CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences , Suzhou 215163, China.
University of Chinese Academy of Sciences , Beijing 100049, China.
ACS Nano. 2017 Dec 26;11(12):12732-12741. doi: 10.1021/acsnano.7b07486. Epub 2017 Nov 17.
There is a pressing need to develop nanoplatforms that integrate multimodal therapeutics to improve treatment responses and prolong the survival of patients with unresectable hepatocellular carcinoma (HCC). Mesoporous silica-coated gold nanomaterials have emerged as a novel multifunctional platform combining tunable surface plasmon resonance and mesoporous properties that exhibit multimodality properties in cancer theranostics. However, their reduced radiation-absorption efficiency and limited surface area hinder their further radiochemotherapeutic applications. To address these issues, we designed Janus-structured gold-mesoporous silica nanoparticles using a modified sol-gel method. This multifunctional theranostic nanoplatform was subsequently modified via the conjugation of folic acid for enhanced HCC targeting and internalization. The loaded anticancer agent doxorubicin can be released from the mesopores in a pH-responsive manner, facilitating selective and safe chemotherapy. Additionally, the combination of chemotherapy and radiotherapy induced synergistic anticancer effects in vitro and exhibited remarkable inhibition of tumor growth in vivo along with significantly reduced systematic toxicity. Additionally, the Janus NPs acted as targeted computed tomography (CT)-imaging agents for HCC diagnosis. Given their better performance in chemoradiotherapy and CT imaging as compared with that of their core-shell counterparts, this new nanoplatform designed with dual functionalities provides a promising strategy for unresectable HCC theranostics.
目前迫切需要开发能够整合多种治疗方法的纳米平台,以提高无法切除的肝细胞癌(HCC)患者的治疗反应并延长其生存期。介孔硅包覆的金纳米材料作为一种新型多功能平台,结合了可调谐的表面等离子体共振和介孔性能,在癌症治疗学中表现出多种模式的特性。然而,其辐射吸收效率降低和有限的表面积限制了它们在放化疗中的进一步应用。为了解决这些问题,我们使用改进的溶胶-凝胶法设计了具有 Janus 结构的金介孔硅纳米粒子。随后,通过连接叶酸对这种多功能治疗性纳米平台进行修饰,以增强对 HCC 的靶向性和内化作用。载药的阿霉素可以通过介孔的 pH 响应方式释放,从而促进选择性和安全性化疗。此外,体外化疗和放疗的联合作用诱导了协同的抗癌作用,并在体内显著抑制了肿瘤生长,同时系统毒性明显降低。此外,Janus NPs 还可以作为 HCC 诊断的靶向计算机断层扫描(CT)成像剂。与核壳结构的纳米粒子相比,这种具有双重功能的新型纳米平台在化学放疗和 CT 成像方面表现出更好的性能,为不可切除的 HCC 治疗学提供了一种很有前途的策略。