Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Sydney, Australia; Australian Centre for NanoMedicine, ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of New South Wales, NSW, Sydney, Australia.
College of Pharmacy and Medical Sciences, Hebron University, Hebron, Palestine.
Eur J Pharm Biopharm. 2018 Jan;122:176-185. doi: 10.1016/j.ejpb.2017.11.005. Epub 2017 Nov 10.
Hybrid nanocarrier consisting in nanographene oxide coated by a dextran-catechin conjugate was proposed in the efforts to find more efficient Neuroblastoma treatment with Doxorubicin chemotherapy. The dextran-catechin conjugate was prepared by immobilized laccase catalysis and its peculiar reducing ability exploited for the synthesis of the hybrid carrier. Raman spectra and DSC thermograms were recorded to check the physicochemical properties of the nanohybrid, while DLS measurements, SEM, TEM, and AFM microscopy allowed the determination of its morphological and dimensional features. A pH dependent Doxorubicin release was observed, with 30 and 75% doxorubicin released at pH 7.4 and 5.0, respectively. Viability assays on parental BE(2)C and resistant BE(2)C/ADR cell lines proved that the high anticancer activity of dextran-catechin conjugate (IC 19.9 ± 0.6 and 18.4 ± 0.7 µg mL) was retained upon formation of the nanohybrids (IC 24.8 ± 0.7 and 22.9 ± 1 µg mL). Combination therapy showed a synergistic activity between doxorubicin and either bioconjugate or nanocarrier on BE(2)C. More interestingly, on BE(2)C/ADR we recorded both the reversion of doxorubicin resistance mechanism as a consequence of decreased P-gp expression (Western Blot analysis) and a synergistic effect on cell viability, confirming the proposed nanohybrid as a very promising starting point for further research in neuroblastoma treatment.
一种由纳米氧化石墨烯包裹葡聚糖-儿茶素缀合物组成的杂化纳米载体被提出，旨在寻找更有效的神经母细胞瘤治疗方法，并用多柔比星化疗。葡聚糖-儿茶素缀合物通过固定化漆酶催化制备，并利用其特殊的还原能力合成杂化载体。记录拉曼光谱和差示扫描量热法（DSC）热谱图以检查纳米杂化物的物理化学性质，而动态光散射（DLS）测量、扫描电子显微镜（SEM）、透射电子显微镜（TEM）和原子力显微镜（AFM）显微镜则允许确定其形态和尺寸特征。观察到 pH 依赖性多柔比星释放，分别在 pH 7.4 和 5.0 时释放 30%和 75%的多柔比星。对亲本 BE(2)C 和耐药 BE(2)C/ADR 细胞系进行的活力测定证明，葡聚糖-儿茶素缀合物（IC 19.9±0.6 和 18.4±0.7 µg mL）的高抗癌活性在形成纳米杂化物后得以保留（IC 24.8±0.7 和 22.9±1 µg mL）。联合治疗显示多柔比星与生物缀合物或纳米载体在 BE(2)C 上具有协同活性。更有趣的是，在 BE(2)C/ADR 上，我们记录了多柔比星耐药机制的逆转，这是由于 P-糖蛋白表达降低（Western Blot 分析），以及对细胞活力的协同作用，证实了所提出的纳米杂化物作为神经母细胞瘤治疗进一步研究的非常有前途的起点。
