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Excipient-free porphyrin/SN-38 based nanotheranostics for drug delivery and cell imaging

  • Ye Yuan
  • Ruonan Bo
  • Di Jing
  • Zhao Ma
  • Zhongling Wang
  • Tzu-yin Lin
  • Lijie Dong
  • Xiangdong XueEmail author
  • Yuanpei LiEmail author
Research Article

Abstract

Nanotheranostics with comprehensive diagnostic and therapeutic capabilities show exciting cancer treatment potentials. Here, we develop an excipient-free drug delivery system for cancer diagnosis as well as therapy, in which a near infra-red photosensitizer and a chemotherapeutic drug can be self-delivered without any carriers. The building block of the drug delivery system was synthesized by covalently conjugating four anticancer drugs (7-ethyl-10-hydroxy-camptothecin, SN-38) with a photosensitizer (porphyrin) via hydrolyzable ester linkage, which endows the drug delivery system with 100% active pharmaceutical ingredients, excellent imaging, and therapeutic functionalities. The conjugates can readily self-assemble into nanosheets (PS NSs) and remain stable for at least 20 days in aqueous solution. In PS NSs, fluorescence resonance energy transfer (FRET) dominates the fluorescence of SN-38 and enables to monitor the drug release fluorescently. The PS NSs also show excellent anticancer activity in vitro, due to the increased cell uptake with the synergistic effect of photodynamic therapy and chemotherapy.

Keywords

porphyrin 7-ethyl-10-hydroxy-camptothecin (SN-38) drug delivery self-indication nanotheranostics photodynamic therapy 

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Notes

Acknowledgements

The authors gratefully acknowledge the support from Dr. Li’s faculty startup funds at UC Davis and Dr. Xue’s National Natural Science Foundation of China (NSFC) (No. 81803002).

Supplementary material

12274_2020_2641_MOESM1_ESM.pdf (2.6 mb)
Excipient-free porphyrin/SN-38 based nanotheranostics for drug delivery and cell imaging

