Wongpinyochit Thidarat, Uhlmann Petra, Urquhart Andrew J, Seib F Philipp
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , 161 Cathedral Street, Glasgow, G4 0RE, United Kingdom.
Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Strasse 6, 01069 Dresden, Germany.
Biomacromolecules. 2015 Nov 9;16(11):3712-22. doi: 10.1021/acs.biomac.5b01003. Epub 2015 Oct 13.
Silk has a robust clinical track record and is emerging as a promising biopolymer for drug delivery, including its use as nanomedicine. However, silk-based nanomedicines still require further refinements for full exploitation of their potential; the application of "stealth" design principals is especially necessary to support their evolution. The aim of this study was to develop and examine the potential of PEGylated silk nanoparticles as an anticancer drug delivery system. We first generated B. mori derived silk nanoparticles by driving β-sheet assembly (size 104 ± 1.7 nm, zeta potential -56 ± 5.6 mV) using nanoprecipitation. We then surface grafted polyethylene glycol (PEG) to the fabricated silk nanoparticles and verified the aqueous stability and morphology of the resulting PEGylated silk nanoparticles. We assessed the drug loading and release behavior of these nanoparticles using clinically established and emerging anticancer drugs. Overall, PEGylated silk nanoparticles showed high encapsulation efficiency (>93%) and a pH-dependent release over 14 days. Finally, we demonstrated significant cytotoxicity of drug loaded silk nanoparticles applied as single and combination nanomedicines to human breast cancer cells. In conclusion, these results, taken together with prior silk nanoparticle data, support a viable future for silk-based nanomedicines.
丝绸有着可靠的临床应用记录，并且正成为一种用于药物递送的、颇具前景的生物聚合物，包括用作纳米药物。然而，基于丝绸的纳米药物仍需进一步优化，以充分发挥其潜力；应用“隐形”设计原则对于推动其发展尤为必要。本研究的目的是开发并检验聚乙二醇化丝绸纳米颗粒作为抗癌药物递送系统的潜力。我们首先通过纳米沉淀法驱动β-折叠组装（尺寸为104±1.7纳米，zeta电位为-56±5.6毫伏）生成了家蚕来源的丝绸纳米颗粒。然后我们将聚乙二醇（PEG）表面接枝到制备好的丝绸纳米颗粒上，并验证了所得聚乙二醇化丝绸纳米颗粒的水稳定性和形态。我们使用临床常用的和新出现的抗癌药物评估了这些纳米颗粒的载药和释药行为。总体而言，聚乙二醇化丝绸纳米颗粒显示出高包封率（>93%）以及在14天内的pH依赖性释放。最后，我们证明了作为单一纳米药物和联合纳米药物应用的载药丝绸纳米颗粒对人乳腺癌细胞具有显著的细胞毒性。总之，这些结果与先前的丝绸纳米颗粒数据一起，为基于丝绸的纳米药物的可行未来提供了支持。
