Interdepartmental Laboratory of Nanomedicine (NanoMedLab), Laboratory of Supramolecular and BioNano Materials (SupraBioNanoLab), and Fondazione Centro Europeo Nanomedicina (CEN), Department of Chemistry, Materials, and Chemical Engineering "Giulio Natta", Politecnico di Milano , via L. Mancinelli 7, 20131 Milan, Italy.
IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri" , 20156 Milano, Italy.
ACS Nano. 2017 Sep 26;11(9):9413-9423. doi: 10.1021/acsnano.7b04979. Epub 2017 Aug 17.
One of the main hurdles in nanomedicine is the low stability of drug-nanocarrier complexes as well as the drug delivery efficiency in the region-of-interest. Here, we describe the use of the film-forming protein hydrophobin HFBII to organize dodecanethiol-protected gold nanoparticles (NPs) into well-defined supraparticles (SPs). The obtained SPs are exceptionally stable in vivo and efficiently encapsulate hydrophobic drug molecules. The HFBII film prevents massive release of the encapsulated drug, which, instead, is activated by selective SP disassembly triggered intracellularly by glutathione reduction of the protein film. As a consequence, the therapeutic efficiency of an encapsulated anticancer drug is highly enhanced (2 orders of magnitude decrease in IC). Biodistribution and pharmacokinetics studies demonstrate the high stability of the loaded SPs in the bloodstream and the selective release of the payloads once taken up in the tissues. Overall, our results provide a rationale for the development of bioreducible and multifunctional nanomedicines.
纳米医学的主要障碍之一是药物-纳米载体复合物的稳定性低，以及在目标区域的药物输送效率低。在这里，我们描述了使用成膜蛋白 HFBII 将十二硫醇保护的金纳米粒子（NPs）组织成明确定义的超粒子（SPs）。所得到的 SPs 在体内非常稳定，并能有效地封装疏水性药物分子。HFBII 膜防止包封药物的大量释放，而是通过由蛋白质膜内谷胱甘肽还原触发的细胞内选择性 SP 解组装来激活药物释放。因此，封装抗癌药物的治疗效率大大提高（IC 降低 2 个数量级）。生物分布和药代动力学研究表明，负载的 SPs 在血液中的稳定性高，一旦在组织中摄取，就会选择性地释放有效载荷。总的来说，我们的研究结果为开发具有生物还原性和多功能的纳米药物提供了依据。
