DNA nanostructures-based delivery system for cancer immunotherapy
(
)Graphical Abstract
Abstract
Immunotherapy has been emerging as a potent strategy for cancer treatment. However, undesirable therapeutic efficacy remains a challenge, including low drug loading, imprecise targeting, and non-specific releasing. The drug delivery systems of immunotherapy play a key role in improving therapeutic efficacy and reducing side effects. To address these concerns, functional DNA nanostructures-based materials have been explored to achieve high loading capability, precise targeting, and controllable releasing. This review focuses on the crucial issues of delivery system for cancer immunotherapy and the strategies to improve the delivery efficacy. Specifically, recent advances in DNA nanostructures-based materials that promote the therapeutic efficacy of cancer immunotherapy through rational DNA sequence design to regulate the spatial distribution of immunotherapeutics loading are reviewed. The strategies to enhance precise targeting ability basing on nucleic acid aptamers and further enable immune checkpoint inhibitions are presented. The recent progress on the controllable release of immunotherapeutics triggered by specific stimulus is discussed. In the end, we provide insights for the subsequent realization of applications of DNA nanostructures-based materials for cancer immunotherapy in the future.
Keywords
References
Siegel, R. L.; Miller, K. D.; Fuchs, H. E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 2022, 72, 7–33.
Saxena, M.; van der Burg, S. H.; Melief, C. J. M.; Bhardwaj, N. Therapeutic cancer vaccines. Nat. Rev. Cancer 2021, 21, 360–378.
Ott, P. A.; Hu, Z. T.; Keskin, D. B.; Shukla, S. A.; Sun, J.; Bozym, D. J.; Zhang, W. D.; Luoma, A.; Giobbie-Hurder, A.; Peter, L. et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017, 547, 217–221.
Mellman, I.; Coukos, G.; Dranoff, G. Cancer immunotherapy comes of age. Nature 2011, 480, 480–489.
Colley, A.; Brauns, T.; Sluder, A. E.; Poznansky, M. C.; Gemechu, Y. Immunomodulatory drugs: A promising clinical ally for cancer immunotherapy. Trends Mol. Med. 2024, 30, 765–780.
Propper, D. J.; Balkwill, F. R. Harnessing cytokines and chemokines for cancer therapy. Nat. Rev. Clin. Oncol. 2022, 19, 237–253.
Dranoff, G. Cytokines in cancer pathogenesis and cancer therapy. Nat. Rev. Cancer 2004, 4, 11–22.
Sharma, P.; Goswami, S.; Raychaudhuri, D.; Siddiqui, B. A.; Singh, P.; Nagarajan, A.; Liu, J. L.; Subudhi, S. K.; Poon, C.; Gant, K. L. et al. Immune checkpoint therapy-current perspectives and future directions. Cell 2023, 186, 1652–1669.
Peng, L.; Sferruzza, G.; Yang, L. J.; Zhou, L. Q.; Chen, S. D. CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors. Cell. Mol. Immunol. 2024, 21, 1089–1108.
Huang, X.; Williams, J. Z.; Chang, R.; Li, Z. B.; Burnett, C. E.; Hernandez-Lopez, R.; Setiady, I.; Gai, E.; Patterson, D. M.; Yu, W. et al. DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation. Nat. Nanotechnol. 2020, 16, 214–223.
Yang, J. W.; Chen, Y. M.; Jing, Y.; Green, M. R.; Han, L. Advancing CAR T cell therapy through the use of multidimensional omics data. Nat. Rev. Clin. Oncol. 2023, 20, 211–228.
Lin, M. J.; Svensson-Arvelund, J.; Lubitz, G. S.; Marabelle, A.; Melero, I.; Brown, B. D.; Brody, J. D. Cancer vaccines: The next immunotherapy frontier. Nat. Cancer 2022, 3, 911–926.
Riley, R. S.; June, C. H.; Langer, R.; Mitchell, M. J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug Discov. 2019, 18, 175–196.
Banchereau, J.; Palucka, A. K. Dendritic cells as therapeutic vaccines against cancer. Nat. Rev. Immunol. 2005, 5, 296–306.
