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Low molecular weight heparin based reduction sensitive nanoparticles for antitumor and anti-metastasis of orthotopic breast cancer

Abstract

Tumor metastasis has become a major obstacle for the clinical treatment of malignant breast cancer. Thus, a delivery system capable of both antitumor and anti-metastasis efficacy is desired. In this work, a low molecular weight heparin (LMWH) based reduction sensitive delivery system was developed, aiming to combine the properties of both the antitumor drug and active excipients to achieve a synergistic antitumor and anti-metastatic efficiency as well as resolving the potential adverse effects of both doxorubicin and LMWH. That is, the efficiency of DOX could be enhanced and its toxicity could be lowered. Meanwhile, the biological properties of LMWH could be strengthened and its bleeding risk could also be alleviated. Briefly, drug-loaded crosslinked nanoparticles (DOX/cLLHC2) had longer blood circulation time and exhibited rapid reduction-triggered release of DOX. The in vitro assays revealed DOX/cLLHC2 exhibited higher cellular uptake and cytotoxicity compared to free DOX. Meanwhile, for the existence of LMWH, DOX/cLLHC2 inhibited cell migration and invasion, as well as effectively inhibited tube-like formation of human umbilical vein endothelial cells. DOX/cLLHC2 possessed a superior tumor accumulation compared to lipoic acid unmodified nanoparticles and free DOX. Also, DOX/cLLHC2 exhibited encouraging antitumor and anti-metastasis efficiency in an orthotopic breast cancer model. Overall, DOX/cLLHC2 could exert antitumor, anti-metastasis and anti-angiogenesis efficacy simultaneously as well as lower systemic toxicity, which is suitable for the therapy of metastatic breast carcinoma.

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Publication details

The article was received on 03 May 2018, accepted on 07 Jun 2018 and first published on 13 Jun 2018


Article type: Paper
DOI: 10.1039/C8BM00486B
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Low molecular weight heparin based reduction sensitive nanoparticles for antitumor and anti-metastasis of orthotopic breast cancer

    H. Sun, D. Cao, Y. Liu, H. Wang, X. Ke and T. Ci, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00486B

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