A DNA nanostructure-Hif-1α inducer complex as novel nanotherapy against cisplatin-induced acute kidney injury

Abstract

Since its discovery in 1978, cisplatin-based chemotherapy regimens have served a pivotal role in human cancer treatment, saving millions of lives. However, its high risk still poses a significant challenge for cisplatin-induced acute kidney injury (AKI), which occurs in 30% of cisplatin-treated patients. Unfortunately, no effective solution for preventing or managing this severe complication, which greatly impacts its clinical administration. Kidney is the main organ injured by cisplatin, and the injury is related to cisplatin-induced cell apoptosis and DNA injury. Therefore, to achieve the safe use of cisplatin in tumour treatment, the key lies in identifying a kidney treatment that can effectively minimize cisplatin nephrotoxicity. Here, we successfully synthesized and applied a DNA-nanostructure complex, named TFG, which contains tetrahedral framework nucleic acids (tFNAs) and FG-4592, a novel Hif-1α inducer. As cargo, TFG is composed entirely of DNA strands. It possesses low nephrotoxicity and renal aggregation properties while FG-4592 is able to relieve renal injury by downregulating the apoptosis signal pathways. And it can relieve cisplatin-induced renal injury when taken cisplatin treatment. This work aims to enhance chemotherapy protection in tumour patients by using TFG, a DNA-based nanomedicines to kidney. This work has the potential to revolutionize the treatment of renal diseases, particularly drug-induced kidney injury, leading to improved clinical outcomes.

References

[1] Chattopadhyay D. Cisplatin. Resonance. 2022;27:659-666.

[2] Bosl GJBD, Sheinfeld J. Cancer of the Testis. Lippincott Williams & Wilkins; 2001.

[3] Tang C, Livingston MJ, Safirstein R, Dong Z. Cisplatin nephrotoxicity: new insights and therapeutic implications. Nat Rev Nephrol. 2023;19:53-72.

[4] Yimit A, Adebali O, Sancar A, Jiang Y. Differential damage and repair of DNA-adducts induced by anti-cancer drug cisplatin across mouse organs. Nat Commun. 2019;10:309.

[5] Wang D, Lippard SJ. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov. 2005;4:307-320.

[6] Liu Z, Tan S, Zu Y, Fu Y, Meng R, Xing Z. The interactions of cisplatin and DNA studied by atomic force microscopy. Micron. 2010;41:833-839.

[7] Freyer DR, Frazier AL, Sung L. Sodium thiosulfate and cisplatin-induced hearing loss. N Engl J Med. 2018;379:1180-1181.

[8] Brock PR, Maibach R, Childs M, et al. Sodium thiosulfate for protection from cisplatin-induced hearing loss. N Engl J Med. 2018;378:2376-2385.

[9] Chen F, Chen J, Yang L, et al. Extracellular vesicle-packaged HIF-1alpha-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol. 2019;21:498-510.

[10] Li G, Ko CN, Li D, et al. A small molecule HIF-1alpha stabilizer that accelerates diabetic wound healing. Nat Commun. 2021;12:3363.

[11] Chen N, Hao C, Liu BC, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. N Engl J Med. 2019;381:1011-1022.

[12] Yang Y, Yu X, Zhang Y, et al. Hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) protects against cisplatin-induced acute kidney injury. Clin Sci (Lond). 2018;132:825-838.

[13] Fu Z, Wang Z, Xu L, et al. HIF-1α-BNIP3-mediated mitophagy in tubular cells protects against renal ischemia/reperfusion injury. Redox Biol. 2020;36:101671.

[14] Pharmacopedia C. Guideline on Bioanalytical Method Validation. European Medicines Agency; 2015.

[15] You X, Guo B, Wang Z, Ma H, Zhang X. Label-free quantitative proteomic analysis of serum exosomes from patients of renal anemia: the good and the bad of Roxadustat. Clin Proteomics. 2022;19:21.

[16] Seeman NC. Nucleic acid junctions and lattices. J Theor Biol. 1982;99:237-247.

[17] Watson JD, Crick FH. Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature. 1953;171:737-738.

[18] Madhanagopal BR, Zhang S, Demirel E, Wady H, Chandrasekaran AR. DNA nanocarriers: programmed to deliver. Trends Biochem Sci. 2018;43:997-1013.

[19] Zhang T, Ma H, Zhang X, Shi S, Lin Y. Functionalized DNA nanomaterials targeting toll-like receptor 4 prevent bisphosphonate-related osteonecrosis of the jaw via regulating mitochondrial homeostasis in macrophages. Adv Funct Mater. 2023;33:2213401.

[20] Zhang T, Zhou M, Xiao D, et al. Myelosuppression alleviation and hematopoietic regeneration by tetrahedral-framework nucleic-acid nanostructures functionalized with osteogenic growth peptide. Adv Sci. 2022;9:2202058.

[21] Zhang M, Wen Y, Huang Z, et al. Targeted therapy for autoimmune diseases based on multifunctional frame nucleic acid system: blocking TNF-α-NF-κB signaling and mediating macrophage polarization. Chem Eng J. 2023;454:140399.

[22] Liu Z, Chen X, Ma W, et al. Suppression of lipopolysaccharide-induced sepsis by tetrahedral framework nucleic acid loaded with quercetin. Adv Funct Mater. 2022;32:2204587.

[23] Zhang Q, Lin S, Wang L, et al. Tetrahedral framework nucleic acids act as antioxidants in acute kidney injury treatment. Chem Eng J. 2021;413:127426.

