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新型载 Bcl2siRNA 和量子点的脂质纳米复合物用于表皮生长因子受体靶向的抗癌联合治疗。

Novel Lipid Nanocomplex Co-Carrying Bcl2 siRNA and Quantum Dots for EGF Receptor-Targeted Anti-Cancer Theranosis.

机构信息

Department of Medicine, Brown University, Providence, RI 02903, USA.

Department of Biomedical Laboratory Science, Yonsei University, Wonju 26496, Republic of Korea.

出版信息

Int J Mol Sci. 2024 Jun 6;25(11):6246. doi: 10.3390/ijms25116246.

Abstract

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.

摘要

许多不同类型的纳米颗粒已被提议用于肿瘤靶向治疗。然而,大多数系统都是通过一系列复杂的过程制备的,甚至无法克服血免疫屏障。为了对癌症进行准确的诊断和有效的治疗,我们在此提出了脂质胶束结构捕获量子点(QD)用于癌症治疗。QD/脂质胶束(QDM)是通过简单的自组装程序制备的,然后与抗表皮生长因子受体(EGFR)抗体偶联以进行肿瘤靶向。作为治疗剂,Bcl2 siRNA-胆固醇缀合物被装载在 QDM 的表面上。含有 Bcl2 siRNA 的 EGFR 定向 QDM,即免疫 QDM/siBcl2(iQDM/siBcl2),在培养物以及在小鼠异种移植中显示出更有效地向靶人类结肠癌细胞递送 QD 和 siBcl2。iQDM/siBcl2 的有效体内靶向导致 siBcl2 对小鼠靶癌症的治疗效果得到更大增强。基于这些结果,抗 EGFR QDM 捕获治疗性 siRNA 可被提议作为肿瘤靶向治疗的替代方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e838/11172456/bb8b27875a83/ijms-25-06246-g001.jpg

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