No abstract

DNA nanostructures with programmable nanoscale patterns has been achieved in the past decades, and molecular information coding (MIC) on those designed nanostructures has gained increasing attention for information security. However, achieving steganography and cryptography synchronously on DNA nanostructures remains a challenge. Herein, we demonstrated MIC in a reconfigurable DNA origami domino array (DODA), which can reconfigure intrinsic patterns but keep the DODA outline the same for steganography. When a set of keys (DNA strands) are added, the cryptographic data can be translated into visible patterns within DODA. More complex cryptography with the ASCII code within a programmable 6×6 lattice is demonstrated to demosntrate the versatility of MIC in the DODA. Furthermore, an anti‐counterfeiting approach based on conformational transformation‐mediated toehold strand displacement reaction is designed to protect MIC from decoding and falsification.

Schematic representation of designed DNA nanostructure grafted with erlotinib and enhanced inhibition of tumor growth for non-small-cell lung cancer (NSCLC).

Molecular patterns with nanoscale precision have been used to mimic complex molecular networks. One key challenge in molecular patterns is to perform active pattern operations in controllable systems to fully imitate their complex dynamic behaviors. Here, we present a reconfigurable DNA origami domino array-based dynamic pattern operation (DODA DPO) system to perform proximity-induced molecular control for complex pattern operations. The activatable platform of reconfigurable DODA endows a spontaneous cascade of stacking conformational transformation from the “before” to the “after” conformation by a set of “trigger” DNA strands. The conformational transformation further brings the operational pattern units into close proximity to undergo DNA strand displacement cascades to accomplish three different pattern operations of “writing”, “erasing”, and “shifting”. Our results also demonstrate the reconfigurable DODA DPO system provides a useful basis to study various molecular control analysis in a fully programmable and controllable fashion.

interact with nuclear DNA and form intraor interstrand crosslinks, thus elicit DNA replication inhibition and cell death. [3,4] However, platinum-based therapy has some disadvantages, such as severe side effects (nephrotoxicity, ototoxicity, and neurotoxicity) and easily acquired drug resistance. [5,6] Though the mechanism of cisplatin resistance is reported to be multifactorial, reduced intracellular cisplatin accumulation is supposed to be the major reason. [7,8] Compared with Pt(II) species, Pt(IV) prodrugs are more inert and more stable in biological environment, thus avoid deactivation by proteins or other biomolecules and reduce side effects. Pt(IV) complexes are reduced more likely in reductive tumor environment to yield cytotoxic Pt(II) drugs. [9-11] Thus, Pt(IV) prodrugs are ideal alternatives to the existing Pt(II) drugs. With the rapid development of nanotechnology, nanoscale drug delivery systems (DDSs) have become an important field of medical research. DDSs have been reported to be a promising strategy to overcome problems associated with platinum-based treatment because of their more active cellular uptake and more accurate tumor localization. [12,13] Nowadays, a variety of DDS have been developed for Pt(IV) prodrug delivery, [14] including gold nanoparticles, [15,16] mesoporous silica nanoparticles, [17,18] carbon nanotubes, [19,20] and so on. [21-23] In recent years, DNA nanostructures have been developed to be a promising candidate for anticancer drug delivery. [24] Compared with traditional inorganic and organic nano particles, DNA nanostructures have many advantages, such as wellcontrolled structure, addressable modification sites, and good biocompatibility. [25-29] By covalently or noncovalently loading, a variety of DNA nanoplatforms have been reported to be effective carriers for small molecular drugs, [30-34] gene therapeutic agents, [35-37] and proteins. [38-40] In particular, a DNA-icosahedron was reported to precisely deliver platinum nanodrugs to cisplatin-resistant cancer, [41] and a DNA tetrahedron was constructed for targeted delivery of the platinum drug 56MESS (a Pt(II)-based DNA intercalator). [42] But so far, to our best knowledge, DNA nanostructures for Pt(IV) prodrug delivery have not been reported. Herein, we constructed three DNA nanostructures with varied sizes and shapes and studied their potential as Pt(IV) Cisplatin is a first-line drug in clinical cancer treatment but its efficacy is often hindered by chemoresistance in cancer cells. Reduced intracellular drug accumulation is revealed to be a major mechanism of cisplatin resistance. Nanoscale drug delivery systems could help to overcome this problem because of their more active cellular uptake and more accurate tumor localization. DNA nanostructures have emerged as promising drug delivery systems because of their intrinsic biocompatibility and structural programmability. Herein, three diverse DNA nanostructures are constructed and their potential for cisplatin prodrug delivery is investigated. Results found that these D...