Tetrahedral DNA nanocages as delivery agent for biological and biomedical applications
Abstract
Tetrahedral DNA nanocages have emerged as highly versatile tools for delivering a wide range of biological agents by leveraging their unique structural properties and functional adaptability. This review critically examines the field of tetrahedral DNA nanocages as delivery agents, communicating key findings and insights from existing literature. An extensive examination of the advantages of tetrahedral DNA nanocages as drug-delivery vehicles is outlined, with specific emphasis on their exceptional cargo encapsulation efficiency and controlled release capabilities. An in-depth exploration of in vivo studies and preclinical models is provided, encompassing comprehensive assessments of therapeutic efficacy, pharmacokinetics, toxicity, safety, and targeting capabilities. Moreover, the potential of tetrahedral DNA nanocages in regenerative medicine applications is highlighted. To address future challenges and directions in the field, the review emphasizes the importance of optimization of large-scale synthesis and translational studies. The significant role of tetrahedral DNA nanocages as delivery agents is underscored, showcasing their potential to revolutionize the landscape of targeted and programmable therapeutic interventions.
References
Seeman NC, Sleiman HF. DNA nanotechnology. Nature Reviews Materials 2017; 3(1): 17068(2018). doi: 10.1038/natrevmats.2017.68
Rothemund PWK, Ekani-Nkodo A, Papadakis N, et al. Design and Characterization of Programmable DNA Nanotubes. Journal of the American Chemical Society 2004; 126(50): 16344-16352. doi: 10.1021/ja044319l
Andersen ES, Dong M, Nielsen MM, et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 2009; 459: 73-76. doi: 10.1038/nature07971
Zhang T, Tian T, Zhou R, et al. Design, fabrication, and applications of tetrahedral DNA nanostructure-based multifunctional complexes in drug delivery and biomedical treatment. Nature Protocols 2020, 15: 2728-2757. doi: 10.1038/s41596-020-0355-z
Rajwar A, Vaswani P, Naveena AH, Bhatia D. Chapter. 40 - Designer 3D-DNA nanodevices: Structures, functions, and cellular applications. In: Tripathi T, Dubey VK. Advances in Protein Molecular and Structural Biology Methods. Academic Press; 2022. pp. 669–676.
Schirrmacher V. From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review). International Journal of Oncology 2019; 54(2): 407-419. doi: 10.3892/ijo.2018.4661
Raniolo S, Vindigni G, Ottaviani A, et al. Selective targeting and degradation of doxorubicin-loaded folate-functionalized DNA nanocages. Nanomedicine: Nanotechnology, Biology and Medicine 2018; 14(4) 1181-1190. doi: 10.1016/j.nano.2018.02.002
Huang R, He N, Li Z. Recent progress in DNA nanostructure-based biosensors for detection of tumor markers. Biosensors and Bioelectronics 2018; 109: 27-34. doi: 10.1016/j.bios.2018.02.053
Rajwar A, Shetty SR, Vaswani P, et al. Geometry of a DNA Nanostructure Influences Its Endocytosis: Cellular Study on 2D, 3D, and in Vivo Systems. ACS Nano 2022, 16(7): 10496-10508. doi: 10.1021/acsnano.2c01382
Ma W, Shao X, Zhao D, et al. Self-Assembled Tetrahedral DNA Nanostructures Promote Neural Stem Cell Proliferation and Neuronal Differentiation. ACS Applied Materials & Interfaces 2018; 10(9): 7892-7900. doi: 10.1021/acsami.8b00833
