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Adaptive Immune Cells are Necessary for the Enhanced Therapeutic Effect of Sorafenib-Loaded Nanoparticles

Abstract

Sorafenib is a kinase inhibitor approved for treatment of primary kidney cancer, advanced primary liver cancer, and radioactive iodine resistant advanced thyroid carcinoma. However, sorafenib usually caused serious side effects, which limited its antitumor effect. Nanoparticle based drug delivery systems have been widely used to enhance the therapeutic effects and reduce the side effects of drug by the enhanced permeability and retention (EPR) effect. Herein, to improve the therapeutic effect of sorafenib, we developed the poly (ethylene glycol)-b-poly (lactic acid-co-glycolic acid) (PEG-PLGA) based nanoparticles by dialysis method for sorafenib encapsulation. After intravenous injection of the sorafenib loaded nanoparticles (NPsorafenib), the tumor growth of mice bearing B16-F10, MC38 and LLC tumor was significantly inhibited. Meanwhile, the dose of sorafenib was reduced to one ninth and side effects on the hematopoietic system and immune system were abrogated. More importantly, the tumor growth inhibition effect of NPsorafenib was dramatically reduced in B16-F10 bearing Rag1-/- mice which are adaptive immune cells defective, indicating that the antitumor effects of NPsorafenib is dependent on the adaptive immune cells (Scheme 1). These results emphasize the indispensable role of adaptive immune system in nano-drug mediated antitumor effects and adaptive immune system should be considered as an important factor for clinical applications.

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Publication details

The article was received on 27 Jan 2018, accepted on 12 Feb 2018 and first published on 15 Feb 2018


Article type: Paper
DOI: 10.1039/C8BM00106E
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Adaptive Immune Cells are Necessary for the Enhanced Therapeutic Effect of Sorafenib-Loaded Nanoparticles

    Z. Lian, Z. Zhao, J. Long, Y. Zhao, J. Yang, W. Jiang, Q. Liu, K. Yan, L. Li and Y. Wang, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00106E

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