Retinoblastoma (RB) is an aggressive tumor of the infant retina. However, the ineffective targeting of its theranostic agents results in poor imaging and therapeutic efficacy, which makes it difficult to identify and treat RB at an early stage. In order to improve the imaging and therapeutic efficacy, we constructed an RB-targeted artificial vesicle composite nanoparticle. In this study, the MnO₂ nanosponge (hMNs) was used as the core to absorb two fluorophore-modified DNAzymes to form the Dual/hMNs nanoparticle; after loaded with the artificial vesicle derived from human red blood cells, the RB-targeted DNA aptamers were modified on the surface, thus forming the Apt-EG@Dual/hMNs complex nanoparticle. The DNA aptamer endows this nanoparticle to target the nucleolin-overexpressed RB cell membrane specifically and enters cells via endocytosis. The nanoparticle could release fluorophore-modified DNAzymes and supplies Mn²⁺ as a DNAzyme cofactor and a magnetic resonance imaging (MRI) agent. Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.

中文翻译：

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功能性核酸基人工囊泡封装复合纳米粒子的构建及其在视网膜母细胞瘤靶向治疗中的应用

视网膜母细胞瘤（RB）是婴儿视网膜的一种侵袭性肿瘤。然而，其治疗诊断药物的靶向性不强，导致影像学和治疗效果不佳，导致RB的早期识别和治疗困难。为了提高成像和治疗效果，我们构建了RB靶向人工囊泡复合纳米粒子。本研究以MnO ₂纳米海绵(hMNs)为核心，吸附两种荧光团修饰的DNAzyme，形成Dual/hMNs纳米粒子。负载来自人红细胞的人工囊泡后，RB靶向DNA适体在表面进行修饰，从而形成Apt-EG@Dual/hMNs复合纳米颗粒。DNA适体赋予该纳米颗粒特异性靶向核仁素过度表达的RB细胞膜，并通过内吞作用进入细胞。该纳米颗粒可以释放荧光团修饰的 DNAzyme 并提供 Mn ²⁺作为 DNAzyme 辅因子和磁共振成像 (MRI) 试剂。随后，DNAzymes可以靶向两种不同的mRNA，从而实现荧光/MR双模成像和双基因治疗。该研究有望为眼肿瘤治疗学提供可靠且有价值的依据。