International Journal of Nanomedicine (Jul 2019)
Antitumor effect of hyaluronic-acid-modified chitosan nanoparticles loaded with siRNA for targeted therapy for non-small cell lung cancer
Abstract
Wenhua Zhang,1,2,* Wenhua Xu,1,* Yu Lan,3 Xuliang He,1 Kaibin Liu,4 Ye Liang21Department of Inspection, Medical Faculty, Qingdao University, Qingdao 266003, People’s Republic of China; 2Key Laboratory, Department of Urology and Andrology, Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of China; 3Department of Inspection, Weihai Central Hospital, Weihai 264400, People’s Republic of China; 4Department of Clinical Medicine, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workPurpose: Nanoparticle (NP)-mediated targeted delivery of therapeutic genes or siRNAs to tumors has potential advantages. In this study, hyaluronic acid (HA)-modified chitosan nanoparticles (CS NPs-HA) loaded with cyanine 3 (Cy3)-labeled siRNA (sCS NPs-HA) were prepared and characterized.Methods: Human non-small cell lung cancer (NSCLC) A549 cells expressing receptor CD44 and tumor-bearing mice were used to evaluate the cytotoxic and antitumor effects of sCS NPs-HA in vitro and in vivo.Results: The results showed that noncytotoxic CS NPs-HA of small size (100–200 nm) effectively delivered the Cy3-labeled siRNA to A549 cells via receptor CD44 and inhibited cell proliferation by downregulating the target gene BCL2. In vivo experiment results revealed that sCS NPs-HA directly delivered greater amounts of Cy3-labeled siRNA to the tumor sites, resulting in the inhibition of tumor growth by downregulating BCL2, as compared to unmodified NPs loaded with siRNA (sCS NPs) and to naked Cy3-labeled siRNA.Conclusion: The HA-modified NPs based on chitosan could serve as a promising carrier for siRNA delivery and targeted therapy for NSCLC expressing CD44.Keywords: nanoparticle, siRNA, CD44, hyaluronic acid, cancer
