title: 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.
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Shuyan
authors.initials: S
authors.lastname: Liang
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D003596:Cytosine; D016503:Drug Delivery Systems / Q000379:methods*; D006147:Guanine; D006801:Humans; D007097:Imines / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics / Q000628:therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D054118:Nanospheres / Q000008:administration & dosage* / Q000737:chemistry; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011095:Polyethylenes / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000180:Acrylic Resins; D000970:Antineoplastic Agents; C423449:CpG ODN 1826; D007097:Imines; D009838:Oligodeoxyribonucleotides; D011095:Polyethylenes; D011137:Polystyrenes; D011720:Pyrazoles; D011804:Quinolines; D018125:Receptors, Transforming Growth Factor beta; C505405:poly(ethylene imine); C555360:poly(styrene-co-acrylamide); D006147:Guanine; C557799:LY-2157299; D003596:Cytosine; D011094:Polyethyleneimine; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I
keywords: CpG; Pst-AAm copolymer nanosphere; TGF-β receptor I inhibitor; immunotherapy