胶质母细胞瘤是最常见的原发性颅内肿瘤之一，其特点是死亡率高、预后差。尽管目前大多数药物疗效有限且毒性显着，但化疗仍然是神经胶质瘤的关键治疗策略。本研究重点关注前一阶段合成的 cRGD-siEGFR 偶联化合物。前期研究表明cRGD-siEGFR分子具有一定的靶向性和抗肿瘤特性，但存在靶向性不足、疗效低、肾毒性高等问题。为了增强抗肿瘤功效并减轻副作用，开发了一种 pH 响应性、长循环和高度靶向的 siRNA 递送系统，即 cRGD-PEG-siEGFR 缀合物。检查了 cRGD-PEG-siEGFR 的靶向、抗肿瘤作用和生物分布。结果表明，cRGD-PEG-siEGFR被αvβ3阳性U87MG细胞有效摄取，特异性沉默EGFR基因表达，并表现出抗肿瘤作用。在正常生理条件下，它避免被正常细胞摄取，从而减少副作用。此外，体内生物分布实验表明，与cRGD-siEGFR相比，cRGD-PEG-siEGFR显着减少肾脏蓄积并表现出延长的循环。因此，cRGD-PEG-siRNA 成为一种有前途的候选药物，具有长循环、高靶向性、pH 响应性和显着的抗肿瘤功效。

Glioblastoma ranks among the most prevalent primary intracranial tumors, characterized by high mortality and poor prognosis. Chemotherapy remains a key treatment strategy for gliomas, though most current drugs suffer from limited efficacy and significant toxicity. This study focuses on a cRGD-siEGFR coupling compound synthesized in a previous stage. Prior research indicated that cRGD-siEGFR molecules exhibited certain targeting and antitumor properties but faced issues of inadequate targeting, low efficacy, and high renal toxicity. To enhance antitumor efficacy and mitigate side effects, a pH-responsive, long-circulating, and highly targeted siRNA delivery system, the cRGD-PEG-siEGFR conjugate, was developed. The targeting, antitumor effects, and biological distribution of cRGD-PEG-siEGFR were examined. The results demonstrated that cRGD-PEG-siEGFR was effectively taken up by αvβ3-positive U87MG cells, specifically silenced EGFR gene expression, and exhibited antitumor effects. In normal physiological conditions, it avoided uptake by normal cells, thereby reducing side effects. Furthermore, in vivo biodistribution experiments revealed that cRGD-PEG-siEGFR, compared to cRGD-siEGFR, significantly decreased renal accumulation and exhibited prolonged circulation. Consequently, cRGD-PEG-siRNA emerges as a promising drug candidate with attributes of long circulation, high targeting, pH responsiveness, and substantial antitumor efficacy.