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Traceless photodegradable polymer cocoons for universal protein delivery and light-controlled gene editing

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Abstract

Polymer conjugation was found highly valuable in clinic to improve the bioavailability of protein therapeutics. However, it is still a tremendous challenge to achieve a complete release of original proteins from the conjugated hybrid under external stimulus to recover active proteins in the targeted tissue. Herein, we report a general light-controlled protein delivery methodology by weaving a photodegradable polymer cocoon around proteins, which could reliably protect them from degradation in the dark while efficiently releasing them under illumination without any residual atoms. The surface charge of the polymer shell is easily tunable to facilitate efficient cell uptake. The versatility of this strategy is demonstrated by the delivery of the Cas9/sgRNA complex that realized light-controlled gene editing both in vitro and in vivo, and such repertoire is of particular value in regard to minimizing the off-target toxicity of CRISPR-Cas9-based gene therapy.

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References

  1. Leader B, Baca QJ, Golan DE. Nat Rev Drug Discov, 2008, 7: 21–39

    Article  PubMed  CAS  Google Scholar 

  2. Scaletti F, Hardie J, Lee YW, Luther DC, Ray M, Rotello VM. Chem Soc Rev, 2018, 47: 3421–3432

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Chen WH, Chen QW, Chen Q, Cui C, Duan S, Kang Y, Liu Y, Liu Y, Muhammad W, Shao S, Tang C, Wang J, Wang L, Xiong MH, Yin L, Zhang K, Zhang Z, Zhen X, Feng J, Gao C, Gu Z, He C, Ji J, Jiang X, Liu W, Liu Z, Peng H, Shen Y, Shi L, Sun X, Wang H, Wang J, Xiao H, Xu FJ, Zhong Z, Zhang XZ, Chen X. Sci China Chem, 2022, 65: 1010–1075

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Wu Y, Zheng J, Zeng Q, Zhang T, Xing D. Nano Res, 2020, 13: 2399–2406

    Article  CAS  Google Scholar 

  5. Yu Y, Wu X, Guan N, Shao J, Li H, Chen Y, Ping Y, Li D, Ye H. Sci Adv, 2020, 6: eabb1777

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  6. Chen Y, Yan X, Ping Y. ACS Mater Lett, 2020, 2: 644–653

    Article  CAS  Google Scholar 

  7. Aksoy YA, Yang B, Chen W, Hung T, Kuchel RP, Zammit NW, Grey ST, Goldys EM, Deng W. ACS Appl Mater Interfaces, 2020, 12: 52433–52444

    Article  PubMed  CAS  Google Scholar 

  8. Li H, Fan X, Chen X. ACS Appl Mater Interfaces, 2016, 8: 4500–4507

    Article  PubMed  CAS  Google Scholar 

  9. Pan Y, Yang J, Luan X, Liu X, Li X, Yang J, Huang T, Sun L, Wang Y, Lin Y, Song Y. Sci Adv, 2019, 5: eaav7199

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  10. Zhao H, Li Y, He L, Pu W, Yu W, Li Y, Wu YT, Xu C, Wei Y, Ding Q, Song BL, Huang H, Zhou B. Circulation, 2020, 141: 67–79

    Article  PubMed  CAS  Google Scholar 

  11. Rosenblum D, Gutkin A, Kedmi R, Ramishetti S, Veiga N, Jacobi AM, Schubert MS, Friedmann-Morvinski D, Cohen ZR, Behlke MA, Lieberman J, Peer D. Sci Adv, 2020, 6: eabc9450

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  12. Lino CA, Harper JC, Carney JP, Timlin JA. Drug Deliver, 2018, 25: 1234–1257

    Article  CAS  Google Scholar 

  13. Khalaf K, Janowicz K, Dyszkiewicz-Konwińska M, Hutchings G, Dompe C, Moncrieff L, Jankowski M, Machnik M, Oleksiewicz U, Kocherova I, Petitte J, Mozdziak P, Shibli JA, Iżycki D, Józkowiak M, Piotrowska-Kempisty H, Skowroński MT, Antosik P, Kempisty B. Genes, 2020, 11: 921

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Simhadri VL, Hopkins L, McGill JR, Duke BR, Mukherjee S, Zhang K, Sauna ZE. Nat Commun, 2021, 12: 5090

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  15. Sun B, Chen H, Gao X. J Control Release, 2021, 337: 698–717