Xie X, Zhang Y, Ma W, et al. Potent anti-angiogenesis and anti-tumor activity of pegaptanib-loaded tetrahedral DNA nanostructure. Cell Proliferation 2019; 52(5): e12662. doi: 10.1111/cpr.12662
Hong S, Jiang W, Ding Q, K, et al. The Current Progress of Tetrahedral DNA Nanostructure for Antibacterial Application and Bone Tissue Regeneration. International Journal of Nanomedicine 2023; 18: 3761-3780. doi: 10.2147/ijn.s403882
Tian T, Zhang T, Shi S, et al. A dynamic DNA tetrahedron framework for active targeting. Nature Protocols 2023; 18: 1028-1055. doi: 10.1038/s41596-022-00791-7
Goodman RP, Berry RM, Turberfield AJ. The single-step synthesis of a DNA tetrahedron. Chemical Communications 2004; 12: 1372-1373 doi: 10.1039/b402293a
Singh R, Yadav P, AHN, Bhatia D. Cationic lipid modification of DNA tetrahedral nanocages enhance their cellular uptake. Nanoscale 2023; 15: 1099-1108. doi: 10.1039/D2NR05749B
Goodman R, Heilemann M, Doose S, et al. Reconfigurable, braced, three-dimensional DNA nanostructures. Nature Nanotechnology 2008; 3: 93-96. doi: 10.1038/nnano.2008.3
Huo S, Kwak M, Qin J, et al. Dynamic DNA-based biomaterials interacting with external, macroscopic, and molecular stimuli. Materials Today 2021; 49: 378-390. doi: 10.1016/j.mattod.2021.04.010
Liu Z, Li Y, Tian C, Mao C. A Smart DNA Tetrahedron That Isothermally Assembles or Dissociates in Response to the Solution pH Value Changes. Biomacromolecules 2013; 14(6): 1711-1714. doi: 10.1021/bm400426f
Ke Y, Bellot G, Voigt NV, et al. Two design strategies for enhancement of multilayer–DNA-origami folding: underwinding for specific intercalator rescue and staple-break positioning. Chemical Science 2012; 3: 2587-2597. doi: 10.1039/C2SC20446K
Gada AR, Vaswani P, Singh R, Bhatia D. Self‐Assembled DNA Nanocages Promote Cell Migration and Differentiation of Human Umbilical Vein Endothelial Cells. ChemBioChem 2023; 24(7): e202200634, doi: 10.1002/cbic.202200634
Han X, Jiang Y, Li S, et al. Multivalent aptamer-modified tetrahedral DNA nanocage demonstrates high selectivity and safety for anti-tumor therapy. Nanoscale 2019; 11: 339-347. doi: 10.1039/C8NR05546G
Han X, Xu X, Wu Z, et al. Synchronous conjugation of i-motif DNA and therapeutic siRNA on the vertexes of tetrahedral DNA nanocages for efficient gene silence. Acta Pharmaceutica Sinica B 2021; 11(10): 3286-3296. doi: 10.1016/j.apsb.2021.02.009
Zhang T, Tian T, Lin Y. Functionalizing Framework Nucleic‐Acid‐Based Nanostructures for Biomedical Application. Advanced Materials 2022; 34(46): 2107820. doi: 10.1002/adma.202107820
Xia Z, Wang P, Liu X, et al. Tumor-penetrating peptide-modified DNA tetrahedron for targeting drug delivery. Biochemistry 2016; 55(9): 1326-1331. doi: 10.1021/acs.biochem.5b01181
Rosier BJHM, Cremers GAO, Engelen W, et al. Incorporation of native antibodies and Fc-fusion proteins on DNA nanostructures via a modular conjugation strategy. Chemical Communications 2017; 53: 7393-7396. doi: 10.1039/c7cc04178k
Ma W, Zhan Y, Zhang Y, et al. The biological applications of DNA nanomaterials: current challenges and future directions. Signal Transduction and Targeted Therapy 2021; 6:351. doi: 10.1038/s41392-021-00727-9
