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Paclitaxel nanoparticle awakens immune system to fight against cancer

Abstract

In chemotherapy, high concentration of paclitaxel (PTX) is used for anti-tumor treatment but toxic to immune cells. At lower concentration, PTX was found able to stimulate the anti-tumor potentials of immune cells. Thus, lowering down the cytotoxicity of PTX at high concentration but maintaining its anti-tumor stimulation to immune cells remains challenging. Herein, employing a click condensation reaction, we rationally designed a PTX derivative, Cys(StBu)-Arg-Arg-Arg-Lys(PTX)-CBT (1), for the facile preparation of its nanoparticle 1-NP. In vitro assays indicated that, at high PTX concentration, 1-NP showed significantly lower cytotoxicity to macrophages than PTX, could be efficiently phagocytosed by macrophages and consequently polarize the cells into an anti-tumor state in a dose-dependent manner. In vivo experiments further confirmed that 1-NP possessed higher anti-tumor efficacy than free PTX but lower cytotoxicity to immune cells in both immune organs and tumor sites. Our results suggest that, by using different dose of 1-NP, patients can precisely regulate the activation of immune system for an effective anti-tumor and balanced autoimmune responses. We also envision that our strategy could be a combined immunotherapy and chemotherapy for a more efficient anti-tumor treatment in the future.

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Publication details

The article was received on 24 Dec 2016, accepted on 13 Apr 2017 and first published on 13 Apr 2017


Article type: Paper
DOI: 10.1039/C6NR09895A
Citation: Nanoscale, 2017, Accepted Manuscript
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    Paclitaxel nanoparticle awakens immune system to fight against cancer

    W. Tang, J. Yang, Y. Yuan, Z. Zhao, Z. Lian and G. Liang, Nanoscale, 2017, Accepted Manuscript , DOI: 10.1039/C6NR09895A

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