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

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.

Keywords:

• CpG
• TGF-β receptor I inhibitor
• Pst-AAm copolymer nanosphere
• immunotherapy

Supplementary materials

Figure S1 Release of LY.

Note: In total, 10.6% LY was released within 24 hours, after which it was released slowly.

Abbreviation: LY, LY215729.

Figure S2 Comparison of Masson’s trichrome staining of tumor tissues under different treatments.

Note: Collagen fibers (blue) were rich in the PBS group and poor in other groups.

Abbreviations: PBS, phosphate-buffered saline; PS, polyethylenimine-modified carboxyl-styrene/acrylamide; LY, LY215729; CpG, cytosine-phosphate-guanine.

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (81573013) and the grant from National Basic Research Program of China (973 Program, 2012CB932500). We are thankful to the Analysis and Test Center of Huazhong University of Science and Technology.

Disclosure

The authors report no conflicts of interest in this work.