Skip to main content
Log in

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

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  6. Al-Lazikani, B.; Banerji, U.; Workman, P. Combinatorial drug therapy for cancer in the post-genomic era. Nat. Biotechnol.2012, 30, 679–692.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  13. Chen, Q.; Liu, Z. Albumin carriers for cancer theranostics: A conventional platform with new promise. Adv. Mater.2016, 28, 10557–10566.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  25. Chidambaram, M.; Manavalan, R.; Kathiresan, K. Nanotherapeutics to overcome conventional cancer chemotherapy limitations. J. Pharm. Pharm. Sci.2011, 14, 67–77.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  31. Pommier, Y. Topoisomerase I inhibitors: Camptothecins and beyond. Nat. Rev. Cancer2006, 6, 789–802.

    Article  CAS  Google Scholar 

  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. 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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xiangdong Xue or Yuanpei Li.

Electronic Supplementary Material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yuan, Y., Bo, R., Jing, D. et al. Excipient-free porphyrin/SN-38 based nanotheranostics for drug delivery and cell imaging. Nano Res. 13, 503–510 (2020). https://doi.org/10.1007/s12274-020-2641-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-020-2641-z

Keywords

Navigation