The anti-tumor effect of chinese medicine extracts camptothecin -AS1411 system

The AS1411 aptamer has shown great potential in the development of targeted anti-tumor drug delivery systems. Camptothecin (CPT, Xǐshù Jiǎn) , a cytotoxic quinoline alkaloid first isolated from the traditional Chinese medicine Camptotheca acuminata (Xǐshù), has been extensively used in various Chinese medicinal preparations including Xi Shu Injection and compound formulations combined with other herbs for cancer treatment. Despite its potent antitumor activity demonstrated in both traditional applications and modern clinical studies, the clinical application of CPT is limited by poor water solubility, low stability, and lack of tumor selectivity. Although some studies have combined AS1411 with chemotherapeutic drugs, the precise binding mechanism between the AS1411 G-quadruplex and small molecule drugs like CPT remains unclear. A systematic investigation into their interaction is crucial for the rational design of efficient and targeted drug delivery systems that can enhance the therapeutic potential of this important TCM-derived compound. In this work, we first synthesized a CPT-AS1411 complex and confirmed its formation. Subsequently, we employed a suite of biophysical techniques to decipher the binding mechanism between CPT and the AS1411 G-quadruplex. UV–Vis absorption and steady-state fluorescence spectroscopy were used to verify complex formation and determine the quenching constant. Ethidium bromide (EtBr) displacement assays were conducted to probe the binding mode (e.g., intercalation or groove binding). Circular dichroism (CD) spectroscopy was utilized to monitor conformational changes in the AS1411 structure upon CPT binding. Furthermore, the effects of ionic strength and the stability of the complex under different storage conditions were evaluated. UV–Vis and fluorescence spectroscopy confirmed the formation of the CPT-AS1411 complex. The calculated quenching constant (K∼SV∼ = 0.5135 M⁻¹, K∼q∼ = 5.135 × 10⁷ M⁻¹·S⁻¹) indicated a static quenching process, suggesting the formation of a ground-state complex. EtBr displacement studies and CD spectral analysis collectively demonstrated a non-intercalative binding mode between CPT and AS1411. Investigations into ionic strength revealed that electrostatic interactions played a minor role in complex formation. Stability studies indicated that the CPT-AS1411 complex was more stable when stored at -4 °C compared to room temperature. This study comprehensively elucidates the non-intercalative binding mechanism between CPT and the AS1411 G-quadruplex through multi-spectroscopic methods. Our findings provide crucial molecular-level insights and a solid experimental foundation for the future development of AS1411-based targeted delivery systems for camptothecin and its derivatives, potentially enhancing their therapeutic efficacy and reducing systemic toxicity.