Zhu, G. Z.; Zhang, F. W.; Ni, Q. Q.; Niu, G.; Chen, X. Y. Efficient nanovaccine delivery in cancer immunotherapy. ACS Nano 2017, 11, 2387–2392.
Karki, R.; Kanneganti, T. D. The ‘cytokine storm’: Molecular mechanisms and therapeutic prospects. Trends Immunol. 2021, 42, 681–705.
Cabral, H.; Li, J. J.; Miyata, K.; Kataoka, K. Controlling the biodistribution and clearance of nanomedicines. Nat. Rev. Bioeng. 2023, 2, 214–232.
Ma, W. J.; Zhan, Y. X.; Zhang, Y. X.; Mao, C. C.; Xie, X. P.; Lin, Y. F. The biological applications of DNA nanomaterials: Current challenges and future directions. Signal Transduct. Target. Ther. 2021, 6, 351.
Lee, H.; Lytton-Jean, A. K. R.; Chen, Y.; Love, K. T.; Park, A. I.; Karagiannis, E. D.; Sehgal, A.; Querbes, W.; Zurenko, C. S.; Jayaraman, M. et al. Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery. Nat. Nanotechnol. 2012, 7, 389–393.
Jani, M. S.; Veetil, A. T.; Krishnan, Y. Precision immunomodulation with synthetic nucleic acid technologies. Nat. Rev. Mater. 2019, 4, 451–458.
Iinuma, R.; Ke, Y. G.; Jungmann, R.; Schlichthaerle, T.; Woehrstein, J. B.; Yin, P. Polyhedra self-assembled from DNA tripods and characterized with 3D DNA-PAINT. Science 2014, 344, 65–69.
Goodman, R. P.; Schaap, I. A. T.; Tardin, C. F.; Erben, C. M.; Berry, R. M.; Schmidt, C. F.; Turberfield, A. J. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 2005, 310, 1661–1665.
Chu, Z. Y.; Wang, W. N.; Zheng, W.; Fu, W. Y.; Wang, Y. J.; Wang, H.; Qian, H. S. Biomaterials with cancer cell-specific cytotoxicity: Challenges and perspectives. Chem. Soc. Rev. 2024, 53, 8847–8877.
Dai, Y. L.; Xu, C.; Sun, X. L.; Chen, X. Y. Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment. Chem. Soc. Rev. 2017, 46, 3830–3852.
Xie, S. T.; Sun, W. D.; Fu, T.; Liu, X. S.; Chen, P.; Qiu, L. P.; Qu, F. L.; Tan, W. H. Aptamer-based targeted delivery of functional nucleic acids. J. Am. Chem. Soc. 2023, 145, 7677–7691.
Li, F.; Song, N. C.; Dong, Y. H.; Li, S.; Li, L. H.; Liu, Y. J.; Li, Z. M.; Yang, D. Y. A proton-activatable DNA-based nanosystem enables co-delivery of CRISPR/Cas9 and DNAzyme for combined gene therapy. Angew. Chem., Int. Ed. 2022, 61, e202116569.
Guo, X. C.; Li, F.; Liu, C. X.; Zhu, Y.; Xiao, N. N.; Gu, Z.; Luo, D.; Jiang, J. H.; Yang, D. Y. Construction of organelle-like architecture by dynamic DNA assembly in living cells. Angew. Chem., Int. Ed. 2020, 59, 20651–20658.
Sun, W. J.; Jiang, T. Y.; Lu, Y.; Reiff, M.; Mo, R.; Gu, Z. Cocoon-like self-degradable DNA nanoclew for anticancer drug delivery. J. Am. Chem. Soc. 2014, 136, 14722–14725.
Li, F.; Liu, Y. J.; Dong, Y. H.; Chu, Y. W.; Song, N. C.; Yang, D. Y. Dynamic assembly of DNA nanostructures in living cells for mitochondrial interference. J. Am. Chem. Soc. 2022, 144, 4667–4677.
Qian, R. C.; Zhou, Z. R.; Guo, W. J.; Wu, Y. T.; Yang, Z. L.; Lu, Y. Cell surface engineering using DNAzymes: Metal ion mediated control of cell-cell interactions. J. Am. Chem. Soc. 2021, 143, 5737–5744.
