Piradashvili Keti, Simon Johanna, Paßlick David, Höhner Julian R, Mailänder Volker, Wurm Frederik R, Landfester Katharina
Max-Planck-Institut für Polymerforschung, Ackermannweg 10, Mainz 55128, Germany.
Nanoscale Horiz. 2017 Sep 1;2(5):297-302. doi: 10.1039/c7nh00062f. Epub 2017 Jun 30.
The encapsulation of sensitive drugs into nanocarriers retaining their bioactivity and achieving selective release is a challenging topic in current drug delivery design. Established protocols rely on metal-catalyzed or unspecific reactions to build the (mostly synthetic) vehicles which may inhibit the drug's function. Triggered by light, the mild tetrazole-ene cycloaddition enables us to prepare protein nanocarriers (PNCs) preserving at the same time the bioactivity of the sensitive antitumor and antiviral cargo Resiquimod (R848). This catalyst-free reaction was designed to take place at the interface of aqueous nanodroplets in miniemulsion to produce core-shell PNCs with over 90% encapsulation efficiency and no unwanted drug release over storage for several months. Albumins used herein are major constituents of blood and thus ideal biodegradable natural polymers for the production of such nanocarriers. These protein carriers were taken up by dendritic cells and the intracellular drug release by enzymatic degradation of the protein shell material was proven. Together with the thorough colloidal analysis of the PNCs, their stability in human blood plasma and the detailed protein corona composition, these results underline the high potential of such naturally derived drug delivery vehicles.
将敏感药物封装到纳米载体中，同时保持其生物活性并实现选择性释放，是当前药物递送设计中的一个具有挑战性的课题。已有的方案依赖金属催化或非特异性反应来构建（大多为合成的）载体，这可能会抑制药物的功能。在光的触发下，温和的四唑 - 烯环加成反应使我们能够制备蛋白质纳米载体（PNC），同时保留敏感的抗肿瘤和抗病毒药物瑞喹莫德（R848）的生物活性。这种无催化剂反应设计在微乳液中的水性纳米液滴界面进行，以生产核壳型PNC，其包封效率超过90%，并且在储存数月期间没有不需要的药物释放。本文中使用的白蛋白是血液的主要成分，因此是生产此类纳米载体的理想可生物降解天然聚合物。这些蛋白质载体被树突状细胞摄取，并证明了通过蛋白质外壳材料的酶促降解实现细胞内药物释放。连同对PNC的全面胶体分析、它们在人血浆中的稳定性以及详细的蛋白质冠层组成，这些结果突显了此类天然来源药物递送载体的巨大潜力。