Hu W, Zhang J, Kong J. Fluorescence Detection of DNA Based on Non-covalent π-π Stacking Interaction between 1-Pyrenebutanoic Acid and Hypericin. Analytical Sciences 2016; 32(5): 523-527. doi: 10.2116/analsci.32.523
Chandrasekaran AR, Levchenko O. DNA Nanocages. Chemistry of Materials 2016; 28(16) :5569-5581. doi: 10.1021/acs.chemmater.6b02546
Crawford R, Erben CM, Periz J, et al. Non-covalent Single Transcription Factor Encapsulation Inside a DNA Cage. Angewandte Chemie International Edition version 2013; 52(8): 2284-2288. doi: 10.1002/anie.201207914
Cremers GAO, Rosier BJHM, Meijs A, et al. Determinants of Ligand-Functionalized DNA Nanostructure-Cell Interactions. Journal of the American Chemical Society 2021; 143(27): 10131-10142. doi: 10.1021/jacs.1c02298
Liu X, Xu Y, Yu T, et al. A DNA Nanostructure Platform for Directed Assembly of Synthetic Vaccines. Nano Letters 2012; 12(8): 4254-4259. doi: 10.1021/nl301877k
Zhou M, Gao S, Zhang X, et al. The protective effect of tetrahedral framework nucleic acids on periodontium under inflammatory conditions. Bioactive Materials 2021; 6(6): 1676-1688. doi: 10.1016/j.bioactmat.2020.11.018
Li D, Yang Z, Luo Y, et al. Delivery of MiR335‐5p‐Pendant Tetrahedron DNA Nanostructures Using an Injectable Heparin Lithium Hydrogel for Challenging Bone Defects in Steroid‐Associated Osteonecrosis. Advanced Healthcare Materials 2022; 11(1): 2101412. doi: 10.1002/adhm.202101412
Lin Y, Li Q, Wang L, et al. Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation. International Journal of Oral Science 2022; 14: 51. doi: 10.1038/s41368-022-00199-9
Bhaskar S, Lim S. Engineering protein nanocages as carriers for biomedical applications. NPG Asia Materials 2017; 9: e371. doi: 10.1038/am.2016.128
Grossi G, Jaekel A, Andersen ES, Saccà B. Enzyme-functionalized DNA nanostructures as tools for organizing and controlling enzymatic reactions. MRS Bulletin 2017; 42(12): 920-924. doi: 10.1557/mrs.2017.269
Wamhoff EC, Knappe GA, Burds AA, et al. Evaluation of Nonmodified Wireframe DNA Origami for Acute Toxicity and Biodistribution in Mice. ACS Applied Bio Materials 2023; 6(5):1960-1969. doi: 10.1021/acsabm.3c00155
Xu Y, Huang SW, Ma YQ, Ding HM. Loading of DOX into a tetrahedral DNA nanostructure: the corner does matter. Nanoscale Advances 2022; 4:754-760. doi: 10.1039/d1na00753j
Liu J, Song L, Liu S, et al. A Tailored DNA nano platform for Synergistic RNAi-/Chemotherapy of Multidrug-Resistant Tumors. Angewandte Chemie International Edition 2018; 57(47): 15486-15490. doi: 10.1002/anie.201809452
Zhang X, Li X, Wang D, et al. Spectroscopic, calorimetric and cytotoxicity studies on the combined binding of daunorubicin and acridine orange to a DNA tetrahedron. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2023; 295: 122583. doi: 10.1016/j.saa.2023.122583
Zhang M, Zhang X, Tian T, et al. Anti-inflammatory activity of curcumin-loaded tetrahedral framework nucleic acids on acute gouty arthritis. Bioactive Materials 2022; 8: 368-380. doi: 10.1016/j.bioactmat.2021.06.003
Yang J, Jiang Q, He L, et al. Self-Assembled Double-Bundle DNA Tetrahedron for Efficient Antisense Delivery. ACS Applied Materials & Interfaces 2018; 10(28): 23693-23699. doi: 10.1021/acsami.8b07889
