
     
     
         21 . A quantum dot (QD) drug delivery system (QD-DDS) comprising:
 (i) a water soluble QD nanoparticle comprising a core semiconductor material or a core/shell semiconductor material and an outer layer, the outer layer comprising:
 an inner hydrophobic domain, 
 a middle amphiphilic domain, and 
 an outer hydrophilic domain; and 
   ii) a drug molecule located at the inner hydrophobic domain, the middle amphiphilic domain or the outer hydrophilic domain of the outer layer,   
       wherein the drug molecule is releasable from the outer layer upon excitation of the QD nanoparticle. 
     
     
         22 . The QD-DDS of  claim 21 , wherein the water soluble QD nanoparticle comprises a core formed of a cadmium free semiconductor material. 
     
     
         23 . The QD-DDS of  claim 21 , wherein the water soluble QD nanoparticle comprises an alloyed semiconductor material having a bandgap value that increases outwardly by graded alloying. 
     
     
         24 . The QD-DDS of  claim 21 , wherein the outer layer comprises a ligand interactive agent and a surface modifying ligand. 
     
     
         25 . The QD-DDS of  claim 23 , wherein the ligand interactive agent and the surface modifying ligand are crosslinked. 
     
     
         26 . The QD-DDS of  claim 24 , wherein the ligand interactive agent is selected from C 8-20  fatty acids, C 8-20  fatty acid esters, cholesterol, and any combination thereof. 
     
     
         27 . The QD-DDS of  claim 26 , wherein the C 8-20  fatty acid ester ligand interactive agent is isopropyl myristate. 
     
     
         28 . The QD-DDS of  claim 26 , wherein the surface modifying ligand is a monomethoxy polyethylene oxide. 
     
     
         29 . The QD-DDS of  claim 21 , wherein the nanoparticle further comprises capping ligands and wherein the drug molecules are physically entrapped in the capping ligands of the nanoparticle. 
     
     
         30 . The QD-DDS of  claim 29 , wherein the capping ligands are selected from the group consisting of thiol, carboxyl, amine, phosphine, phosphine oxide, phosphonic acid, phosphinic acid, imidazole, hydroxy, thio ether, and calixarene groups. 
     
     
         31 . The QD-DDS of  claim 21 , wherein the drug molecule is hydrophobic with an octanol-water partition coefficient (log P) of greater than 0. 
     
     
         32 . The QD-DDS of  claim 21 , wherein the drug molecule is hydrophobic with an octanol-water partition coefficient (log P) of greater than 1. 
     
     
         33 . The QD-DDS of  claim 21 , wherein the drug molecule is released upon excitation of the water soluble QD with an excitation source selected from a normal blue light, UV light, laser light, LED light, multiphoton excitation, and an electrical current. 
     
     
         34 . The QD-DDS of  claim 21 , wherein the QD is derivatized with a targeting ligand prior to loading with the drug molecule. 
     
     
         35 . The QD-DDS of  claim 34 , wherein the targeting ligand is a monoclonal antibody directed to a target selected from the group consisting of carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR; also known as ERBB1), ERBB2 (also known as HER2), ERBB3, MET (also known as HGFR), insulin-like growth factor 1 receptor (IGF1R), ephrin receptor A3 (EPHA3), tumour necrosis factor (TNF)-related apoptosis-inducing ligand receptor 1 (TRAILR1; also known as TNFRSF10A), TRAILR2 (also known as TNFRSF10B), receptor activator of nuclear factor-κB ligand (RANKL; also known as TNFSF11), VEGF receptor (VEGFR), integrin αVβ3, integrin α5β1, fibroblast activation protein (FAP), tenascin, CD20, CD30, CD33, CD52, EpCAM, gpA33, Mucins, TAG-72, carbonic anhydrase IX (CAIX), PSMA, folate-binding protein, gangliosides GD2, GD3 and GM2, PD-L2, and telomerase subunits. 
     
     
         36 . The QD-DDS of  claim 21 , wherein water soluble QD nanoparticle comprises a semiconductor material selected from the group of materials consisting of ZnS, ZnSe, ZnTe, InP, InSb, AlP, AlS, AlSb, GaN, GaP, GaSb, PbS, PbSe, AgInS 2 , AgS, CuInS 2 , Si, Ge, alloys and doped derivatives thereof, and any combination thereof. 
     
     
         37 . The QD-DDS of  claim 21 , wherein the water soluble QD comprises a semiconductor material comprising a heavy metal, wherein the heavy metal is selected from the group consisting of cadmium (Cd), lead (Pb), mercury (Hg), vanadium (V) and arsenic (As), alloys and doped derivatives thereof, and any combination thereof. 
     
     
         38 . A method of treating a target tissue comprising administering a drug loaded QD-DDS of  claim 21  and administering light to the target tissue sufficient to excite the QD and induce release of the drug from QD-DDS. 
     
     
         39 . The method of  claim 38 , wherein the drug delivery system is used to diagnose, treat, cure, mitigate, or prevent disease states of humans, animals, plants, and other organisms. 
     
     
         40 . The method of  claim 38 , wherein the drug delivery system is administered:
 (i) systemically by a route selected from intraarterial, intravenous, intraperitoneal, intrathecal, subcutaneous, intramuscular, intratumoral, oral, sublingual, nasal, rectal, epidural and pulmonary routes; or   (ii) during a surgical operation by direct instillation or by spraying a target tissue.