4.7 Article

Dendron-polymer hybrid mediated anticancer drug delivery for suppression of mammary cancer

Journal

JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
Volume 63, Issue -, Pages 115-123

Publisher

JOURNAL MATER SCI TECHNOL
DOI: 10.1016/j.jmst.2020.02.089

Keywords

Polymer-drug conjugate; Dendrimers; Hybrid; Stimuli-responsive; Drug delivery system; Cancer therapy

Funding

  1. National Natural Science Foundation of China [51673127, 51873120, 81621003, 81801820]
  2. Department of Science and Technology of Sichuan Province [2018HH0006]
  3. Ministry of Science and Technology of the People's Republic of China [2015DFE52780]
  4. China Postdoctoral Science Foundation [2018M643493]
  5. 1.3.5 Research Funds in West China Hospital of Sichuan University [ZYGD18028]
  6. Fundamental Research Funds for the Central Universities [2018SCU12032]

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Dendron-polymer-based nanoscale drug delivery systems show promise in tumor targeting with low toxicity. The dendronized polymer-doxorubicin hybrid displays improved drug delivery efficiency and pH-responsive drug release, resulting in enhanced therapeutic efficacy and longer blood circulation time in cancer therapy. The biosafety and enhanced therapeutic effects of the dendronized polymer-DOX hybrid make it a promising approach for drug delivery.
Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity. Here we report a dendronized polymer-doxorubicin (DOX) hybrid (DPDH) with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate (LPDC). The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4. DPDH efficiently enters 4T1 cells and releases DOX to induce cytotoxicity and apoptosis. Owing to the dendronzied structure, DPDH has a significantly longer blood circulation time than LPDC. DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4T1 mammary cancer model than LPDC as well as free drug, evidenced from tumor growth inhibition, TUNEL assessment and histological analysis. Biosafety of DPDH is also confirmed from hemolysis, body weight shifts during treatment and pathological analysis. This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery. (C) 2020 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology.

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