Andreozzi Elisa, Antonelli Antonella, Cangiotti Michela, Canonico Barbara, Sfara Carla, Pianetti Anna, Bruscolini Francesca, Sahre Karin, Appelhans Dietmar, Papa Stefano, Ottaviani Maria Francesca
Department of Biomolecular Sciences, University of Urbino Carlo Bo , Via Saffi 2, 61029 Urbino, Italy.
Department of Pure and Applied Sciences, University of Urbino Carlo Bo , Via Ca' Le Suore 2/4, 61029 Urbino, Italy.
Bioconjug Chem. 2017 Feb 15;28(2):524-538. doi: 10.1021/acs.bioconjchem.6b00635. Epub 2017 Jan 26.
Poly(propyleneimine) glycodendrimers fully modified with maltose units were administered to different cancer cell lines and their effect on cell viability was evaluated by using MTS assay and flow cytometry. The mechanism of dendrimer-cell interactions was investigated by the electron paramagnetic resonance (EPR) technique by using a new nitroxide-conjugated glycodendrimer. The nitroxide groups did not modify both the biological properties (cell viability and apoptosis degree) of the dendrimers in the presence of the cells and the dendrimer-cell interactions. Since this class of dendrimers is already known to be biocompatible for human healthy cells, noncancer cells such as human peripheral blood mononuclear cells (PBMCs) and macrophages were also treated with the glycodendrimer, and EPR spectra of the nitroxide-conjugated glycodendrimer were compared for cancer and noncancer cells. It was found that this dendrimer selectively affects the cell viability of tumor cells, while, surprisingly, PBMC proliferation is induced. Moreover, H-bond-active glycodendrimer-cell interactions were different for the different cancer cell lines and noncancer cells. The nitroxide-conjugated glycodendrimer was able to interact with the cell membrane and eventually cross it, getting in contact with cytosol antioxidants. This study helps to clarify the potential anticancer effect of this class of dendrimers opening to future applications of these macromolecules as new antitumor agents.
将用麦芽糖单元完全修饰的聚（丙烯亚胺）糖树枝状大分子给予不同的癌细胞系，并通过MTS测定法和流式细胞术评估其对细胞活力的影响。通过使用一种新的氮氧化物共轭糖树枝状大分子，利用电子顺磁共振（EPR）技术研究了树枝状大分子与细胞相互作用的机制。在细胞存在的情况下，氮氧化物基团既不改变树枝状大分子的生物学特性（细胞活力和凋亡程度），也不改变树枝状大分子与细胞的相互作用。由于已知这类树枝状大分子对人类健康细胞具有生物相容性，因此也用糖树枝状大分子处理了非癌细胞，如人类外周血单核细胞（PBMC）和巨噬细胞，并比较了癌症细胞和非癌细胞的氮氧化物共轭糖树枝状大分子的EPR光谱。结果发现，这种树枝状大分子选择性地影响肿瘤细胞的细胞活力，而令人惊讶的是，它能诱导PBMC增殖。此外，不同癌细胞系和非癌细胞的氢键活性糖树枝状大分子与细胞的相互作用也不同。氮氧化物共轭糖树枝状大分子能够与细胞膜相互作用并最终穿过细胞膜，与胞质溶胶抗氧化剂接触。这项研究有助于阐明这类树枝状大分子的潜在抗癌作用，为这些大分子作为新型抗肿瘤药物的未来应用开辟了道路。
