Advertisement

Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy

  • Jie Chen (陈杰)
  • Lin Lin (林琳)
  • Nan Yan (燕楠)
  • Yingying Hu (胡莹莹)
  • Huapan Fang (方华攀)
  • Zhaopei Guo (郭兆培)
  • Pingjie Sun (孙平杰)
  • Huayu Tian (田华雨)
  • Xuesi Chen (陈学思)
Articles Special Issue: Diagnostic and Theranostic Platforms Based on Dendrimers and Hyperbranched Polymers
  • 150 Downloads

Abstract

Nano-therapeutic approach for clinical implementation of tumors remains a longstanding challenge in the medical field. The main challenges are rapid clearance, offtarget effect and the limited role in the treatment of metastatic tumors. Toward this objective, a cell-mediated strategy by transporting photothermal reagents and CpG adjuvant within macrophage vehicles is performed. The photothermal reagents are constructed by conjugating of hyperbranched polyethyleimine (PEI) to golden nanorode (GNR) via S-Au bonds. GNR-PEI/CpG nanocomposites, formed via electrostatic interaction and displayed excellent near-infrared (NIR) photothermal performance, exhibit immense macrophage uptake and negligible cytotoxic effect, which is essential for the fabrication of GNR-PEI/CpG loaded macrophages. GNR-PEI/ CpG loaded macrophages demonstrated admirable photothermal response in vitro. Benefited from the functionalization of the binding adhesion between macrophages and 4T1 cells, GNR-PEI/CpG loaded macrophages significantly promoted tumor accumulation in vivo and dramatically enhanced the efficiency of photothermal cancer therapy. Moreover, the immune system is activated after photothermal therapy, which is mainly attributed to the generation of tumor specific antigens and CpG adjuvant in situ. Our findings provide a potential cell-mediated nanoplatform for tumor therapy by combination of near infrared photothermal therapy and immunotherapy.

Keywords

hyperbranched polymers immunotherapy macrophages photothermal therapy synergistic treatment 

载GNR-PEI/CpG巨噬细胞用于肿瘤的光热和免疫联合治疗

摘要

纳米药物在肿瘤治疗的临床应用是生物医学领域中长期存在的挑战. 主要问题包括: 体内快速清除、脱靶现象以及对转移瘤治疗 的局限性. 本论文用超支化PEI对金纳米棒进行修饰, 获得了带有正电性的GNR-PEI, 再与负电性的CpG佐剂进行静电复合, 形成GNRPEI/ CpG纳米复合物. 为了提高体内适用性和靶向性, 我们进一步构建了载GNR-PEI/CpG的巨噬细胞, 用于肿瘤的光热和免疫联合治疗. 体外研究结果表明, 巨噬细胞具有高效的担载GNR-PEI/CpG的能力, 且载GNR-PEI/CpG巨噬细胞具有很好的光热转换能力. 体内研究结 果进一步预示了该策略在肿瘤治疗领域的巨大潜力.

Notes

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (51390484, 21474104, 51403205, 51503200 and 51520105004), National program for support of Top-notch young professionals, and Jilin province science and technology development program (20160204032GX, 20180414027GH).

Supplementary material

40843_2018_9238_MOESM1_ESM.pdf (349 kb)
Macrophages loaded CpG and GNR-PEI for combination of tumor photothermal therapy and immunotherapy

