A Precise and Intelligent Nanomedicine for Salivary Adenoid Cystic Carcinoma Treatment by Combining Antivascular Photodynamic Therapy and Neuroinhibitory Chemotherapy
A Precise and Intelligent Nanomedicine for Salivary Adenoid Cystic Carcinoma Treatment by Combining Antivascular Photodynamic Therapy and Neuroinhibitory Chemotherapy
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DOI：
10.1002/adfm.202312732
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发表时间：
2023-12-15
影响因子：
19
通讯作者：
Wang，Yinsong
中科院分区：
文献类型：
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作者：
Chen，Qian;Han，Lu;Wang，Yinsong
涎腺腺样囊性癌(SACC)是最常见的涎腺恶性肿瘤之一。目前的临床治疗方法存在局限性，不能有效地预防SACC的发展和转移。血源性和神经播散性是SACC转移的两条主要途径。在这项研究中，一种精确而智能的纳米药物RCDT被设计出来，将抗血管光动力疗法和神经抑制化疗结合起来对抗SACC。通过聚乙二醇键和二硒化键之间的桥联将cRGD与氯化e6(Ce6)连接，合成了一种肿瘤血管靶向和活性氧物种(ROS)响应型光敏剂(RC)。将阿霉素(DOX)与神经靶向多肽Tet1通过可酸解的糖苷键偶联，合成了一种神经靶向pH响应型细胞毒前药(DT)。Rc和DT通过疏水相互作用组装成RCDT，从而屏蔽Tet1。在cRGD的引导和Ce6的光动力作用下，RCDT可以准确地破坏肿瘤的血管系统，同时通过断裂双硒键而解体暴露Tet1。在Tet1的引导下，解体的RCDT可以特异性地内化到神经元中，并释放DOX，通过裂解肼来发挥神经抑制作用。利用这些循序渐进的双靶向和双反应策略，RCDT可以有效地抑制SACC的生长和转移。
Salivary adenoid cystic carcinoma (SACC) is one of the most common salivary gland malignancies. Current clinical therapies have limitations and cannot efficiently prevent the SACC development and metastasis. Hematogenous and neural spread are the two major routes of SACC metastasis. In this study, a precise and intelligent nanomedicine, RCDT, is designed to combine antivascular photodynamic therapy and neuroinhibitory chemotherapy against SACC. A tumor vessel‐targeted and reactive oxygen species (ROS)‐responsive photosensitizer (RC) is synthesized by linking cRGD to chlorin e6 (Ce6) via a bridge between the poly(ethylene glycol) and diselenide bonds. A neural‐targeted and pH‐responsive cytotoxic prodrug (DT) is synthesized by conjugating doxorubicin (DOX) with Tet1, a neural‐targeting peptide, via an acidic‐cleavable hydrazone bond. RC and DT are assembled to form RCDT via hydrophobic interactions, thereby shielding Tet1. Under the guidance of cRGD and the photodynamic action of Ce6, RCDT can precisely disrupt the tumor vasculature and simultaneously disintegrate to expose Tet1 by rupturing the diselenide bond. Guided by Tet1, disintegrated RCDT can be specifically internalized into neurons and release DOX to exert neuroinhibitory effects by cleaving the hydrazone bond. Using these stepwise dual‐targeting and dual‐responsive strategies, RCDT can efficiently suppress the growth and metastasis of SACC.