Tumor stimulus-responsive biodegradable diblock copolymer conjugates as efficient anti-cancer nanomedicines

Vladimír Šubr, Robert Pola, Shanghui Gao, Rayhanul Islam, Takuma Hirata, Daiki Miyake, Kousuke Koshino, Jian Rong Zhou, Kazumi Yokomizo, Jun Fang*, Tomáš Etrych*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Biodegradable nanomedicines are widely studied as candidates for the effective treatment of various cancerous diseases. Here, we present the design, synthesis and evaluation of biodegradable polymer-based nanomedicines tailored for tumor-associated stimuli-sensitive drug release and polymer system degradation. Diblock polymer systems were developed, which enabled the release of the carrier drug, pirarubicin, via a pH-sensitive spacer allowing for the restoration of the drug cytotoxicity solely in the tumor tissue. Moreover, the tailored design enables the matrix-metalloproteinases-or reduction-driven degradation of the polymer system into the polymer chains excretable from the body by glomerular filtration. Diblock nanomedicines take advantage of an enhanced EPR effect during the initial phase of nanomedicine pharmacokinetics and should be easily removed from the body after tumor microenvironment-associated biodegradation after fulfilling their role as a drug carrier. In parallel with the similar release profiles of diblock nanomedicine to linear polymer conjugates, these diblock polymer conjugates showed a comparable in vitro cytotoxicity, intracellular uptake, and intratumor penetration properties. More importantly, the diblock nanomedicines showed a remarkable in vivo anti-tumor efficacy, which was far more superior than conventional linear polymer conjugates. These findings suggested the advanced potential of diblock polymer conjugates for anticancer polymer therapeutics.

Original languageEnglish
Article number698
JournalJournal of Personalized Medicine
Issue number5
Early online date27 Apr 2022
Publication statusPublished - May 2022
Externally publishedYes

Bibliographical note

Funding Information:
Funding: This research was supported by the Ministry of Education, Youth and Sports of the Czech Republic within the Interexcellence program [project LTAUSA18083], from the Academy of Sciences of Czech Republic (grant no. JSPS-22-01) and Japan-Czech Republic Research Cooperative Program (JSPS) for J. Fang.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • anticancer
  • diblock conjugate
  • drug delivery
  • HPMA conjugate
  • pirarubicin

ASJC Scopus subject areas

  • Medicine (miscellaneous)


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