Aix-Marseille University, INSERM, INRA, Center de Recherche en Cardiovasculaire et Nutrition (C2VN), 13385 Marseille, France.
Aix-Marseille University, Centre Européen de Recherche en Imagerie Médicale (CERIMED), 13005 Marseille, France.
Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11454-11459. doi: 10.1073/pnas.1812938115. Epub 2018 Oct 22.
Bioimaging plays an important role in cancer diagnosis and treatment. However, imaging sensitivity and specificity still constitute key challenges. Nanotechnology-based imaging is particularly promising for overcoming these limitations because nanosized imaging agents can specifically home in on tumors via the "enhanced permeation and retention" (EPR) effect, thus resulting in enhanced imaging sensitivity and specificity. Here, we report an original nanosystem for positron emission tomography (PET) imaging based on an amphiphilic dendrimer, which bears multiple PET reporting units at the terminals. This dendrimer is able to self-assemble into small and uniform nanomicelles, which accumulate in tumors for effective PET imaging. Benefiting from the combined dendrimeric multivalence and EPR-mediated passive tumor targeting, this nanosystem demonstrates superior imaging sensitivity and specificity, with up to 14-fold increased PET signal ratios compared with the clinical gold reference 2-fluorodeoxyglucose ([F]FDG). Most importantly, this dendrimer system can detect imaging-refractory low-glucose-uptake tumors that are otherwise undetectable using [F]FDG. In addition, it is endowed with an excellent safety profile and favorable pharmacokinetics for PET imaging. Consequently, this dendrimer nanosystem constitutes an effective and promising approach for cancer imaging. Our study also demonstrates that nanotechnology based on self-assembling dendrimers provides a fresh perspective for biomedical imaging and cancer diagnosis.
生物成像在癌症的诊断和治疗中起着重要作用。然而，成像的灵敏度和特异性仍然是关键的挑战。基于纳米技术的成像是克服这些限制的一个很有前途的方法，因为纳米级的成像剂可以通过“增强渗透和保留”（EPR）效应特异性地靶向肿瘤，从而提高成像的灵敏度和特异性。在这里，我们报告了一种基于两亲性树枝状大分子的新型正电子发射断层扫描（PET）成像纳米系统，该大分子在末端带有多个 PET 报告单元。这种树枝状大分子能够自组装成小而均匀的纳米胶束，在肿瘤中积累，从而实现有效的 PET 成像。受益于树枝状大分子的多价结合和 EPR 介导的被动肿瘤靶向，该纳米系统表现出优异的成像灵敏度和特异性，与临床金标准 2-氟脱氧葡萄糖（[F]FDG）相比，PET 信号比增加了 14 倍。最重要的是，该树枝状大分子系统能够检测到成像耐药的低葡萄糖摄取肿瘤，而使用[F]FDG 则无法检测到这些肿瘤。此外，它还具有良好的安全性和用于 PET 成像的药代动力学特性。因此，这种树枝状大分子纳米系统为癌症成像提供了一种有效且有前途的方法。我们的研究还表明，基于自组装树枝状大分子的纳米技术为生物医学成像和癌症诊断提供了新的视角。
