Inorganic nanoparticle monoclonal antibody conjugates

Objectives We used a model system of radiolabeled quantum dots to document the competition between efficient vascular targeting and interaction of NP with the reticulo-endothelial (RE) system. Such a nanoparticle system may be useful for delivery of ²²⁵Ac.

Methods CdTe(^125mTe)-NP capped with ZnS were derivitized with mercaptoacetic acid and conjugated to MAb201B that binds to murine thrombomodulin expressed in the lumen of lung blood vessels. The MAb targeted NP were tested in vivo by SPECT/CT imaging, autoradiography and std organ biodistribution. Biodistribution was also determined in mice depleted of phagocytic cells by clodronate-loaded liposomes.

Results NPs-MAb 201B retained ^125mTe and antibody activity and accumulated in lung (>400 %ID/g) within 1 h of iv injection, where control antibody-NPs did not. In a few hours, a large fraction of lung-targeted NPs redistributed to spleen and liver or excreted. Removal of NPs from circulation by phagocytic cells was confirmed by comparing biodistribution of targeted NPs in normal mice vs those depleted of phagocytic cells. In clodronate liposomes-treated mice, loss of the targeted NP from lung was inhibited by several fold at 24 h, while accumulation in liver and spleen remained constant.

Conclusions Result indicates that targeting of NPs preparations is a competition between the effectiveness of the targeting agent and the natural tendency for RE uptake of the particles.