GIFTs

About

Drug delivery systems (DDS) have been widely studied for delivering therapeutic agents to target sites. Among DDS carriers, liposomes have attracted particular attention. With their ability to encapsulate drugs and biomolecules, they have been used in both DDS and molecular robot construction[1][2].

However, conventional liposome-based DDS relies mainly on sustained release, and spatiotemporal control of timing and order has not been realized. This is a major challenge for applications such as combination therapies[3], where multiple drugs must act coordinately. Thus, liposomes capable of spatiotemporally controlled release are highly desired[4].

Here we propose a molecular robot based on multi-compartment liposomes that can release encapsulated molecules in response to DNA signals. Several inner liposomes are enclosed within a larger outer liposome, and both are equipped with DNA origami nanopores. The nanopores on the inner liposomes are capped with DNA, which retains inner molecules. Upon the addition of a signal DNA, the cap DNA strands are removed, allowing the inner and outer liposomes to dock via nanopores, and release their contents. The process is reversible, as the introduction of other designated DNA strands restore the caps, thereby separating the nanopores and halting the release. In this way, the docking–undocking system driven by strand displacement enables precise and repeatable release in response to specific signals.

Our proposing molecular robot realizes spatiotemporally controlled release. This will be applied not only in therapy but also in orchestrating multi-step reactions and material transport in artificial cell systems.

Reference

[1] D. L. Leserman, J. N. Weinstein, R. Blumenthal, and W. D. Terry, “Increased resistance of actively phagocytic cells to complement-mediated lysis,” Proceedings of the National Academy of Sciences of the United States of America (PNAS), vol. 77, no. 7, pp. 4089–4093, 1980. [Online]. Available: https://doi.org/10.1073/pnas.77.7.4089

[2] F. J. Martin, W. L. Hubbell, and D. Papahadjopoulos, “Immunospecific targeting of liposomes to cells: a novel and efficient method for covalent attachment of antibodies to liposomes,” Biochemistry, vol. 20, no. 14, pp. 4229–4238, 1981. [Online]. Available: https://doi.org/10.1021/bi00517a043

[3] J. M. Lee, et al., “Sequence-specific pharmacokinetic and pharmacodynamic interactions of PARP inhibitors with platinum agents,” Clinical Cancer Research, vol. 23, no. 6, pp. 1397–1405, Mar. 2017.

[4] Y. Liu, Q. Chen, H. Zhang, J. Wang, and Y. Gao, “Innovations in cancer therapy: Endogenous stimuli-responsive liposomal nanocarriers,” Pharmaceutics, vol. 15, no. 5, Art. no. 1465, 2023. [Online]. Available: https://www.mdpi.com/1999-4923/17/2/245

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