Lv, Z. Y.; Huang, M. X.; Yang, J.; Li, P. R.; Chang, L. L.; Tang, Q. Y.; Chen, X. J.; Wang, S. Q.; Yao, C.; Liu, P. F. et al. A smart DNA-based nanosystem containing ribosome-regulating siRNA for enhanced mRNA transfection. Adv. Mater. 2023, 35, 2300823.
Li, J.; Zheng, C.; Cansiz, S.; Wu, C. C.; Xu, J. H.; Cui, C.; Liu, Y.; Hou, W. J.; Wang, Y. Y.; Zhang, L. Q. et al. Self-assembly of DNA nanohydrogels with controllable size and stimuli-responsive property for targeted gene regulation therapy. J. Am. Chem. Soc. 2015, 137, 1412–1415.
Wang, Z. R.; Song, L. L.; Liu, Q.; Tian, R.; Shang, Y. X.; Liu, F. S.; Liu, S. L.; Zhao, S.; Han, Z. H.; Sun, J. S. et al. A tubular DNA nanodevice as a siRNA/chemo-drug co-delivery vehicle for combined cancer therapy. Angew. Chem., Int. Ed. 2021, 60, 2594–2598.
Li, Q.; Liu, L. F.; Mao, D. K.; Yu, Y. Y.; Li, W. L.; Zhao, X. F.; Mao, C. D. ATP-triggered, allosteric self-assembly of DNA nanostructures. J. Am. Chem. Soc. 2020, 142, 665–668.
Song, P.; Ye, D. K.; Zuo, X. L.; Li, J.; Wang, J. B.; Liu, H. J.; Hwang, M. T.; Chao, J.; Su, S.; Wang, L. H. et al. DNA hydrogel with aptamer-toehold-based recognition, cloaking, and decloaking of circulating tumor cells for live cell analysis. Nano Lett. 2017, 17, 5193–5198.
Gong, H. S.; Zhang, Y. H.; Xue, Y.; Fang, B. W.; Li, Y. T.; Zhu, X. D.; Du, Y.; Peng, P. NETosis-inspired cell surface-constrained framework nucleic acids traps (FNATs) for cascaded extracellular recognition and cellular behavior modulation. Angew. Chem., Int. Ed. 2024, 63, e202319908.
Wang, J.; Li, Y. Y.; Nie, G. J. Multifunctional biomolecule nanostructures for cancer therapy. Nat. Rev. Mater. 2021, 6, 766–783.
Wang, C.; Sun, W. J.; Wright, G.; Wang, A. Z.; Gu, Z. Inflammation-triggered cancer immunotherapy by programmed delivery of CpG and anti-PD1 antibody. Adv. Mater. 2016, 28, 8912–8920.
Liu, M. T.; Hao, L. Y.; Zhao, D.; Li, J. J.; Lin, Y. F. Self-assembled immunostimulatory tetrahedral framework nucleic acid vehicles for tumor chemo-immunotherapy. ACS Appl. Mater. Interfaces 2022, 14, 38506–38514.
Wu, Y. N.; Li, Q. Y.; Shim, G.; Oh, Y. K. Melanin-loaded CpG DNA hydrogel for modulation of tumor immune microenvironment. J. Control. Release 2021, 330, 540–553.
Yao, C.; Zhu, C. X.; Tang, J. P.; Ou, J. H.; Zhang, R.; Yang, D. Y. T lymphocyte-captured DNA network for localized immunotherapy. J. Am. Chem. Soc. 2021, 143, 19330–19340.
Douglas, S. M.; Bachelet, I.; Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 2012, 335, 831–834.
Jiang, Q.; Liu, S. L.; Liu, J. B.; Wang, Z. G.; Ding, B. Q. Rationally designed DNA-origami nanomaterials for drug delivery in vivo. Adv. Mater. 2019, 31, 1804785.
Xie, Y. X.; Li, H. S.; Xu, L.; Zou, H. B.; Wang, X. G.; He, X. Z.; Tang, Q. Y.; Zhou, Y.; Zhao, X.; Chen, X. J. et al. DNA nanoclusters combined with one-shot radiotherapy augment cancer immunotherapy efficiency. Adv. Mater. 2023, 35, 2208546.
Hopfner, K. P.; Hornung, V. Molecular mechanisms and cellular functions of cGAS-STING signalling. Nat. Rev. Mol. Cell Biol. 2020, 21, 501–521.
