Differential tumor cell cytotoxicity via contact with coated cerium oxide nanoparticles

Abstract

Differential surface-charge-dependent localization of nanoceria in normal cells and cancer cells plays a critical role in the toxicity profile of a nanoceria particle. Engineered surface-coated cerium oxide nanoparticles with different surface charges that are positive, negative and neutral provide therapeutic results for normal and cancer cell lines. Results show that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g. cytoplasm and lysosomes) depending on the nanoparticle surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticle cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cell lines. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells.

We claim: 
     
         1 . A method for non-cytotoxic delivery of particles to cells, comprising:
 providing at least one cerium oxide nanoparticle, wherein at least one polymer coating is bound to said cerium oxide nanoparticle, wherein said polymer coating provides a surface charge that is at least one of a positive charge and a neutral charge; and   exposing said cerium oxide nanoparticle, to at least one cell.   
     
     
         2 . The method of  claim 1 , wherein said polymer coating comprises dextran that provides the neutral charge. 
     
     
         3 . The method of  claim 1 , wherein said polymer coating comprises aminated polyacrylic acid that provides the positive charge. 
     
     
         4 . The method of  claim 1 , wherein said polymer coating further comprises a fluorescent dye. 
     
     
         5 . The method of  claim 4 , wherein the dye is 1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate (DiI). 
     
     
         6 . The method of  claim 1 , wherein the at least one cell is a normal, non-transformed cell or malignant, transformed cell. 
     
     
         7 . The method of  claim 6 , wherein the at least one cell is a malignant breast carcinoma cell.