Theranostics is a technology that integrates diagnostic and therapeutic functions within a single carrier, enabling personalized treatment of tumors. Lipid vesicle-based molecular robots provide a suitable platform to realize this integration in a controllable microscale setting because they combine a sensor, information processing, and an actuator within one system and are being explored for biomedical applications. For the information processing, DNA computing is attracting attention due to the high biocompatibility of DNA molecules. Here, we describe a theranostics molecular robot, TheraLipo, which integrates molecular diagnosis and drug synthesis within a single liposome. TheraLipo was designed for small-cell lung cancer by enabling autonomous detection of the biomarker miR-20a and simultaneous synthesis of the antisense oligonucleotide Oblimersen to induce apoptosis. The body of TheraLipo is a giant unilamellar vesicle (GUV) composed of a lipid bilayer capable of encapsulating reaction components. To transport miR-20 into GUVs, we reconstituted a pore-forming protein streptolysin-O (SLO) in the GUV membrane. For Oblimersen synthesis, we encapsulated an isothermal DNA computing reaction inside GUVs. The reaction consisted of a primer, three templates, and amplification enzyme, and miR-20a triggered the Oblimersen synthesis. To evaluate the theranostic system, we co-encapsulated a molecular beacon that fluoresces specifically upon detecting Oblimersen. When miR-20a was present inside the GUV, miR-20a-specific Oblimersen synthesis continued for at least 3 h. We also observed increased fluorescence when miR-20a was present in the outer solution of TheraLipo, indicating that miR-20a was transported into TheraLipo and that the DNA system synthesized Oblimersen. These results show that TheraLipo provides a unified platform that integrates molecular diagnosis with targeted therapy. As a next step, we will evaluate its activity in Hela cells.
Takeuchi et al. (Sun,) studied this question.