Zhang, L. P.; Wang, Y. Q.; Karges, J.; Tang, D. S.; Zhang, H. C.; Zou, K. X.; Song, J.; Xiao, H. H. Tetrahedral DNA nanostructure with interferon stimulatory DNA delivers highly potent toxins and activates the cGAS-STING pathway for robust chemotherapy and immunotherapy. Adv. Mater. 2022, 35, 2210267.
Guo, W. J.; Gao, H. B.; Li, H.; Ge, S. H.; Zhang, F. F.; Wang, L. Y.; Shi, H. J.; Han, A. J. Self-assembly of a multifunction DNA tetrahedron for effective delivery of aptamer PL1 and Pcsk9 siRNA potentiate immune checkpoint therapy for colorectal cancer. ACS Appl. Mater. Interfaces 2022, 14, 31634–31644.
Tan, J.; Li, H.; Hu, X. X.; Abdullah, R.; Xie, S. T.; Zhang, L. L.; Zhao, M. M.; Luo, Q.; Li, Y. Z.; Sun, Z. J. et al. Size-tunable assemblies based on ferrocene-containing DNA polymers for spatially uniform penetration. Chem 2019, 5, 1775–1792.
Fan, D. H.; Cao, Y. K.; Cao, M. Q.; Wang, Y. J.; Cao, Y. L.; Gong, T. Nanomedicine in cancer therapy. Signal Transduct. Target. Ther. 2023, 8, 293.
Rothemund, P. W. K. Folding DNA to create nanoscale shapes and patterns. Nature 2006, 440, 297–302.
Hu, X. X.; Chi, H. L.; Fu, X. Y.; Chen, J. L.; Dong, L. Y.; Jiang, S. Q.; Li, Y. Y.; Chen, J. Y.; Cheng, M.; Min, Q. H. et al. Tunable multivalent aptamer-based DNA nanostructures to regulate multiheteroreceptor-mediated tumor recognition. J. Am. Chem. Soc. 2024, 146, 2514–2523.
Liu, S. L.; Jiang, Q.; Zhao, X.; Zhao, R. F.; Wang, Y. N.; Wang, Y. M.; Liu, J. B.; Shang, Y. X.; Zhao, S.; Wu, T. T. et al. A DNA nanodevice-based vaccine for cancer immunotherapy. Nat. Mater. 2021, 20, 421–430.
Wamhoff, E. C.; Ronsard, L.; Feldman, J.; Knappe, G. A.; Hauser, B. M.; Romanov, A.; Case, J. B.; Sanapala, S.; Lam, E. C.; Denis, K. J. S. et al. Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds. Nat. Commun. 2024, 15, 795.
Sun, Y. Y.; Sun, J. J.; Xiao, M. S.; Lai, W.; Li, L.; Fan, C. H.; Pei, H. DNA origami-based artificial antigen-presenting cells for adoptive T cell therapy. Sci. Adv. 2022, 8, eadd1106.
Teplensky, M. H.; Evangelopoulos, M.; Dittmar, J. W.; Forsyth, C. M.; Sinegra, A. J.; Wang, S. Y.; Mirkin, C. A. Multi-antigen spherical nucleic acid cancer vaccines. Nat. Biomed. Eng. 2023, 7, 911–927.
Sun, L. L.; Shen, F. Y.; Xiong, Z. J.; Chao, Y.; Fan, C. H.; Liu, Z. Nanoscale precise editing of multiple immune stimulating ligands on DNA origami for T cell activation and cell-based cancer immunotherapy. CCS Chem. 2024, 6, 719–732.
Zeng, Y. C.; Young, O. J.; Wintersinger, C. M.; Anastassacos, F. M.; MacDonald, J. I.; Isinelli, G.; Dellacherie, M. O.; Sobral, M.; Bai, H. Q.; Graveline, A. R. et al. Fine tuning of CpG spatial distribution with DNA origami for improved cancer vaccination. Nat. Nanotechnol. 2024, 19, 1055–1065.
Min, H. Y.; Lee, H. Y. Molecular targeted therapy for anticancer treatment. Exp. Mol. Med. 2022, 54, 1670–1694.