Lee H, Lytton-Jean AKL, Chen Y, et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nature Nanotechnology 2012; 7: 389-393. doi: 10.1038/nnano.2012.73
Jiang D, Sun Y, Li J, et al. Multiple-Armed Tetrahedral DNA Nanostructures for Tumor-Targeting, Dual-Modality in Vivo Imaging. ACS Applied Materials & Interfaces 2016; 8(7): 4378-4384. doi: 10.1021/acsami.5b10792
Okholm AH, Kjems J. The utility of DNA nanostructures for drug delivery in vivo. Expert Opinion on Drug Delivery 2017; 14(2): 137-139. doi: 10.1080/17425247.2017.1266335
Jorge AF, Aviñó A, Pais AACC, et al. DNA-based nanoscaffolds as vehicles for 5-fluoro-2′-deoxyuridine oligomers in colorectal cancer therapy. Nanoscale 2018; 10:7238-7249. doi: 10.1039/c7nr08442k
Tian T, Li J, Xie C, et al. Targeted Imaging of Brain Tumors with a Framework Nucleic Acid Probe. ACS Applied Materials & Interfaces 2018; 10(4): 3414-3420. doi: 10.1021/acsami.7b17927
Sui L, Wang M, Han Q, et al. A novel Lipidoid-MicroRNA formulation promotes calvarial bone regeneration. Biomaterials 2018; 177: 88-97. doi: 10.1016/j.biomaterials.2018.05.038
Zhang H, Wu S, Chen W, et al. Bone/cartilage targeted hydrogel: Strategies and applications. Bioactive Materials 2023; 23: 156-169. doi: 10.1016/j.bioactmat.2022.10.028
Zhao D, Liu M, Li J, et al. Angiogenic Aptamer-Modified Tetrahedral Framework Nucleic Acid Promotes Angiogenesis In Vitro and In Vivo. ACS Applied Materials & Interfaces 2021; 13(25): 29439-29449. doi: 10.1021/acsami.1c08565
Zhang T, Cui W, Tian T, et al. Progress in Biomedical Applications of Tetrahedral Framework Nucleic Acid-Based Functional Systems. ACS Applied Materials & Interfaces 2020; 12(42): 47115-47126. doi: 10.1021/acsami.0c13806.
Kansara K, Mansuri A, Rajwar A, et al. Spatiotemporal dynamics of DNA nanocage uptake in zebrafish embryos for targeted tissue bioimaging applications. Nanoscale Advances 2023; 5: 2558-2564. doi: 10.1039/d2na00905f
Dou Y, Cui W, Yang X, et al. Applications of tetrahedral DNA nanostructures in wound repair and tissue regeneration. Burns Trauma 2022; 10: tkac006. doi: 10.1093/burnt/tkac006
Zeng Y, Chang P, Ma J, et al. DNA Origami–Anthraquinone Hybrid Nanostructures for In Vivo Quantitative Monitoring of the Progression of Tumor Hypoxia Affected by Chemotherapy. ACS Applied Materials & Interfaces 2022; 14(5): 6387-6403. doi: 10.1021/acsami.1c22620
Zhao N, Pei SN, Qi J, et al. Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid leukemia. Biomaterials 2015; 67: 42-51. doi: 10.1016/j.biomaterials.2015.07.025
Pan G, Mou Q, Ma Y, et al. pH-Responsive and Gemcitabine-Containing DNA Nanogel To Facilitate the Chemodrug Delivery. ACS Applied Materials & Interfaces 2019; 11(44): 41082-41090. doi: 10.1021/acsami.9b14892
Park JY, Cho YL, Chae JR, et al. Gemcitabine-Incorporated G-Quadruplex Aptamer for Targeted Drug Delivery into Pancreas Cancer. Molecular Therapy Nucleic Acids 2018; 12: 543-553. doi: 10.1016/j.omtn.2018.06.003
Lin L, Fan Y, Gao F, et al. UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy. Theranostics 2018; 8(7): 1923-1939. doi: 10.7150/thno.22834
Anwar DM, El-Sayed M, Reda A, et al. Recent advances in herbal combination nanomedicine for cancer: delivery technology and therapeutic outcomes. Expert Opinion on Drug Delivery 2021; 18(11): 1609-1625. doi: 10.1080/17425247.2021.1955853