References

  1. [1]
    Lin, S.; Xie, P. L.; Luo, M. M.; Li, Q.; Li, L.; Zhang, J. Z.; Zheng, Q. X.; Chen, H.; Nan, K. H. Efficiency against multidrug resistance by co-delivery of doxorubicin and curcumin with a legumain-sensitive nanocarrier. Nano Res.2018, 11, 3619–3635.CrossRefGoogle Scholar
  2. [2]
    Zeng, Q. Z.; Wen, H. B.; Wen, Q.; Chen, X. H.; Wang, Y. G.; Xuan, W. L.; Liang, J. S.; Wan, S. H. Cucumber mosaic virus as drug delivery vehicle for doxorubicin. Biomaterials2013, 34, 4632–4642.CrossRefGoogle Scholar
  3. [3]
    Zahorowska, B.; Crowe, P. J.; Yang, J. L. Combined therapies for cancer: A review of EGFR-targeted monotherapy and combination treatment with other drugs. J. Cancer Res. Clin. Oncol.2009, 135, 1137–1148.CrossRefGoogle Scholar
  4. [4]
    Xue, X. D.; Huang, Y.; Bo, R. N.; Jia, B.; Wu, H.; Yuan, Y.; Wang, Z. L.; Ma, Z.; Jing, D.; Xu, X. B. et al. Trojan horse nanotheranostics with dual transformability and multifunctionality for highly effective cancer treatment. Nat. Commun.2018, 9, 3653.CrossRefGoogle Scholar
  5. [5]
    Guo, L. R.; Yan, D. D.; Yang, D. F.; Li, Y. L.; Wang, X. D.; Zalewski, O.; Yan, B. F.; Lu, W. Combinatorial photothermal and immuno cancer therapy using chitosan-coated hollow copper sulfide nanoparticles. ACS Nano2014, 8, 5670–5681.CrossRefGoogle Scholar
  6. [6]
    Al-Lazikani, B.; Banerji, U.; Workman, P. Combinatorial drug therapy for cancer in the post-genomic era. Nat. Biotechnol.2012, 30, 679–692.CrossRefGoogle Scholar
  7. [7]
    Baxevanis, C. N.; Perez, S. A.; Papamichail, M. Combinatorial treatments including vaccines, chemotherapy and monoclonal antibodies for cancer therapy. Cancer Immunol., Immunother2009, 58, 317–324.CrossRefGoogle Scholar
  8. [8]
    Zhang, H.; Hollis, C. P.; Zhang, Q.; Li, T. L. Preparation and antitumor study of camptothecin nanocrystals. Int. J. Pharm.2011, 415, 293–300.CrossRefGoogle Scholar
  9. [9]
    Sun, B.; Taha, M. S.; Ramsey, B.; Torregrosa-Allen, S.; Elzey, B. D.; Yeo, Y. Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals. J. Controlled Release2016, 235, 91–98.CrossRefGoogle Scholar
  10. [10]
    Lin, Z. Q.; Gao, W.; Hu, H. X.; Ma, K.; He, B.; Dai, W. B.; Wang, X. Q.; Wang, J. C.; Zhang, X.; Zhang, Q. Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: High drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity. J. Controlled Release2014, 174, 161–170.CrossRefGoogle Scholar
  11. [11]
    Yuan, Y.; He, Y. X.; Bo, R. N.; Ma, Z.; Wang, Z. L.; Dong, L. L.; Lin, T. Y.; Xue, X. D.; Li, Y. P. A facile approach to fabricate self-assembled magnetic nanotheranostics for drug delivery and imaging. Nanoscale2018, 10, 21634–21639.CrossRefGoogle Scholar
  12. [12]
    Wang, Z. J.; Li, J.; Cho, J.; Malik, A. B. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils. Nat. Nanotechnol.2014, 9, 204–210.CrossRefGoogle Scholar
  13. [13]
    Chen, Q.; Liu, Z. Albumin carriers for cancer theranostics: A conventional platform with new promise. Adv. Mater.2016, 28, 10557–10566.CrossRefGoogle Scholar
  14. [14]
    Lovell, J. F.; Jin, C. S.; Huynh, E.; Jin, H. L.; Kim, C.; Rubinstein, J. L.; Chan, W. C. W.; Cao, W. G.; Wang, L. V.; Zheng, G. Porphysome nanovesicles generated by porphyrin bilayers for use as multimodal biophotonic contrast agents. Nat. Mater.2011, 10, 324–332.CrossRefGoogle Scholar
  15. [15]
    Mikhaylov, G.; Mikac, U.; Magaeva, A. A.; Itin, V. I.; Naiden, E. P.; Psakhye, I.; Babes, L.; Reinheckel, T.; Peters, C.; Zeiser, R. et al. Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat. Nanotechnol.2011, 6, 594–602.CrossRefGoogle Scholar
  16. [16]
