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

Nanoscale
Zhengze LuQin He

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 simult...Continue Reading

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Citations

Feb 17, 2019·AAPS PharmSciTech·Tori CzechMoses O Oyewumi
Jan 1, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jing-Bo MaXiao-Li Zhang
Aug 13, 2021·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Martina CapozzaSilvio Aime
Aug 11, 2021·Pharmaceutics·Elham RastegariYueh Chien
Aug 19, 2020·ACS Applied Materials & Interfaces·Zipeng ZhangNa Zhang
Sep 4, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zhengze LuQin He

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Methods Mentioned

BETA
nuclear translocation
xenograft
flow cytometry
transmission electron microscopy
ELISA
protein assay

Software Mentioned

Excel
GraphPad
GraphPad Prism

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