Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation.
To identify a new drug candidate for treating endometriosis which has fewer side effects, a new polymeric nanoparticle gene delivery system consisting of polyethylenimine-grafted chitosan oligosaccharide (CSO-PEI) with hyaluronic acid (HA) and small interfering RNA (siRNA) was designed. There was no obvious difference in sizes observed between (CSO-PEI/siRNA)HA and CSO-PEI/siRNA, but the fluorescence accumulation in the endometriotic lesion was more significant for (CSO-PEI/siRNA)HA compared with CSO-PEI/siRNA due to the specific binding of HA to CD44. In addition, the (CSO-PEI/siRNA)HA nanoparticle gene therapy significantly decreased the endometriotic lesion sizes with atrophy and degeneration of the ectopic endometrium. The epithelial cells of ectopic endometrium from rat models of endometriosis showed a significantly lower CD44 expression than control after treatment with (CSO-PEI/siRNA)HA. Furthermore, observation under an electron microscope showed no obvious toxic effect on the reproductive organs. Therefore, (CSO-PEI/siRNA)HA gene delivery system can be used as an effective method for the treatment of endometriosis.
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Meng-Dan
MD
Zhao
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Jin-Lin
JL
Cheng
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Jing-Jing
JJ
Yan
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Feng-Ying
FY
Chen
Department of Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Jian-Zhong
JZ
Sheng
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Dong-Li
DL
Sun
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Jian
J
Chen
The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Jing
J
Miao
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Run-Ju
RJ
Zhang
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Cai-Hong
CH
Zheng
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
He-Feng
HF
Huang
D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006820:Hyaluronic Acid / Q000737:chemistry*; D007124:Immunoenzyme Techniques; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014591:Uterine Diseases / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
D011108:Polymers; D034741:RNA, Small Interfering; C551320:chitosan-graft-polyethylenimine; D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D048271:Chitosan
AQP2-siRNA; chitosan-PEI; endometriosis; hyaluronic acid; targeted therapy