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Gdańsk University of Technology

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Synthetic strategies in construction of organic macromolecular carrier–drug conjugates

Many metabolic inhibitors, considered potential antimicrobial or anticancer drug candidates, exhibit verylimited ability to cross the biological membranes of target cells. The restricted cellular penetration ofthose molecules is often due to their highhydrophilicity. One of the possible solutions to this problem is aconjugation of an inhibitor with a molecular organic nanocarrier. The conjugate thus formed should beable to penetrate the membrane(s) by direct translocation, endocytosis or active transport mechanismsand once internalized, the active component could reach its intracellular target, either after release fromthe conjugate or in an intact form. Several such nanocarriers have been proposed so far, including macro-molecular systems, carbon nanotubes and dendrimers. Herein, we present a comprehensive review of thecurrent status of rational design and synthesis of macromolecular organic nanocarrier-drug conjugates,with special attention focused on the mode of coupling of a nanocarrier moiety with a“cargo”moleculethrough linking fragments of non-cleavable or cleavable type.

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