Wang F, Bronich TK, Kabanov AV, et al. Synthesis and Characterization of Star Poly(ε-caprolactone)-b-Poly(ethylene glycol) and Poly(l-lactide)-b-Poly(ethylene glycol) Copolymers: Evaluation as Drug Delivery Carriers. Bioconjugate Chemistry 2008; 19(7): 1423-1429. doi: 10.1021/bc7004285
Yu Z, Li X, Duan J, Yang XD. Targeted Treatment of Colon Cancer with Aptamer-Guided Albumin Nanoparticles Loaded with Docetaxel. International Journal of Nanomedicine 2020; 15: 6737-6748. doi: 10.2147/ijn.s267177
Bannister AH, Bromma K, Sung W, et al. Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy. The British Journal of Radiology 2020; 93(1106): 20190742. doi: 10.1259/bjr.20190742
Li X, He M, Zhou Z, et al. The antitumor activity of PNA modified vinblastine cationic liposomes on Lewis lung tumor cells: In vitro and in vivo evaluation. International Journal of Pharmaceutics 2015; 487(1-2): 223-233. doi: 10.1016/j.ijpharm.2015.04.035
H. Maswadeh, S. Hatziantoniou, C. Demetzos, et al. Encapsulation of vinblastine into new liposome formulations prepared from triticum (wheat germ) lipids and its activity against human leukemic cell lines. Available online: http://europepmc.org/abstract/MED/11205276 (accessed on 1 November 2000).
Lu YJ, Chuang EY, Cheng YH, et al. Thermosensitive magnetic liposomes for alternating magnetic field-inducible drug delivery in dual-targeted brain tumor chemotherapy. Chemical Engineering Journal 2019; 373: 720-733. doi: 10.1016/j.cej.2019.05.055
Karimi M, Zangabad PS, Baghaee-Ravari S, et al. Smart Nanostructures for Cargo Delivery: Uncaging and Activating by Light. Journal of the American Chemical Society 2017; 139(13): 4584-4610. doi: 10.1021/jacs.6b08313
Imanparast A, Bakhshizadeh M, Salek R, Sazgarnia A. Pegylated hollow gold-mitoxantrone nanoparticles combining photodynamic therapy and chemotherapy of cancer cells. Photodiagnosis and Photodynamic Therapy 2018; 23:295-305. doi: 10.1016/j.pdpdt.2018.07.011
Hu XY, Jia K, Cao Y, et al. Dual Photo- and pH-Responsive Supramolecular Nanocarriers Based on Water-Soluble Pillar[6]arene and Different Azobenzene Derivatives for Intracellular Anticancer Drug Delivery. Chemistry-A European Journal 2015; 21(3): 1208-1220. doi: 10.1002/chem.201405095
Cai L, Yu R, Hao X, Ding X. Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers. Nanoscale Research Letters 2017; 12(1): 509. doi: 10.1186/s11671-017-2253-z
Zhang H, Liu G, Zeng X, et al. Fabrication of genistein-loaded biodegradable TPGS-b-PCL nanoparticles for improved therapeutic effects in cervical cancer cells. International Journal of Nanomedicine 2015; 10: 2461-2473. doi: 10.2147/ijn.S78988
Juul S, Iacovelli F, Falconi M, et al. Temperature-Controlled Encapsulation and Release of an Active Enzyme in the Cavity of a Self-Assembled DNA Nanocage. ACS Nano 2013; 7(11): 9724-9734. doi: 10.1021/nn4030543
Arnon S, Dahan N, Koren A, et al. Thought-Controlled Nanoscale Robots in a Living Host. PLOS ONE 2016; 11(8): e0161227. doi: 10.1371/journal.pone.0161227
Ko O, Han S, Lee JB. Selective release of DNA nanostructures from DNA hydrogel. Journal of Industrial and Engineering Chemistry 2020; 84: 46-51. doi: https://doi.org/10.1016/j.jiec.2020.01.005
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