A polyethylenimine-modified carboxyl-poly(styrene/acrylamide) copolymer nanosphere for co-delivering of CpG and TGF-β receptor I inhibitor with remarkable additive tumor regression effect against liver cancer in mice

一种聚乙烯亚胺修饰的羧基聚(苯乙烯/丙烯酰胺)共聚物纳米球,可共递送CpG和TGF-β受体I抑制剂,对小鼠肝癌具有显著的叠加肿瘤消退效果。

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Abstract

Cancer immunotherapy based on nanodelivery systems has shown potential for treatment of various malignancies, owing to the benefits of tumor targeting of nanoparticles. However, induction of a potent T-cell immune response against tumors still remains a challenge. In this study, polyethylenimine-modified carboxyl-styrene/acrylamide (PS) copolymer nano-spheres were developed as a delivery system of unmethylated cytosine-phosphate-guanine (CpG) oligodeoxynucleotides and transforming growth factor-beta (TGF-β) receptor I inhibitors for cancer immunotherapy. TGF-β receptor I inhibitors (LY2157299, LY) were encapsulated to the PS via hydrophobic interaction, while CpG oligodeoxynucleotides were loaded onto the PS through electrostatic interaction. Compared to the control group, tumor inhibition in the PS-LY/CpG group was up to 99.7% without noticeable toxicity. The tumor regression may be attributed to T-cell activation and amplification in mouse models. The results highlight the additive effect of CpG and TGF-β receptor I inhibitors co-delivered in cancer immunotherapy.

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