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• W2890796276 abstract "Given that vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), over-expressed in breast cancer cells and M2-like tumor-associated macrophages (M2-TAMs) within tumor microenvironment (TME), work synergistically and independently in mediating tumor progression and immunosuppression, combinatorial immune-based approaches targeting them are expected to be a potent therapeutic modality for patients. Here, polyethylene glycol (PEG) and mannose doubly modified trimethyl chitosan (PEG = MT) along with citraconic anhydride grafted poly (allylamine hydrochloride) (PC)-based nanoparticles (NPs) (PEG = MT/PC NPs) with dual pH-responsiveness were developed to deliver VEGF siRNA (siVEGF)/PIGF siRNA (siPIGF) to both M2-TAMs and breast cancer cells for antitumor immunotherapy. With prolonged blood circulation and intelligent pH-sensitivity, PEG = MT/PC NPs were highly accumulated in tumor tissues and then internalized in M2-TAMs and breast cancer cells via mannose-mediated active targeting and passive targeting, respectively. With the charge-reversal of PC, PEG = MT/PC NPs presented effective endosomal/lysosomal escape and intracellular siRNA release, resulting in efficient gene silencing. Due to the synergism between siVEGF and siPIGF in anti-proliferation of tumor cells and reversal of the TME from pro-oncogenic to anti-tumoral, PEG = MT/PC/siVEGF/siPIGF NPs (PEG = MT/PC/siV-P NPs) exerted robust suppression of breast tumor growth and lung metastasis. This combination strategy may provide a promising alternative for breast cancer therapy." @default.
• W2890796276 created "2018-09-27" @default.
• W2890796276 creator A5036164745 @default.
• W2890796276 creator A5038749396 @default.
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• W2890796276 date "2018-12-01" @default.
• W2890796276 modified "2023-10-17" @default.
• W2890796276 title "Combination antitumor immunotherapy with VEGF and PIGF siRNA via systemic delivery of multi-functionalized nanoparticles to tumor-associated macrophages and breast cancer cells" @default.
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• W2890796276 doi "https://doi.org/10.1016/j.biomaterials.2018.09.017" @default.
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