Zhou, J. H.; Rossi, J. Aptamers as targeted therapeutics: Current potential and challenges. Nat. Rev. Drug Discov. 2017, 16, 181–202.
Li, L.; Xu, S. J.; Yan, H.; Li, X. W.; Yazd, H. S.; Li, X.; Huang, T.; Cui, C.; Jiang, J. H.; Tan, W. H. Nucleic acid aptamers for molecular diagnostics and therapeutics: Advances and perspectives. Angew. Chem., Int. Ed. 2021, 60, 2221–2231.
Soundararajan, S.; Chen, W. W.; Spicer, E. K.; Courtenay-Luck, N.; Fernandes, D. J. The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer Res. 2008, 68, 2358–2365.
Lv, Z. Y.; Li, Z. M.; Zou, S. L.; Li, P. R.; Song, N. C.; Zhang, R.; Xu, M. D.; Liu, M. X.; Li, F. Q.; Li, J. R. et al. A smart DNA nanoassembly containing multivalent aptamers enables controlled delivery of CRISPR/Cas9 for cancer immunotherapy. Adv. Funct. Mater. 2024, 34, 2311069.
Ali, M. M.; Li, F.; Zhang, Z. Q.; Zhang, K. X.; Kang, D. K.; Ankrum, J. A.; Le, X. C.; Zhao, W. A. Rolling circle amplification: A versatile tool for chemical biology, materials science and medicine. Chem. Soc. Rev. 2014, 43, 3324–3341.
He, X.; Xu, C. Q. Immune checkpoint signaling and cancer immunotherapy. Cell Res. 2020, 30, 660–669.
Sharma, P.; Allison, J. P. The future of immune checkpoint therapy. Science 2015, 348, 56–61.
Sun, Q.; Hong, Z. Y.; Zhang, C.; Wang, L. L.; Han, Z. Q.; Ma, D. Immune checkpoint therapy for solid tumours: Clinical dilemmas and future trends. Signal Transduct. Target. Ther. 2023, 8, 320.
Wolchok, J. D.; Kluger, H.; Callahan, M. K.; Postow, M. A.; Rizvi, N. A.; Lesokhin, A. M.; Segal, N. H.; Ariyan, C. E.; Gordon, R. A.; Reed, K. et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 2013, 369, 122–133.
Guo, M. Y.; Zhang, X.; Liu, J.; Gao, F. N.; Zhang, X. L.; Hu, X. H.; Li, B.; Zhang, X.; Zhou, H. G.; Bai, R. et al. Few-layer bismuthene for checkpoint knockdown enhanced cancer immunotherapy with rapid clearance and sequentially triggered one-for-all strategy. ACS Nano 2020, 14, 15700–15713.
Lu, Q. L.; Chen, R. Y.; Du, S. Y.; Chen, C.; Pan, Y. C.; Luan, X. W.; Yang, J. J.; Zeng, F.; He, B. S.; Han, X. et al. Activation of the cGAS-STING pathway combined with CRISPR-Cas9 gene editing triggering long-term immunotherapy. Biomaterials 2022, 291, 121871.
Cotton, A. D.; Nguyen, D. P.; Gramespacher, J. A.; Seiple, I. B.; Wells, J. A. Development of antibody-based PROTACs for the degradation of the cell-surface immune checkpoint protein PD-L1. J. Am. Chem. Soc. 2021, 143, 593–598.
Su, W.; Tan, M. X.; Wang, Z. H.; Zhang, J.; Huang, W. P.; Song, H. H.; Wang, X. Y.; Ran, H. T.; Gao, Y. F.; Nie, G. J. et al. Targeted degradation of PD-L1 and activation of the STING pathway by carbon-dot-based PROTACs for cancer immunotherapy. Angew. Chem., Int. Ed. 2023, 62, e202218128.
Sun, Y.; Mo, L. T.; Hu, X. X.; Yu, D.; Xie, S. T.; Li, J. L.; Zhao, Z. L.; Fang, X. H.; Ye, M.; Qiu, L. P. et al. Bispecific aptamer-based recognition-then-conjugation strategy for PD1/PDL1 axis blockade and enhanced immunotherapy. ACS Nano 2022, 16, 21129–21138.