    Article  PubMed  CAS  Google Scholar 

  16. Zhang S, Shen J, Li D, Cheng Y. Theranostics, 2021, 11: 614–648

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Wang HX, Li M, Lee CM, Chakraborty S, Kim HW, Bao G, Leong KW. Chem Rev, 2017, 117: 9874–9906

    Article  PubMed  CAS  Google Scholar 

  18. Nihongaki Y, Kawano F, Nakajima T, Sato M. Nat Biotechnol, 2015, 33: 755–760

    Article  PubMed  CAS  Google Scholar 

  19. Hemphill J, Borchardt EK, Brown K, Asokan A, Deiters A. J Am Chem Soc, 2015, 137: 5642–5645

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Wang Y, Liao S, Guan N, Liu Y, Dong K, Weber W, Ye H. Sci Adv, 2020, 6: eabb9484

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  21. Zhang Y, Ling X, Su X, Zhang S, Wang J, Zhang P, Feng W, Zhu YY, Liu T, Tang X. Angew Chem Int Ed, 2020, 59: 20895–20899

    Article  CAS  Google Scholar 

  22. Zhou W, Brown W, Bardhan A, Delaney M, Ilk AS, Rauen RR, Kahn SI, Tsang M, Deiters A. Angew Chem Int Ed, 2020, 59: 8998–9003

    Article  CAS  Google Scholar 

  23. Zhang D, Liu L, Jin S, Tota E, Li Z, Piao X, Zhang X, Fu XD, Devaraj NK. J Am Chem Soc, 2022, 144: 4487–4495

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Ng DYW, Arzt M, Wu Y, Kuan SL, Lamla M, Weil T. Angew Chem Int Ed, 2014, 53: 324–328

    Article  CAS  Google Scholar 

  25. Lu R, Zheng Y, Wang M, Lin J, Zhao Z, Chen L, Zhang J, Liu X, Yin L, Chen Y. Acta Biomater, 2022, 152: 355–366

    Article  PubMed  CAS  Google Scholar 

  26. Sangsuwan R, Tachachartvanich P, Francis MB. J Am Chem Soc, 2019, 141: 2376–2383

    Article  PubMed  CAS  Google Scholar 

  27. Yan M, Du J, Gu Z, Liang M, Hu Y, Zhang W, Priceman S, Wu L, Zhou ZH, Liu Z, Segura T, Tang Y, Lu Y. Nat Nanotech, 2010, 5: 48–53

    Article  ADS  CAS  Google Scholar 

  28. Liu X, Gao W. ACS Appl Mater Interfaces, 2017, 9: 2023–2028

    Article  PubMed  CAS  Google Scholar 

  29. Ye Y, Yu J, Gu Z. Macromol Chem Phys, 2016, 217: 333–343

    Article  CAS  Google Scholar 

  30. Yan J, Liu X, Wu F, Ge C, Ye H, Chen X, Wei Y, Zhou R, Duan S, Zhu R, Zheng Y, Yin L. Adv Mater, 2022, 34: 2109517

    Article  CAS  Google Scholar 

  31. Chen G, Abdeen AA, Wang Y, Shahi PK, Robertson S, Xie R, Suzuki M, Pattnaik BR, Saha K, Gong S. Nat Nanotechnol, 2019, 14: 974–980

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  32. Zou Y, Sun X, Yang Q, Zheng M, Shimoni O, Ruan W, Wang Y, Zhang D, Yin J, Huang X, Tao W, Park JB, Liang XJ, Leong KW, Shi B. Sci Adv, 2022, 8: eabm8011

    Article  ADS  Google Scholar 

  33. Sun J, Liu X, Guo J, Zhao W, Gao W. ACS Appl Mater Interfaces, 2021, 13: 88–96

    Article  PubMed  CAS  Google Scholar 

  34. Sun J, Guo J, Zhang L, Gong L, Sun Y, Deng X, Gao W. J Control Release, 2023, 356: 175–184

    Article  PubMed  CAS  Google Scholar 

  35. Zhang Q, Li M, Zhu C, Nurumbetov G, Li Z, Wilson P, Kempe K, Haddleton DM. J Am Chem Soc, 2015, 137: 9344–9353

    Article  PubMed  CAS  Google Scholar 

  36. Pirrung MC, Wang L, Montague-Smith MP. Org Lett, 2001, 3: 1105–1108

    Article  PubMed  CAS  Google Scholar 

  37. McConnell KI, Shamsudeen S, Meraz IM, Mahadevan TS, Ziemys A, Rees P, Summers HD, Serda RE. J Biomed Nanotechnol, 2016, 12: 154–164

