Electrochemical monitoring of TMZ derivative release from a novel chitosan-modified polymeric carrier for targeted glioma therapy

As the most frequent malignant tumors of the central nervous system, gliomas exhibit poor prognosis due to aggressive progression and treatment resistance, highlighting the urgent need for new therapeutic strategies targeting molecules such as LRP1B and ERBB4, whose dysregulation is closely associated with glioma progression and poor clinical outcomes. In this study, carboxymethyl chitosan (Fru) was functionally modified with 3-aminopropyltrimethoxysilane (APTMS) to establish a vector for the Fru-APTMS coordination polymer (CP1). A Temozolomide (TMZ) analog, compound
1
, was subsequently loaded to form a multifunctional nanodrug delivery system, denoted as Fru-APTMS@CP1@1. Raman and Fourier transform infrared (FT-IR) spectroscopy verified the structural characterization of the composites. Cyclic voltammetry (CV) in a [Fe(CN)
6
]
3−/4−
electrolyte revealed a significantly enhanced peak current of 133 mA, corresponding to a large electrochemically active surface area (EASA) (0.1866 cm
2
) and excellent electron transfer capability. Furthermore, differential pulse voltammetry (DPV) demonstrated a favorable linear response (R
2
= 0.9894) and a low detection limit (0.02229 μM), indicating high electrochemical sensitivity. In biological evaluation, FRU-APTMS@CP1@1 significantly inhibited glioma cell proliferation by synergistically regulating the expression of LRP1B and ERBB4, suggesting a multitargeted anti-tumor mechanism.