Zhang, R.; Lv, Z. Y.; Chang, L. L.; Wang, J.; Tang, J. P.; Wang, Z. Q.; Li, S. Q.; Guo, J. F.; Yao, C.; Yang, D. Y. A responsive DNA hydrogel containing poly-aptamers as dual-target inhibitors for localized cancer immunotherapy. Adv. Funct. Mater. 2024, 34, 2401563.
Li, Y. Q.; Liu, X. L.; Yu, L.; Huang, X.; Wang, X.; Han, D.; Yang, Y.; Liu, Z. Covalent LYTAC enabled by DNA aptamers for immune checkpoint degradation therapy. J. Am. Chem. Soc. 2023, 145, 24506–24521.
Bi, S. Y.; Chen, W.; Fang, Y. Y.; Shen, J. Y.; Zhang, Q.; Guo, H. Q.; Ju, H. X.; Liu, Y. Cancer cell-selective PD-L1 inhibition via a DNA safety catch to enhance immunotherapy specificity. Angew. Chem., Int. Ed. 2024, 63, e202402522.
Shi, J. J.; Kantoff, P. W.; Wooster, R.; Farokhzad, O. C. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer 2017, 17, 20–37.
Hou, J. J.; Zhu, S. T.; Zhao, Z. W.; Shen, J. L.; Chao, J.; Shi, J. Y.; Li, J.; Wang, L. H.; Ge, Z. L.; Li, Q. Programming cell communications with pH-responsive DNA nanodevices. Chem. Commun. 2021, 57, 4536–4539.
Li, F.; Yu, W. T.; Zhang, J. J.; Dong, Y. H.; Ding, X. H.; Ruan, X. H.; Gu, Z.; Yang, D. Y. Spatiotemporally programmable cascade hybridization of hairpin DNA in polymeric nanoframework for precise siRNA delivery. Nat. Commun. 2021, 12, 1138.
Li, F.; Lv, Z. Y.; Zhang, X.; Dong, Y. H.; Ding, X. H.; Li, Z. M.; Li, S.; Yao, C.; Yang, D. Y. Supramolecular self-assembled DNA nanosystem for synergistic chemical and gene regulations on cancer cells. Angew. Chem., Int. Ed. 2021, 60, 25557–25566.
Yang, S.; Wu, J. L.; Wang, Z. Y.; Cheng, Y.; Zhang, R.; Yao, C.; Yang, D. Y. A smart DNA hydrogel enables synergistic immunotherapy and photodynamic therapy of melanoma. Angew. Chem., Int. Ed. 2024, 63, e202319073.
Song, N. C.; Chu, Y. W.; Li, S.; Fan, X. T.; Tang, J. P.; Li, H. J.; Tao, R. Y.; Li, F. Q.; Li, J. R.; Yang, D. Y. et al. A dual-enzyme-responsive DNA-based nanoframework enables controlled co-delivery of CRISPR-Cas9 and antisense oligodeoxynucleotide for synergistic gene therapy. Adv. Funct. Mater. 2023, 33, 2306634.
Chen, Z. G.; Yang, S.; Zhao, Z. Y.; Feng, L.; Sheng, J.; Deng, R. J.; Wang, B. P.; He, Y.; Luo, D.; Chen, M. et al. Smart tumor cell-derived DNA nano-tree assembly for on-demand macrophages reprogramming. Adv. Sci. 2024, 11, 2307188.
Hu, Y. W.; Gao, S. J.; Lu, H. F.; Tan, S. S.; Chen, F.; Ke, Y. J.; Ying, J. Y. A self-immolative DNA nanogel vaccine toward cancer immunotherapy. Nano Lett. 2023, 23, 9778–9787.
Li, S. P.; Jiang, Q.; Liu, S. L.; Zhang, Y. L.; Tian, Y. H.; Song, C.; Wang, J.; Zou, Y. G.; Anderson, G. J.; Han, J. Y. et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat. Biotechnol. 2018, 36, 258–264.
Zhang, P. H.; Gao, D.; An, K. L.; Shen, Q.; Wang, C.; Zhang, Y. C.; Pan, X. S.; Chen, X. G.; Lyv, Y. F.; Cui, C. et al. A programmable polymer library that enables the construction of stimuli-responsive nanocarriers containing logic gates. Nat. Chem. 2020, 12, 381–390.
