Nucleic Acid-Gated Covalent Organic Frameworks for Cancer-Specific Imaging and Drug Release

Abstract

Developing nanoplatforms that simultaneously integrate diagnostic imaging and therapy functions has been a promising but challenging task for cancer theranostics. Herein, we report the rational design of a smart nucleic acid-gated covalent organic framework (COF) nanosystem for cancer-specific imaging and microenvironment-responsive drug release. Cy5 dye-labeled single-stranded DNA (ssDNA) for mRNA recognition was adsorbed on the surface of doxorubicin (Dox)-loaded COF nanoparticles (NPs). Dox loaded in the pores of COF NPs could strengthen the interactions between ssDNA and COF and enhance the fluorescence quenching effect toward Cy5, while the densely coated ssDNA could prevent the leakage of Dox from COF NPs. The obtained nanosystem exhibited low fluorescence signal and Dox release in normal cells; however, the ssDNA could be released by the overexpressed TK1 mRNA in cancer cells to recover the intense fluorescence signal of Cy5, and the loaded Dox could be further released for chemotherapy. Therefore, cancer cell-specific diagnostic imaging and drug release were realized with the rationally developed nanosystem. This work offers a universal nanoplatform for cancer theranostics and a promising strategy for regulating the interaction between COFs and biomolecules.

Covalent Organic Frameworks (COFs): A Necessary Choice For Drug Delivery

“…A porphyrin COF NPs were prepared by Schiff-based reaction of 5,10,15,20-tetrakis(4aminophenyl)-21H,23H-porphine (Tph) and 2,5-dihydroxyterephthalaldehyde (Dha) by Tang and co-workers. [77] Dox-TpDh NPs enhanced the interaction between TpDh NPs and ssDNA and effectively quenched the Cy5 fluorescence, while the densely coated DNA restrained the non-specific release of Dox from TpDh NPs. In the tumor, the fluorescence of Cy5 was restored due to duplex formation between TK1 mRNA and ssDNA and thus Dox could be released by the acidic microenvironment of the tumor cells.…”

“…A smart nucleic acid‐gated COF nanosystem was designed and constructed successfully for cancer‐specific imaging and microenvironment‐responsive drug release. A porphyrin COF NPs were prepared by Schiff‐based reaction of 5,10,15,20‐tetrakis(4‐aminophenyl)‐21H,23H‐porphine (Tph) and 2,5‐dihydroxyterephthalaldehyde (Dha) by Tang and co‐workers [77] . Dox‐TpDh NPs enhanced the interaction between TpDh NPs and ssDNA and effectively quenched the Cy5 fluorescence, while the densely coated DNA restrained the non‐specific release of Dox from TpDh NPs.…”

Multicolor Covalent Organic Framework–DNA Nanoprobe for Fluorescence Imaging of Biomarkers with Different Locations in Living Cells

“…56,57 Despite several groups including ours having developed some COF-based nanoprobes, the application of COFs for multicolor fluorescence analysis has not been well studied. 29,32,42,44 It is highly desirable to invest more efforts in exploring the potential bioanalytical applications of COFs. Herein, we report the rational design of a COF-based tricolor fluorescent nanoprobe (COF@survivin/MUC1) and its application in simultaneous imaging of biomarkers with different distributions in living cells (Scheme 1).…”

“…Covalent organic frameworks (COFs) have increasingly been employed for bioanalysis and nanomedicine over the past several years. − Owing to their well-defined pore structures and ultrahigh surface areas, COFs can be employed as drug carriers, , while integration of other functional building blocks into the framework structures further endows COFs with other bioactivities. , Therefore, COFs for cancer chemotherapy, photodynamic therapy, photothermal therapy, immune therapy, and combination therapy have been reported. − In addition, COFs have been employed for mass spectrometry, surface-enhanced Raman spectroscopy (SERS), electrochemical analysis, and fluorescence analysis because of their tailored chemical structures and functions. − …”

“…The extended long-range ordered structures of many COFs endow them with forceful broad-spectrum light absorption capacity, indicating that they may serve as promising acceptors to harvest and quench the fluorescence of diverse dyes. ,, Thus, COFs could be readily employed for the design of “turn on” nanoprobes for bioanalysis. Importantly, many COFs with intrinsic fluorescence can be employed for real-time tracing of the distribution of the nanoprobes, which is highly important for precise analysis, especially in the biomedical field. , Despite several groups including ours having developed some COF-based nanoprobes, the application of COFs for multicolor fluorescence analysis has not been well studied. ,,, It is highly desirable to invest more efforts in exploring the potential bioanalytical applications of COFs.…”