Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN, USA.
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Nanomedicine. 2018 Jan;14(1):85-96. doi: 10.1016/j.nano.2017.08.020. Epub 2017 Sep 11.
In this work we hypothesized that the chemokine fractalkine can serve as a cancer molecular target. We engineered aptamer micelles functionalized with an outer poly(ethylene glycol) (PEG) corona, and investigated the extent and efficacy of using them as a targeting tool against fractalkine-expressing colon adenocarcinoma cells. In vitro cell binding results showed that aptamer micelles bound and internalized to fractalkine-expressing cancer cells with the majority of the micelles found free in the cytoplasm. Minimal surface binding was observed by healthy cells. Even though partial PEGylation did not prevent serum adsorption, micelles were highly resistant to endonuclease and exonuclease degradation. In vivo biodistribution studies and confocal studies demonstrated that even though both aptamer and control micelles showed tumor accumulation, only the aptamer micelles internalized into fractalkine-expressing cancer cells, thus demonstrating the potential of the approach and showing that fractalkine may serve as a specific target for nanoparticle delivery to cancer cells.
在这项工作中，我们假设趋化因子 fractalkine 可以作为癌症的分子靶点。我们设计了带有聚乙二醇（PEG）外壳的适体胶束，并研究了它们作为针对 fractalkine 表达的结肠腺癌细胞的靶向工具的程度和效果。体外细胞结合结果表明，适体胶束与 fractalkine 表达的癌细胞结合并内化，大多数胶束游离在细胞质中。健康细胞的表面结合很少。尽管部分 PEG 化不能阻止血清吸附，但胶束对核酸内切酶和核酸外切酶的降解具有很强的抵抗力。体内分布研究和共聚焦研究表明，尽管适体和对照胶束都显示出肿瘤聚集，但只有适体胶束内化到 fractalkine 表达的癌细胞中，从而证明了该方法的潜力，并表明 fractalkine 可能作为纳米颗粒递送到癌细胞的特定靶点。
