Aerosol delivery of folate-decorated hyperbranched polyspermine complexes to suppress lung tumorigenesis via Akt signaling pathway.
Lung cancer has been a leading cause of cancer mortality worldwide and aerosol-mediated gene therapy endows numerous advantages compared to other traditional modalities. Here, we reported a folic acid (FA)-modified hyperbranched polyspermine (HPSPE) with prominent biocompatibility for lung cancer cell targeted gene therapy. FA was decorated to the HPSPE via an amidation reaction and the physicochemical properties of nanoplexes formed with DNA were characterized. Gel electrophoresis study elucidated that the designed polymer was capable to condense DNA and protect it from degradation by DNase I. Cell viability and transfection efficiency assay in vitro and in vivo indicated its increased transfection performance with lower toxicity. Furthermore, reduced tumor numbers and down-regulation of Akt1 protein after aerosol treatment containing FA-HPSPE/shAkt1 complexes proved its therapeutic potential for lung cancer suppression. Results obtained in this study suggested that FA-HPSPE with highly biocompatibility and targeting capability while forming complexes with shAkt1 and administrated through noninvasive aerosol could be prospective for inhibiting lung tumorigenesis.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Cheng-Qiong
CQ
Luo
Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Yoonjeong
Y
Jang
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Lei
L
Xing
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Peng-Fei
PF
Cui
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
Jian-Bin
JB
Qiao
Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Ah Young
AY
Lee
Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Hyeon-Jeong
HJ
Kim
Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea. Electronic address: mchotox@snu.ac.kr.
Myung-Haing
MH
Cho
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, China. Electronic address: jianghulin3@163.com.
Hu-Lin
HL
Jiang
D000336:Aerosols; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D058972:Folic Acid Transporters / Q000235:genetics; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy; D008297:Male; D008810:Mice, Inbred C57BL; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013096:Spermine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000336:Aerosols; D000970:Antineoplastic Agents; D058972:Folic Acid Transporters; D049452:Green Fluorescent Proteins; D013096:Spermine; D004247:DNA; D005492:Folic Acid; D051057:Proto-Oncogene Proteins c-akt
Aerosol delivery; Biocompatibility; Cancer cell targeting; Gene therapy; Lung cancer; shAkt1