Novel amphiphilic linear polyglycidol derivative for targeted cell imaging and pH-responsive Oridonin delivery in cancer cells

Assessing drug effectiveness and safety relies on crucial in vivo monitoring of drug distribution. This process enhances treatment precision, minimizes adverse effects, and informs the development of innovative therapies. This study developed a novel tumor cell-sensitive polymeric amphiphile, Py-HLPG (Py-Hydrazone functionalized linear polyglycidol), through the conjugation of linear polyglycidol (LPG) with a hydrophobic pyrene-based luminescent moiety. The amphiphile was designed with acid-responsive properties for selective activation in acidic tumor microenvironments. In vitro release studies demonstrated a 5-fold increase in drug release under responsive conditions, significantly enhancing its tumor-targeting potential. Py-HLPG demonstrated excellent micellization capability with an ultralow CMC of 8.4 µM, indicating superior stability for drug delivery applications. The ORI@Py-HLPG micelles demonstrated dual functionality, enabling both precise cellular imaging and effective anticancer activity. At a concentration of 50 µg/mL, ORI@Py-HLPG treatment resulted in only 20% HepG2 cell (human hepatocellular carcinoma cell line) viability. These findings suggest promising potential for developing multifunctional theranostic probes combining detection, imaging, and therapeutic properties.