Polyamine metabolism-based dual functional gene delivery system to synergistically inhibit the proliferation of cancer.
Polyamine content, which is associated with tumor growth, can be regulated by ornithine decarboxylase (ODC) and S-adenosyl methionine decarboxylase (SAMDC), two key enzymes in polyamine biosynthesis. Here we aim to develop a pH-responsive cationic poly(agmatine) based on a polyamine analogue-agmatine that can dually function as a gene delivery vector as well as an anticancer agent by inhibiting ODC after intracellular degradation. The core-shell nanoparticles, formed by poly(agmatine)/SAMDC siRNA complex as a core, were coated with bovine serum albumin for better in vivo circulation stability and tumor targeting. When the nanoparticles were taken up by tumor cells via endocytosis and degraded in endosome, the released agmatine and SAMDC siRNA can synergistically inhibit polyamines biosynthesis, inducing inhibition of tumor proliferation. Our study offered a potential way in tumor therapy based on polyamine metabolism.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Peng-Fei
PF
Cui
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Lei
L
Xing
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Jian-Bin
JB
Qiao
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Jia-Liang
JL
Zhang
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Yu-Jing
YJ
He
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Mei
M
Zhang
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Jin-Yuan
JY
Lyu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Cheng-Qiong
CQ
Luo
School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Liang
L
Jin
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China; Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: jianghulin3@163.com.
Hu-Lin
HL
Jiang
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry
D000970:Antineoplastic Agents; D011073:Polyamines; D034741:RNA, Small Interfering; D012710:Serum Albumin, Bovine; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase
Agmatine; Gene therapy; Polyamine metabolism; siRNA delivery