Poly(ester amine)-mediated, aerosol-delivered Akt1 small interfering RNA suppresses lung tumorigenesis.
BACKGROUND
The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for the development of novel therapeutic options. Recent advances in aerosol-mediated gene delivery have provided the possibility of an alternative for the safe and effective treatment of lung cancer.


OBJECTIVE
To demonstrate the feasibility and emphasize the importance of noninvasive aerosol delivery of Akt1 small interfering RNA (siRNA) as an effective and selective option for lung cancer treatment.


METHODS
Nanosized poly(ester amine) polymer was synthesized and used as a gene carrier. An aerosol of poly(ester amine)/Akt1 siRNA complex was delivered into K-ras(LA1) and urethane-induced lung cancer models through a nose-only inhalation system. The effects of Akt1 siRNA on lung cancer progression and Akt-related signals were evaluated.


RESULTS
The aerosol-delivered Akt1 siRNA suppressed lung tumor progression significantly through inhibiting Akt-related signals and cell cycle.


CONCLUSIONS
The use of poly(ester amine) serves as an effective carrier, and aerosol delivery of Akt1 siRNA may be a promising approach for lung cancer treatment and prevention.
Xu
Cheng-Xiong
CX
Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Korea.
Jere
Dhananjay
D
Jin
Hua
H
Chang
Seung-Hee
SH
Chung
Youn-Sun
YS
Shin
Ji-Young
JY
Kim
Ji-Eun
JE
Park
Sung-Jin
SJ
Lee
Yong-Hoon
YH
Chae
Chan-Hee
CH
Lee
Kee Ho
KH
Beck
George R
GR
Cho
Chong-Su
CS
Cho
Myung-Haing
MH
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D002273:Carcinogens; D018797:Cell Cycle Proteins / Q000378:metabolism; D004337:Drug Carriers; D011905:Genes, ras; D015316:Genetic Therapy; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D053761:Nanocomposites; D011073:Polyamines; D011091:Polyesters; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D014162:Transfection; D014520:Urethane
D000336:Aerosols; D002273:Carcinogens; D018797:Cell Cycle Proteins; D004337:Drug Carriers; D011073:Polyamines; D011091:Polyesters; D034741:RNA, Small Interfering; C516446:poly(caprolactone-block-ethyleneimine); D014520:Urethane; D051057:Proto-Oncogene Proteins c-akt