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Enhanced Prevention of Breast Tumor Metastasis by Nanoparticle‐Delivered Vitamin E in Combination with Interferon‐Gamma
Author(s) -
Wu Yilun,
Liu Jianping,
Movahedi Fatemeh,
Gu Wenyi,
Xu Tiefeng,
Xu Zhi Ping
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201901706
Subject(s) - combination therapy , cancer research , metastasis , cancer cell , cytotoxic t cell , pharmacology , apoptosis , tumor microenvironment , chemistry , medicine , cancer , biochemistry , tumor cells , in vitro
Preventing cancer metastasis is one of the remaining challenges in cancer therapy. As an efficient natural product, alpha‐tocopheryl succinate (α‐TOS), the most effective form of vitamin E, holds great anticancer potential. To improve its efficacy and bioavailability, lipid‐coated calcium carbonate/phosphate (LCCP) nanoparticles (NPs) with folic acid and PEG modification are synthesized for efficient delivery of α‐TOS to 4T1 cancer cells. The optimized LCCP‐FA NPs (NP‐TOS15) show an α‐TOS loading efficiency of around 60%, and enhanced uptake by 4T1 metastatic cancer cells. Consequently, NP‐TOS15 significantly enhance the anticancer effect in combination with interferon‐gamma (IFN‐γ) in terms of apoptosis facilitation and migration inhibition. Importantly, NP‐TOS15 upregulate the anticancer immunity via downregulating program death ligand 1 (PD‐L1) expression that is initially induced by IFN‐γ, and remarkably prevent the lung metastasis, particularly in combination with IFN‐γ. Further investigation reveals that this combination therapy also modulates the cytotoxic lymphocyte infiltration into the tumor microenvironment for tumor elimination. Taken together, the NP delivery of α‐TOS in combination with IFN‐γ provides an applicable strategy for cancer therapy.