4.8 Article

Clickable amino acid tuned self-assembly of a nucleus-selective multi-component nanoplatform for synergistic cancer therapy

Journal

CHEMICAL SCIENCE
Volume 12, Issue 24, Pages 8394-8400

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/d1sc01073e

Keywords

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Funding

  1. National Natural Science Foundation of China [21773268, 21877010]
  2. Fundamental Research Funds for the Central Universities [2019CDYGYB006]
  3. Chongqing Graduate Student Research Innovation Project [CYB18056, CYB19067]
  4. Startup Funding of Chongqing University [0236011104419]

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This study presents a nucleus-targeted synergistic chemo-photodynamic therapy using the self-assembly of chlorin e6 (Ce6) and doxorubicin (DOX), which demonstrates enhanced cellular uptake and accumulation in the nucleus, leading to improved therapeutic efficacy for cancer treatment. The introduction of clickable dibenzocyclooctyne (DIBO) functionalized lysine (D-K) and crosslinkers enables efficient self-assembly of the nanodrugs, showing great potential for nucleus-specific drug delivery strategies.
Nucleus-targeted therapy holds great promise in cancer treatment; however, a lack of effective nucleus-specific delivery significantly limits its application potential. Here, we report a nucleus-targeted synergistic chemo-photodynamic therapy based on the self-assembly of chlorin e6 (Ce6) and doxorubicin (DOX) tuned by clickable dibenzocyclooctyne (DIBO) functionalized lysine (D-K) and subsequent reaction with crosslinkers. The assembled nanodrugs with high loading efficiency and long-term stability show enhanced cellular uptake and accumulation in the nucleus, resulting in greatly improved in vitro and in vivo chemo-photodynamic efficacy. Notably, D-K can promote the rapid self-assembly of Ce6 and DOX in aqueous solution, avoiding the introduction of organic solvents or tedious preparations. In addition, the introduction of the DIBO group can effectively expand the types of self-assembly material and enhance the self-assembly behaviour through a copper-free click reaction. Therefore, we present an effective nucleus-targeted combination drug delivery strategy, which has great potential in the treatment of many diseases.

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