Treatment of artificially induced storage disease with lysosomotropic microparticles

An artificial storage disease has been induced in mice by intravenously injecting 14C-labelled crosslinked dextran. The dextran was essentially taken up in the spleen and liver by cells belonging to the reticuloendothelial system and stored there in the lysosomes. Soluble dextranase, when given intravenously, had no effect on the stored dextran as judged by the radioactivity content of the tissues. However, when the dextranase was immobilized in microparticles of polyacryldextran and injected intravenously, the clearance of the radiolabelled dextran was significantly catalyzed. The lysosomotropic microparticles carried the enzyme to the lysosomes, where the microparticles were destroyed by the dextranase, which thereafter digested the stored 14C-dextran. The results illustrate the use of "self-destroying" microparticles as a lysosome-directed carrier of enzymes.