[24] Chen R, Wen D, Fu W, et al. Treatment effect of DNA framework nucleic acids on diffuse microvascular endothelial cell injury after subarachnoid hemorrhage. Cell Prolif. 2022;55:e13206.

[25] Shao X, Hu Z, Zhan Y, Ma W, Quan L, Lin Y. MiR-26a-tetrahedral framework nucleic acids mediated osteogenesis of adipose-derived mesenchymal stem cells. Cell Prolif. 2022;55:e13272.

[26] Lin S, Zhang Q, Li S, Qin X, Cai X, Wang H. Tetrahedral framework nucleic acids-based delivery promotes intracellular transfer of healing peptides and accelerates diabetic would healing. Cell Prolif. 2022;55:e13279.

[27] Yan R, Cui W, Ma W, Li J, Liu Z, Lin Y. Typhaneoside-tetrahedral framework nucleic acids system: mitochondrial recovery and antioxidation for acute kidney injury treatment. ACS Nano. 2023;17:8767-8781.

[28] Schwartz SA, Perry S. Patient protection in cancer chemotherapy. JAMA. 1966;197:623-627.

[29] Ma W, Yang Y, Zhu J, et al. Biomimetic nanoerythrosome-coated aptamer–DNA tetrahedron/Maytansine conjugates: pH-responsive and targeted cytotoxicity for HER2-positive breast cancer. Adv Mater. 2022;34:2109609.

[30] Andersen ES, Dong M, Nielsen MM, et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature. 2009;459:73-76.

[31] Li X, Zou Y, Xing J, et al. Pretreatment with Roxadustat (FG-4592) attenuates folic acid-induced kidney injury through Antiferroptosis via Akt/GSK-3β/Nrf2 pathway. Oxid Med Cell Longev. 2020;2020:1-17.

[32] Sirong S, Yang C, Taoran T, et al. Effects of tetrahedral framework nucleic acid/wogonin complexes on osteoarthritis. Bone Res. 2020;8:6.

[33] Lerman LS. Structural considerations in the interaction of DNA and acridines. J Mol Biol. 1961;3:18-30.

[34] Yoo YJ, Lee CH, Park SH, Lim YT. Nanoparticle-based delivery strategies of multifaceted immunomodulatory RNA for cancer immunotherapy. J Control Release. 2022;343:564-583.

[35] Wolf MT, Wu XR, Huang CL. Uromodulin upregulates TRPV5 by impairing caveolin-mediated endocytosis. Kidney Int. 2013;84:130-137.

[36] Hamroun A, Lenain R, Bigna JJ, et al. Prevention of cisplatin-induced acute kidney injury: a systematic review and meta-analysis. Drugs. 2019;79:1567-1582.

[37] Tian T, Zhang T, Shi S, Gao Y, Cai X, Lin Y. A dynamic DNA tetrahedron framework for active targeting. Nat Protoc. 2023;18:1028-1055.

[38] Mossoba ME, Sprando RL. In vitro to in vivo concordance of toxicity using the human proximal tubule cell line HK-2. Int J Toxicol. 2020;39:452-464.

[39] Czock D, Keller F. Clinical pharmacokinetics and pharmacodynamics of Roxadustat. Clin Pharmacokinet. 2022;61:347-362.

[40] Ghadi R, Dand N. BCS class IV drugs: highly notorious candidates for formulation development. J Control Release. 2017;248:71-95.

[41] Liu N, Zhang X, Li N, et al. Tetrahedral framework nucleic acids promote corneal epithelial wound healing in vitro and in vivo. Small. 2019;15:e1901907.

[42] Kim H, Lee H, Lee G, et al. Phospholipase A2 inhibits cisplatin-induced acute kidney injury by modulating regulatory T cells by the CD206 mannose receptor. Kidney Int. 2015;88:550-559.

[43] Tang TT, Wang B, Wu M, et al. Extracellular vesicle-encapsulated IL-10 as novel nanotherapeutics against ischemic AKI. Sci Adv. 2020;6:eaaz748.

[44] Ko VH, Yu LJ, Dao DT, et al. Roxadustat (FG-4592) accelerates pulmonary growth, development, and function in a compensatory lung growth model. Angiogenesis. 2020;23:637-649.

[45] Tang TT, Wang B, Li ZL, et al. Kim-1 targeted extracellular vesicles: a new therapeutic platform for RNAi to treat AKI. J Am Soc Nephrol. 2021;32:2467-2483.

[46] Yangyang Wang WJJZ. Tetrahedral framework nucleic acids promote cognitive impairment recovery post traumatic brain injury. Chin Chem Lett. 2023;34:107746.

[47] Yang X, Zhang F, Du Y, et al. Effect of tetrahedral DNA nanostructures on LPS-induced neuroinflammation in mice. Chin Chem Lett. 2022;33:1901-1906.

[48] Liu Y, Li S, Lin S, et al. A tetrahedral framework nucleic acid based multifunctional nanocapsule for tumor prophylactic mRNA vaccination. Chin Chem Lett. 2023;34:107987.

[49] Hulley PA, Papadimitriou-Olivgeri I, Knowles HJ. Osteoblast-osteoclast coculture amplifies inhibitory effects of FG-4592 on human osteoclastogenesis and reduces bone resorption. JBMR Plus. 2020;4:e10370.

[50] Tang D, Zhang J, Yan T, et al. FG-4592 accelerates cutaneous wound healing by epidermal stem cell activation via HIF-1alpha stabilization. Cell Physiol Biochem. 2018;46:2460-2470.

RIGHTS & PERMISSIONS

2024 2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.