School of Pharmacy, Fudan University , Shanghai , China.
J Drug Target. 2014 Jan;22(1):76-85. doi: 10.3109/1061186X.2013.839687. Epub 2013 Oct 4.
Cancer nanotherapeutics are changing the landscape of tumor treatment and used to circumvent limitations of conventional chemotherapy, such as non-specificity and low bioavailability. Reconstituted high density lipoproteins (rHDL) system is one of the most promising targeting delivery systems of chemotherapeutic drugs toward tumors. Here, we developed recombined high-density lipoprotein which can be functionalized to deliver doxorubicin intracellular with a higher efficiency. The cellular viability assay showed that the rHDL/Dox nanovectors had an enhanced efficiency in inhibiting the cell viability of hepatocellular carcinoma cell lines HepG2 and SMMC-7721. FACS and confocal microscopy was used to observe the doxorubicin delivery into cancer cells. Intracellular drug accumulation analysis confirmed that treatment of rHDL/Dox nanovectors resulted in higher intracellular doxorubicin concentration to the levels exceeding that of free drug. On the premise of efficient drug delivery, rHDL/Dox nanovectors have been preliminarily demonstrated effective inducing of cytotoxic effect and cell apoptosis to both of the cell lines in vitro. Tissue distribution experiment showed that rHDL/Dox nanovectors could also deliver doxorubicin to liver effectively. So, we proposed that this lipoprotein-based strategy holds promise for a safer and more efficient delivery of chemotherapeutic agents in the treatment of hepatocellular carcinoma.
癌症纳米治疗正在改变肿瘤治疗的格局，用于克服传统化疗的局限性，如非特异性和低生物利用度。再构成的高密度脂蛋白（rHDL）系统是最有前途的化疗药物靶向递药系统之一。在这里，我们开发了可以被功能化以更高效地将阿霉素递送至细胞内的重组高密度脂蛋白。细胞活力测定表明，rHDL/阿霉素纳米载体在抑制肝癌细胞系 HepG2 和 SMMC-7721 的细胞活力方面具有更高的效率。FACS 和共聚焦显微镜用于观察阿霉素递送至癌细胞。细胞内药物积累分析证实，rHDL/阿霉素纳米载体的治疗导致细胞内阿霉素浓度升高，超过游离药物的水平。在高效药物递送的前提下，rHDL/阿霉素纳米载体已初步证明对两种细胞系在体外均具有有效的细胞毒性作用和细胞凋亡诱导作用。组织分布实验表明，rHDL/阿霉素纳米载体也可以有效地将阿霉素递送至肝脏。因此，我们提出基于这种脂蛋白的策略为治疗肝癌的化疗药物更安全、更有效的递药提供了希望。
