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Issue 21, 2018
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A size-shrinkable nanoparticle-based combined anti-tumor and anti-inflammatory strategy for enhanced cancer therapy

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Abstract

Cancer-related inflammation can promote tumorigenesis, tumor growth and tumor metastasis in many types of cancers. Therefore, inhibiting cancer-related inflammation significantly improves cancer therapy. It has been reported that metformin (MET) inhibits the nuclear translocation of nuclear factor-κB (NF-κB), a key factor in cancer-related inflammation. However, the short half-life and the lack of tumor targeting limit the anti-inflammatory efficacy of MET in vivo. Herein, using pH-sensitive imine bonds, MET and the chemotherapy drug doxorubicin (DOX) were loaded onto size-shrinkable RGD-DGL-GNP nanoparticles (RDG NPs) for combination therapy. The RGD-MET-DGL-GNP nanoparticles (RMDG NPs) penetrated deep into the tumor to deliver MET and inhibit the NF-κB activity in tumor cells, which further decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expressions in tumor tissues and suppressed tumor cell proliferation. As a result, the co-administration of RGD-DOX-DGL-GNP (RDDG NPs) and RMDG NPs induced an improved therapeutic effect in a xenograft tumor model and a lipopolysaccharide (LPS)-induced pulmonary metastasis model with murine 4T1 breast cancer and CT26 colon cancer cells. Combining RDDG and RMDG NPs to simultaneously target tumors and cancer-related inflammation is a very effective anti-cancer strategy.

Graphical abstract: A size-shrinkable nanoparticle-based combined anti-tumor and anti-inflammatory strategy for enhanced cancer therapy

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Supplementary files

Article information


Submitted
09 Feb 2018
Accepted
20 Apr 2018
First published
26 Apr 2018

Nanoscale, 2018,10, 9957-9970
Article type
Paper

A size-shrinkable nanoparticle-based combined anti-tumor and anti-inflammatory strategy for enhanced cancer therapy

Z. Lu, Y. Long, X. Cun, X. Wang, J. Li, L. Mei, Y. Yang, M. Li, Z. Zhang and Q. He, Nanoscale, 2018, 10, 9957
DOI: 10.1039/C8NR01184B

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