    Li, Y. P.; Lin, T. Y.; Luo, Y.; Liu, Q. Q.; Xiao, W. W.; Guo, W. C.; Lac, D.; Zhang, H. Y.; Feng, C. H.; Wachsmann-Hogiu, S. et al. A smart and versatile theranostic nanomedicine platform based on nanoporphyrin. Nat. Commun.2014, 5, 4712.CrossRefGoogle Scholar
  17. [17]
    Yang, X. X.; Xue, X. D.; Luo, Y.; Lin, T. Y.; Zhang, H. Y.; Lac, D.; Xiao, K.; He, Y. X.; Jia, B.; Lam, K. S. et al. Sub-100 nm, long tumor retention SN-38-loaded photonic micelles for tri-modal cancer therapy. J. Controlled Release2017, 261, 297–306.CrossRefGoogle Scholar
  18. [18]
    Li, Y. P.; Xiao, W. W.; Xiao, K.; Berti, L.; Luo, J. T.; Tseng, H. P.; Fung, G.; Lam, K. S. Well-defined, reversible boronate crosslinked nanocarriers for targeted drug delivery in response to acidic ph values and cis-diols. Angew. Chem., Int. Ed.2012, 51, 2864–2869.CrossRefGoogle Scholar
  19. [19]
    Zhang, M.; Song, C. C.; Su, S.; Du, F. S.; Li, Z. C. Ros-activated ratiometric fluorescent polymeric nanoparticles for self-reporting drug delivery. ACS Appl. Mater. Interfaces2018, 10, 7798–7810.CrossRefGoogle Scholar
  20. [20]
    Wang, Z. L.; Xue, X. D.; He, Y. X.; Lu, Z. W.; Jia, B.; Wu, H.; Yuan, Y.; Huang, Y.; Wang, H.; Lu, H. W. et al. Novel redox-responsive polymeric magnetosomes with tunable magnetic resonance property for in vivo drug release visualization and dual-modal cancer therapy. Adv. Funct. Mater.2018, 28, 1802159.CrossRefGoogle Scholar
  21. [21]
    Xue, X. D.; Huang, Y.; Wang, X. S.; Wang, Z. L.; Carney, R. P.; Li, X. C.; Yuan, Y.; He, Y. X.; Lin, T. Y.; Li, Y. P. Self-indicating, fully active pharmaceutical ingredients nanoparticles (FAPIN) for multimodal imaging guided trimodality cancer therapy. Biomaterials2018, 161, 203–215.CrossRefGoogle Scholar
  22. [22]
    Correia, A.; Shahbazi, M. A.; Mäkilä, E.; Almeida, S.; Salonen, J.; Hirvonen, J.; Santos, H. A. Cyclodextrin-modified porous silicon nanoparticles for efficient sustained drug delivery and proliferation inhibition of breast cancer cells. ACS Appl. Mater. Interfaces2015, 7, 23197–23204.CrossRefGoogle Scholar
  23. [23]
    Sierpe, R.; Lang, E.; Jara, P.; Guerrero, A. R.; Chornik, B.; Kogan, M. J.; Yutronic, N. Gold nanoparticles interacting with β-cyclodextrin-phenylethylamine inclusion complex: A ternary system for photothermal drug release. ACS Appl. Mater. Interfaces2015, 7, 15177–15188.CrossRefGoogle Scholar
  24. [24]
    Liu, Z. H.; Jiao, Y. P.; Wang, Y. F.; Zhou, C. R.; Zhang, Z. Y. Polysaccharides-based nanoparticles as drug delivery systems. Adv. Drug Deliv. Rev.2008, 60, 1650–1662.CrossRefGoogle Scholar
  25. [25]
    Chidambaram, M.; Manavalan, R.; Kathiresan, K. Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J. Pharm. Pharm. Sci.2011, 14, 67–77.CrossRefGoogle Scholar
  26. [26]
    Cai, K. M.; He, X.; Song, Z. Y.; Yin, Q.; Zhang, Y. F.; Uckun, F. M.; Jiang, C.; Cheng, J. J. Dimeric drug polymeric nanoparticles with exceptionally high drug loading and quantitative loading efficiency. J. Am. Chem. Soc.2015, 137, 3458–3461.CrossRefGoogle Scholar
  27. [27]
    Zheng, X. H.; Li, Z. S.; Chen, L.; Xie, Z. G.; Jing, X. B. Self-assembly of porphyrin-paclitaxel conjugates into nanomedicines: Enhanced cytotoxicity due to endosomal escape. Chem.—Asian J.2016, 11, 1780–1784.CrossRefGoogle Scholar
  28. [28]
    Lu, K. D.; He, C. B.; Guo, N. N.; Chan, C.; Ni, K. Y.; Lan, G. X.; Tang, H. D.; Pelizzari, C.; Fu, Y. X.; Spiotto, M. T. et al. Low-dose X-ray radiotherapy-radiodynamic therapy via nanoscale metal-organic frameworks enhances checkpoint blockade immunotherapy. Nat. Biomed. Eng.2018, 2, 600–610.CrossRefGoogle Scholar
  29. [29]