References

  1. 1.
    Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA-A Cancer J Clinicians, 2015, 66: 115–132CrossRefGoogle Scholar
  2. 2.
    Xu C, Tian H, Chen X. Recent progress in cationic polymeric gene carriers for cancer therapy. Sci China Chem, 2017, 60: 319–328CrossRefGoogle Scholar
  3. 3.
    Chen J, Dong X, Feng T, et al. Charge-conversional zwitterionic copolymer as pH-sensitive shielding system for effective tumor treatment. Acta Biomater, 2015, 26: 45–53CrossRefGoogle Scholar
  4. 4.
    Wang G, Song W, Shen N, et al. Curcumin-encapsulated polymeric nanoparticles for metastatic osteosarcoma cells treatment. Sci China Mater, 2017, 60: 995–1007CrossRefGoogle Scholar
  5. 5.
    Lin L, Guo Z, Chen J, et al. Synthesis and characterization of polyphenylalanine grafted low molecular weight PEI as efficient gene carriers. Acta Polym Sin, 2017, 2: 321-328Google Scholar
  6. 6.
    Xia J, Tian H, Chen J, et al. Polyglutamic acid based polyanionic shielding system for polycationic gene carriers. Chin J Polym Sci, 2016, 34: 316–323CrossRefGoogle Scholar
  7. 7.
    Sun W, Gu Z. Tailoring non-viral delivery vehicles for transporting genome-editing tools. Sci China Mater, 2017, 60: 511–515CrossRefGoogle Scholar
  8. 8.
    Chen J, Liang H, Lin L, et al. Gold-nanorods-based gene carriers with the capability of photoacoustic imaging and photothermal therapy. ACS Appl Mater Interfaces, 2016, 8: 31558–31566CrossRefGoogle Scholar
  9. 9.
    Zhu H, Chen Y, Yan FJ, et al. Polysarcosine brush stabilized gold nanorods for in vivo near-infrared photothermal tumor therapy. Acta Biomater, 2017, 50: 534–545CrossRefGoogle Scholar
  10. 10.
    Ye Y, Wang C, Zhang X, et al. A melanin-mediated cancer immunotherapy patch. Sci Immunol, 2017, 2: eaan5692–5692CrossRefGoogle Scholar
  11. 11.
    Niu Y, Song W, Zhang D, et al. Functional computer-to-plate nearinfrared absorbers as highly efficient photoacoustic dyes. Acta Biomater, 2016, 43: 262–268CrossRefGoogle Scholar
  12. 12.
    Virani NA, Davis C, McKernan P, et al. Phosphatidylserine targeted single-walled carbon nanotubes for photothermal ablation of bladder cancer. Nanotechnology, 2018, 29: 035101CrossRefGoogle Scholar
  13. 13.
    Mathiyazhakan M, Upputuri PK, Sivasubramanian K, et al. In situ synthesis of gold nanostars within liposomes for controlled drug release and photoacoustic imaging. Sci China Mater, 2016, 59: 892–900CrossRefGoogle Scholar
  14. 14.
    Yang J, Yao MH, Du MS, et al. A near-infrared light-controlled system for reversible presentation of bioactive ligands using polypeptide-engineered functionalized gold nanorods. Chem Commun, 2015, 51: 2569–2572CrossRefGoogle Scholar
  15. 15.
    Liu Y, Yang M, Zhang J, et al. Human induced pluripotent stem cells for tumor targeted delivery of gold nanorods and enhanced photothermal therapy. ACS Nano, 2016, 10: 2375–2385CrossRefGoogle Scholar
  16. 16.
    Choi WI, Kim JY, Kang C, et al. Tumor regression in vivo by photothermal therapy based on gold-nanorod-loaded, functional nanocarriers. ACS Nano, 2011, 5: 1995–2003CrossRefGoogle Scholar
  17. 17.
    Luo GF, Chen WH, Lei Q, et al. A triple-collaborative strategy for high-performance tumor therapy by multifunctional mesoporous silica-coated gold nanorods. Adv Funct Mater, 2016, 26: 4339–4350CrossRefGoogle Scholar
  18. 18.
    Wang BK, Yu XF, Wang JH, et al. Gold-nanorods-siRNA nanoplex for improved photothermal therapy by gene silencing. Biomaterials, 2016, 78: 27–39CrossRefGoogle Scholar
  19. 19.
    Wang F, Shen Y, Zhang W, et al. Efficient, dual-stimuli responsive cytosolic gene delivery using a RGD modified disulfide-linked polyethylenimine functionalized gold nanorod. J Control Release, 2014, 196: 37–51CrossRefGoogle Scholar
  20. 20.
