INCREASING THE THERAPEUTIC EFFICIENCY OF MACROPHAGE-TARGETED THERAPEUTIC AGENTS BY UP-REGULATING THE MANNOSE LECTIN ON MACROPHAGES

摘要

Compositions and methods for the enhancement of delivery in vivo and in vitro of therapeutic agents and other substances to cells, including macrophages, are provided. Pharmaceutical compositions comprise substances capable of increasing the amount of lectins on cell surfaces, and therapeutic agents such as enzymes, anti-viral compounds, biologic response modifiers, chemotherapeutic agents, vector molecules, and DNA fragments. Such agents and other substances can be targeted to cells for enhanced delivery by either conjugating them to saccharides specific for certain lectins, or by entrapping them in carriers such as liposomes, microparticles, microcapsules, or erythrocyte ghosts, which have lectin-specific saccharides on their surface. Such saccharides can either be conjugated directly, or can be present at the terminus of an oligosaccharide. Delivery can be further enhanced by administering to cells, either in vivo or in vitro, lectin-increasing effective amounts of substances capable of increasing the amount of lectins on cell surfaces. Also disclosed are methods for treating diseases, including metabolic storage disorders, viral diseases, and metastatic cancer, employing the up-regulation of lectins on cell surfaces in combination with the targeting of appropriate therapeutic agents, either by the use of lectin-specific saccharides conjugated thereto, or carriers which express such saccharides.