Harris, A. L. Hypoxia-a key regulatory factor in tumour growth. Nat. Rev. Cancer 2002, 2, 38–47.
Webb, B. A.; Chimenti, M.; Jacobson, M. P.; Barber, D. L. Dysregulated pH: A perfect storm for cancer progression. Nat. Rev. Cancer 2011, 11, 671–677.
Fischer, A.; Ehrlich, A.; Plotkin, Y.; Ouyang, Y.; Asulin, K.; Konstantinos, I.; Fan, C. H.; Nahmias, Y.; Willner, I. Stimuli-responsive hydrogel microcapsules harnessing the COVID-19 immune response for cancer therapeutics. Angew. Chem., Int. Ed. 2023, 62, e202311590.
Sun, L. L.; Shen, F. Y.; Tian, L. L.; Tao, H. Q.; Xiong, Z. J.; Xu, J.; Liu, Z. ATP-responsive smart hydrogel releasing immune adjuvant synchronized with repeated chemotherapy or radiotherapy to boost antitumor immunity. Adv. Mater. 2021, 33, 2007910.
Wang, D. Y.; Liu, J. W.; Duan, J.; Yi, H.; Liu, J. J.; Song, H. W.; Zhang, Z. Z.; Shi, J. J.; Zhang, K. X. Enrichment and sensing tumor cells by embedded immunomodulatory DNA hydrogel to inhibit postoperative tumor recurrence. Nat. Commun. 2023, 14, 4511.
Velusamy, A.; Sharma, R.; Rashid, S. A.; Ogasawara, H.; Salaita, K. DNA mechanocapsules for programmable piconewton responsive drug delivery. Nat. Commun. 2024, 15, 704.
Rajasooriya, T.; Ogasawara, H.; Dong, Y. X.; Mancuso, J. N.; Salaita, K. Force-triggered self-destructive hydrogels. Adv. Mater. 2023, 35, 2305544.
Ma, Y. H.; Zhu, Y.; Wu, H.; He, Y.; Zhang, Q.; Huang, Q. L.; Wang, Z. M.; Xing, H.; Qiu, L. P.; Tan, W. H. Domain-targeted membrane partitioning of specific proteins with DNA nanodevices. J. Am. Chem. Soc. 2024, 146, 7640–7648.
Comberlato, A.; Koga, M. M.; Nüssing, S.; Parish, I. A.; Bastings, M. M. C. Spatially controlled activation of toll-like receptor 9 with DNA-based nanomaterials. Nano Lett. 2022, 22, 2506–2513.
Sun, L. L.; Shen, F. Y.; Xu, J.; Han, X.; Fan, C. H.; Liu, Z. DNA-edited ligand positioning on red blood cells to enable optimized T cell activation for adoptive immunotherapy. Angew. Chem., Int. Ed. 2020, 59, 14842–14853.
Shi, P.; Wang, X. L.; Davis, B.; Coyne, J.; Dong, C.; Reynolds, J.; Wang, Y. In situ synthesis of an aptamer-based polyvalent antibody mimic on the cell surface for enhanced interactions between immune and cancer cells. Angew. Chem. , Int. Ed. 2020, 59, 11892–11897.
Tang, R.; Fu, Y. H.; Gong, B.; Fan, Y. Y.; Wang, H. H.; Huang, Y.; Nie, Z.; Wei, P. A chimeric conjugate of antibody and programmable DNA nanoassembly smartly activates T cells for precise cancer cell targeting. Angew. Chem., Int. Ed. 2022, 61, e202205902.
Du, Y. L.; Lyu, Y. F.; Lin, J.; Ma, C. R.; Zhang, Q.; Zhang, Y. T.; Qiu, L. P.; Tan, W. H. Membrane-anchored DNA nanojunctions enable closer antigen-presenting cell-T-cell contact in elevated T-cell receptor triggering. Nat. Nanotechnol. 2023, 18, 818–827.
Li, F.; Sun, X. L.; Yang, J.; Ren, J.; Huang, M. X.; Wang, S. Q.; Yang, D. Y. A thermal and enzymatic dual-stimuli responsive DNA-based nanomachine for controlled mRNA delivery. Adv. Sci. 2023, 10, 2204905.
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