Functionalizing Sgc8‐Paclitaxel Conjugates with F‐Base Modifications: Targeted Drug Delivery with Optimized Cardiac Safety

Abstract

AbstractRecent advancements in cancer treatment have improved patient prognoses, but chemotherapy induced cardiotoxicity remains a prevalent concern. This study explores the potential of F‐base‐modified aptamers for targeted drug delivery, focusing on their impact on cardiotoxicity. From the phosphoramidite, F‐base‐functionalized Sgc8‐F23 was prepared in an automated and programmable way, which was further reacted with paclitaxel (PTX) to give the F‐base‐ modified aptamer Sgc8‐paclitaxel conjugates (Sgc8‐F23‐PTX) efficiently. The conjugate exhibited prolonged circulation time and enhanced efficacy as a precision anticancer drug delivery system. Echocardiographic assessments revealed no exacerbation of cardiac dysfunction after myocardial infarction (MI) and no pathological changes or increased apoptosis in non‐infarcted cardiac regions. Autophagy pathway analysis showed no discernible differences in Sgc8‐F23‐PTX‐treated cardiomyocytes compared with controls, in contrast to the increased autophagy with nanoparticle albumin‐bound‐paclitaxel (Nab‐PTX). Similarly, apoptosis analysis showed no significant differences. Moreover, Sgc8‐F23‐PTX exhibited no inhibitory effect on hERG, hNav1.5, or hCav1.2 channels. These findings suggest the safety and efficacy of F‐base‐modified Sgc8 aptamers for targeted drug delivery with potential clinical applications. Further research is warranted for clinical translation and exploration of other drug carriers.