    Chen J, Jiao Z, Lin L, et al. Polylysine-modified polyethylenimines as siRNA carriers for effective tumor treatment. Chin J Polym Sci, 2015, 33: 830–837CrossRefGoogle Scholar
  21. 21.
    Chen Z, Zhao P, Luo Z, et al. Cancer cell membrane–biomimetic nanoparticles for homologous-targeting dual-modal imaging and photothermal therapy. ACS Nano, 2016, 10: 10049–10057CrossRefGoogle Scholar
  22. 22.
    Chen J, Guo Z, Tian H, et al. Production and clinical development of nanoparticles for gene delivery. Mol Ther -Methods Clinical Dev, 2016, 3: 16023CrossRefGoogle Scholar
  23. 23.
    Guan X, Guo Z, Lin L, et al. Ultrasensitive pH triggered charge/size dual-rebound gene delivery system. Nano Lett, 2016, 16: 6823–6831CrossRefGoogle Scholar
  24. 24.
    Guo Z, Chen J, Lin L, et al. pH triggered size increasing gene carrier for efficient tumor accumulation and excellent antitumor effect. ACS Appl Mater Interfaces, 2017, 9: 15297–15306CrossRefGoogle Scholar
  25. 25.
    Cheng Y, Dai Q, Morshed RA, et al. Blood-brain barrier permeable gold nanoparticles: an efficient delivery platform for enhanced malignant glioma therapy and imaging. Small, 2014, 359Google Scholar
  26. 26.
    Li Z, Shao J, Luo Q, et al. Cell-borne 2D nanomaterials for efficient cancer targeting and photothermal therapy. Biomaterials, 2017, 133: 37–48CrossRefGoogle Scholar
  27. 27.
    Patel SK, Janjic JM. Macrophage targeted theranostics as personalized nanomedicine strategies for inflammatory diseases. Theranostics, 2015, 5: 150–172CrossRefGoogle Scholar
  28. 28.
    Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell, 2010, 141: 39–51CrossRefGoogle Scholar
  29. 29.
    Cao H, Dan Z, He X, et al. Liposomes coated with isolated macrophage membrane can target lung metastasis of breast cancer. ACS Nano, 2016, 10: 7738–7748CrossRefGoogle Scholar
  30. 30.
    Choi MR, Stanton-Maxey KJ, Stanley JK, et al. A cellular trojan horse for delivery of therapeutic nanoparticles into tumors. Nano Lett, 2007, 7: 3759–3765CrossRefGoogle Scholar
  31. 31.
    Li Z, Huang H, Tang S, et al. Small gold nanorods laden macrophages for enhanced tumor coverage in photothermal therapy. Biomaterials, 2016, 74: 144–154CrossRefGoogle Scholar
  32. 32.
    Xie YQ, Wei L, Tang L. Immunoengineering with biomaterials for enhanced cancer immunotherapy. WIREs Nanomed Nanobiotechnol, 2018, 28: e1506CrossRefGoogle Scholar
  33. 33.
    Liu L, Guo Z, Xu L, et al. Facile purification of colloidal NIRresponsive gold nanorods using ions assisted self-assembly. Nanoscale Res Lett, 2011, 6: 143CrossRefGoogle Scholar
  34. 34.
    Lohse SE, Murphy CJ. The quest for shape control: a history of gold nanorod synthesis. Chem Mater, 2013, 25: 1250–1261CrossRefGoogle Scholar
  35. 35.
    Deng X, Li K, Cai X, et al. A hollow-structured CuS@Cu2S@Au nanohybrid: synergistically enhanced photothermal efficiency and photoswitchable targeting effect for cancer theranostics. Adv Mater, 2017, 29: 1701266CrossRefGoogle Scholar
  36. 36.
    Shen J, Kim HC, Mu C, et al. Multifunctional gold nanorods for siRNA gene silencing and photothermal therapy. Adv Healthcare Mater, 2014, 3: 1629–1637CrossRefGoogle Scholar
  37. 37.
    Guo L, Yan DD, Yang D, et al. Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles. ACS Nano, 2014, 8: 5670–5681CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Jie Chen (陈杰)
    • 1
  • Lin Lin (林琳)
    • 1
  • Nan Yan (燕楠)
    • 1
  • Yingying Hu (胡莹莹)
    • 1
  • Huapan Fang (方华攀)
    • 1
  • Zhaopei Guo (郭兆培)
    • 1
  • Pingjie Sun (孙平杰)
    • 2
  • Huayu Tian (田华雨)
    • 1
  • Xuesi Chen (陈学思)
    • 1
  1. 1.Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunChina
  2. 2.Changchun Golden Transfer Science and Technology Co. Ltd.ChangchunChina

Personalised recommendations