Acid-sensitive dextran prodrug: A higher molecular weight makes a better efficacy

The acid-sensitive polymer prodrugs have attracted increasing attention because of their selective intratumoral or intracellular drug release. Herein, two intracellular acid-sensitive dextran-doxorubicin (Dex-DOX) conjugates with similar drug binding rate were synthesized through the Schiff base reaction between the aldehyde group in the oxidized Dex with different lengths and the amino group of DOX. The amphiphilic Dex-DOX conjugates self-assembled into micellar nanoparticles in phosphate-buffered saline (PBS). The micelle of prodrug with longer Dex, that is, Dex_500k-DOX, exhibited smaller size, quicker drug release, higher cell internalization, and stronger tumor suppression with upregulated security in comparison with the one with shorter Dex, that is, Dex_40k-DOX. Therefore, the molecular weight of prodrug backbone could adjust the properties, and a higher molecular weight endowed the Dex-DOX conjugate with a better antitumor efficacy in a limited number of tested samples.