Synthesis of Doxorubicin and miRNA Stimuli-Sensitive Conjugates for Combination Therapy

  • Daniel F. Costa
  • Can Sarisozen
  • Vladimir P. TorchilinEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1974)


Recent advances in combination therapy by using chemotherapeutic drugs and small noncoding RNAs have highlighted the need for optimization of such agents to allow their carriage in a single delivery system. This protocol details the synthesis of a doxorubicin prodrug, where a NHS coupling reaction was used to sensitize the drug to the proteolytic activity of tumor microenvironments. The design of a lipid-modified miRNA by an S-S coupling reaction is also described. Modification of both, doxorubicin and miRNA, facilitated their simultaneous incorporation into mixed micelles for use in combination therapy against tumor cells.


Doxorubicin miRNA Prodrug Stimuli-sensitive Micelles 



This work was supported by the NIH Grant (1R21CA179286) to V. P. Torchilin and CAPES Foundation Scholarship (BEX 13275/13-5) to D. F. Costa. The authors thank Dr. W. Hartner for helpful comments on the preparation of the manuscript and Dr. R. W. Giese and Dr. P. Wang for assistance on the mass spectrometry analysis.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Daniel F. Costa
    • 1
    • 2
  • Can Sarisozen
    • 1
  • Vladimir P. Torchilin
    • 1
    Email author
  1. 1.Center for Pharmaceutical Biotechnology and NanomedicineNortheastern UniversityBostonUSA
  2. 2.CAPES Foundation, Ministry of Education of BrazilBrasíliaBrazil

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