Rossetti Marianna, Ranallo Simona, Idili Andrea, Palleschi Giuseppe, Porchetta Alessandro, Ricci Francesco
Chemistry Department , University of Rome Tor Vergata , Via della Ricerca Scientifica , Rome 00133 , Italy . Email:
Chem Sci. 2017 Feb 1;8(2):914-920. doi: 10.1039/c6sc03404g. Epub 2016 Nov 3.
Here we demonstrate the rational design of a new class of DNA-based nanoswitches which are allosterically regulated by specific biological targets, antibodies and transcription factors, and are able to load and release a molecular cargo ( doxorubicin) in a controlled fashion. In our first model system we rationally designed a stem-loop DNA-nanoswitch that adopts two mutually exclusive conformations: a "Load" conformation containing a doxorubicin-intercalating domain and a "Release" conformation containing a duplex portion recognized by a specific transcription-factor (here Tata Binding Protein). The binding of the transcription factor pushes this conformational equilibrium towards the "Release" state thus leading to doxorubicin release from the nanoswitch. In our second model system we designed a similar stem-loop DNA-nanoswitch for which conformational change and subsequent doxorubicin release can be triggered by a specific antibody. Our approach augments the current tool kit of smart drug release mechanisms regulated by different biological inputs.
在此，我们展示了一类新型基于DNA的纳米开关的合理设计，这些纳米开关由特定生物靶点、抗体和转录因子进行变构调节，并能够以可控方式装载和释放分子货物（阿霉素）。在我们的第一个模型系统中，我们合理设计了一种茎环DNA纳米开关，它采用两种相互排斥的构象：一种是包含阿霉素嵌入结构域的“装载”构象，另一种是包含被特定转录因子（此处为Tata结合蛋白）识别的双链部分的“释放”构象。转录因子的结合将这种构象平衡推向“释放”状态，从而导致阿霉素从纳米开关中释放。在我们的第二个模型系统中，我们设计了一种类似的茎环DNA纳米开关，其构象变化及随后的阿霉素释放可由特定抗体触发。我们的方法扩充了当前由不同生物输入调节的智能药物释放机制的工具包。
