Self-Synthesizing Nanorods from Dynamic Combinatorial Libraries against Drug Resistant Cancer

Yu Cao, Jian Yang, Dominik Eichin, Fangzhe Zhao, Dawei Qi, Laura Kahari, Chunman Jia, Markus Peurla, Jessica M. Rosenholm, Zhao Zhao, Sirpa Jalkanen, Jianwei Li

Research output: Contribution to journalArticleScientificpeer-review

1 Citation (Scopus)

Abstract

Molecular self-assembly has been widely used to develop nanocarriers for drug delivery. However, most of them have unsatisfactory drug loading capacity (DLC) and the dilemma between stimuli-responsiveness and stability, stagnating their translational process. Herein, we overcame these drawbacks using dynamic combinatorial chemistry. A carrier molecule was spontaneously and quantitatively synthesized, aided by co-self-assembly with a template molecule and an anti-cancer drug doxorubicin (DOX) from a dynamic combinatorial library that was operated by disulfide exchange under thermodynamic control. The highly selective synthesis guaranteed a stable yet pH- and redox- responsive nanocarrier with a maximized DLC of 40.1?% and an enhanced drug potency to fight DOX resistance in vitro and in vivo. Our findings suggested that harnessing the interplay between synthesis and self-assembly in complex chemical systems could yield functional nanomaterials for advanced applications.
Original languageEnglish
Pages (from-to)3062-3070
Number of pages10
JournalAngewandte Chemie International Edition
Volume60
Issue number6
DOIs
Publication statusPublished - 8 Feb 2021
MoE publication typeA1 Journal article-refereed

Keywords

  • cancer drug resistance
  • drug delivery
  • dynamic combinatorial chemistry
  • self-assembly
  • systems chemistry

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