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Li L, Tang F, Liu H, Liu T, Hao N, Chen D, Teng X, He J. ACS Nano, 2010, 4: 6874–6882

    Article  PubMed  CAS  Google Scholar 

  39. Nan A, Bai X, Son SJ, Lee SB, Ghandehari H. Nano Lett, 2008, 8: 2150–2154

    Article  PubMed  ADS  CAS  Google Scholar 

  40. Behzadi S, Serpooshan V, Tao W, Hamaly MA, Alkawareek MY, Dreaden EC, Brown D, Alkilany AM, Farokhzad OC, Mahmoudi M. Chem Soc Rev, 2017, 46: 4218–4244

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Liu C, Wan T, Wang H, Zhang S, Ping Y, Cheng Y. Sci Adv, 2019, 5: eaaw8922

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  42. Helfer-Hungerbuehler AK, Shah J, Meili T, Boenzli E, Li P, Hofmann-Lehmann R. Viruses, 2021, 13: 1636

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Holmgaard A, Askou AL, Benckendorff JNE, Thomsen EA, Cai Y, Bek T, Mikkelsen JG, Corydon TJ. Mol Ther Nucl Acids, 2017, 9: 89–99

    Article  CAS  Google Scholar 

  44. Xie S. Int J Biol Sci, 2017, 13: 1470–1478

    Article  PubMed  PubMed Central  Google Scholar 

  45. Lederer CW. Int J Mol Sci, 2022, 23: 1082

    Article  PubMed  PubMed Central  Google Scholar 

  46. Rui Y, Wilson DR, Choi J, Varanasi M, Sanders K, Karlsson J, Lim M, Green JJ. Sci Adv, 2019, 5: eaay3255

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  47. Shahbazi R, Sghia-Hughes G, Reid JL, Kubek S, Haworth KG, Humbert O, Kiem HP, Adair JE. Nat Mater, 2019, 18: 1124–1132

    Article  PubMed  PubMed Central  ADS  CAS  Google Scholar 

  48. Xiao Q, Guo D, Chen S. Front Cell Infect Microbiol, 2019, 9: 1–15

    Article  Google Scholar 

  49. Hou Z, Chen S. Virol Sin, 2022, 37: 1–10

    Article  PubMed  PubMed Central  Google Scholar 

  50. Liu Z, Chen S, Jin X, Wang Q, Yang K, Li C, Xiao Q, Hou P, Liu S, Wu S, Hou W, Xiong Y, Kong C, Zhao X, Wu L, Li C, Sun G, Guo D. Cell Biosci, 2017, 7: 47

    Article  PubMed  PubMed Central  Google Scholar 

  51. Saikia C, Das MK, Ramteke A, Maji TK. Int J Biol Macromol, 2016, 93: 1121–1132

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the National Key R&D Program of China (2018YFA0903500), the Max-Planck Partner Group, the National Natural Science Foundation of China (22077042) and the National Key Research and Development Program of China (2022YFA1206001 to S. G.). We thank the Analytical and Testing Centre of HUST, Analytical and Testing Centre of School of Chemistry and Chemical Engineering (HUST), and the Research Core Facilities for Life Science (HUST) for instrument support.

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Authors and Affiliations

  1. Hubei Engineering Research Center for Biomaterials and Medical Protective Materials; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica; Key Laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education; School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China

    Huaibin Yu, Meron Tsegay Kifle & Yuzhou Wu

  2. Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, 450000, China

    Huaibin Yu

  3. College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan, 430074, China

    Lili Chen, Feihong Xiong, Yan Zhang & Shangbang Gao

  4. Institute of Medical Virology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China

    Wei Hou & Shuliang Chen

  5. College of Pharmacy, Shenzhen Technology University, Shenzhen, 518118, China

    Weining Zhao

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  1. Huaibin Yu
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  2. Meron Tsegay Kifle
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Correspondence to Yuzhou Wu.

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Supporting information The supporting information is available online at chem.scichina.com and link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Yu, H., Kifle, M.T., Chen, L. et al. Traceless photodegradable polymer cocoons for universal protein delivery and light-controlled gene editing. Sci. China Chem. 67, 664–676 (2024). https://doi.org/10.1007/s11426-023-1708-3

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  • DOI: https://doi.org/10.1007/s11426-023-1708-3

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