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.

中文翻译：

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正交光点击四唑-烯化学可完全降解的蛋白质纳米载体，用于包封和释放†

在当前的药物递送设计中，将敏感药物封装到纳米载体中以保持其生物活性并实现选择性释放是一个具有挑战性的话题。既定的方案依赖于金属催化的或非特异性反应来构建可能抑制药物功能的（大部分为合成的）载体。在光的作用下，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药和抗病毒药物瑞西奎德（R848）的生物活性。这种无催化剂的反应被设计为以细乳液的形式在含水纳米液滴的界面发生，以产生核壳型PNC，其包封效率超过90％，并且在储存几个月后不会释放出不需要的药物。本文使用的白蛋白是血液的主要成分，因此是用于生产此类纳米载体的理想的可生物降解的天然聚合物。这些蛋白质载体被树突状细胞吸收，并且证明了通过蛋白质壳材料的酶促降解释放细胞内药物。连同对PNC的彻底胶体分析，它们在人血浆中的稳定性以及详细的蛋白质电晕成分一起，这些结果突显了这种天然来源的药物递送载体的巨大潜力。