    Yu, B.; Goel, S.; Ni, D. L.; Ellison, P. A.; Siamof, C. M.; Jiang, D. W.; Cheng, L.; Kang, L.; Yu, F. Q.; Liu, Z. et al. Reassembly of 89Zr-labeled cancer cell membranes into multicompartment membrane-derived liposomes for PET-trackable tumor-targeted theranostics. Adv. Mater.2018, 30, 1704934.CrossRefGoogle Scholar
  30. [30]
    Cheng, Y. J.; Zhang, A. Q.; Hu, J. J.; He, F.; Zeng, X.; Zhang, X. Z. Multifunctional peptide-amphiphile end-capped mesoporous silica nanoparticles for tumor targeting drug delivery. ACS Appl. Mater. Interfaces2017, 9, 2093–2103.CrossRefGoogle Scholar
  31. [31]
    Pommier, Y. Topoisomerase I inhibitors: Camptothecins and beyond. Nat. Rev. Cancer2006, 6, 789–802.CrossRefGoogle Scholar
  32. [32]
    Ragàs, X.; Jiménez-Banzo, A.; Sánchez-García, D.; Batllori, X.; Nonell, S. Singlet oxygen photosensitisation by the fluorescent probe singlet oxygen sensor green®. Chem. Commun.2009, 2920–2922.Google Scholar
  33. [33]
    Xue, X. D.; Zhao, Y. Y.; Dai, L. R.; Zhang, X.; Hao, X. H.; Zhang, C. Q.; Huo, S. D.; Liu, J.; Liu, C.; Kumar, A. et al. Spatiotemporal drug release visualized through a drug delivery system with tunable aggregation-induced emission. Adv. Mater.2014, 26, 712–717.CrossRefGoogle Scholar
  34. [34]
    Yu, Y.; Feng, C.; Hong, Y. N.; Liu, J. Z.; Chen, S. J.; Ng, K. M.; Luo, K. Q.; Tang, B. Z. Cytophilic fluorescent bioprobes for long-term cell tracking. Adv. Mater.2011, 23, 3298–3302.CrossRefGoogle Scholar
  35. [35]
    Morris, W.; Volosskiy, B.; Demir, S.; Gándara, F.; McGrier, P. L.; Furukawa, H.; Cascio, D.; Stoddart, J. F.; Yaghi, O. M. Synthesis, structure, and metalation of two new highly porous zirconium metal-organic frameworks. Inorg. Chem.2012, 51, 6443–6445.CrossRefGoogle Scholar
  36. [36]
    Liu, J.; Huang, Y. R.; Kumar, A.; Tan, A.; Jin, S. B.; Mozhi, A.; Liang, X. J. Ph-sensitive nano-systems for drug delivery in cancer therapy. Biotechnol. Adv.2014, 32, 693–710.CrossRefGoogle Scholar
  37. [37]
    Tan, S. J.; Jana, N. R.; Gao, S. J.; Patra, P. K.; Ying, J. Y. Surfaceligand-dependent cellular interaction, subcellular localization, and cytotoxicity of polymer-coated quantum dots. Chem. Mater.2010, 22, 2239–2247.CrossRefGoogle Scholar
  38. [38]
    Naim, B.; Zbaida, D.; Dagan, S.; Kapon, R.; Reich, Z. Cargo surface hydrophobicity is sufficient to overcome the nuclear pore complex selectivity barrier. EMBO J.2009, 28, 2697–2705.CrossRefGoogle Scholar
  39. [39]
    Zhou, Y.; Sun, H. J.; Wang, F. M.; Ren, J. S.; Qu, X. G. How functional groups influence the ros generation and cytotoxicity of graphene quantum dots. Chem. Commun.2017, 53, 10588–10591.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Ye Yuan
    • 1
    • 2
  • Ruonan Bo
    • 2
    • 3
  • Di Jing
    • 2
    • 4
  • Zhao Ma
    • 2
  • Zhongling Wang
    • 2
    • 5
  • Tzu-yin Lin
    • 6
  • Lijie Dong
    • 1
  • Xiangdong Xue
    • 2
    • 7
    Email author
  • Yuanpei Li
    • 2
    Email author
  1. 1.Center for Smart Materials and Devices, State Key Laboratory of Advanced Technology for Materials Synthesis and ProcessingWuhan University of TechnologyWuhanChina
  2. 2.Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer CenterUniversity of California DavisSacramentoUSA
  3. 3.School of Veterinary MedicineYangzhou UniversityYangzhouChina
  4. 4.Department of Oncology, Xiangya HospitalCentral South UniversityChangshaChina
  5. 5.Department of Radiology, Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  6. 6.Division of Hematology/Oncology, Department of Internal MedicineUniversity of California DavisSacramentoUSA
  7. 7.College of Life SciencesNorthwest UniversityXi’anChina

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