pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery.
Combination of chemotherapeutic drug and small interfering RNA (siRNA) can affect multiple disease pathways and has been proven effective in suppressing tumor progression. Co-delivery of drug and siRNA within a same nanocarrier is a vital means in this field. The present study aimed at the development of a pH-sensitive liposome to co-deliver drug and siRNA to tumor region. Driven by the electrostatic interaction, the pH-sensitive material, carboxymethyl chitosan (CMCS), was coated onto the surface of the cationic liposome (CL) preloaded with sorafenib (Sf) and siRNA (Si). To evaluate whether the resulting CMCS-modified Sf and siRNA co-delivery cationic liposome (CMCS-SiSf-CL) enhanced antitumor efficiency after systematic administration, in vitro and in vivo experiments were evaluated in HepG2 cells and the H22 cells-bearing Kunming mice model. The experimental results demonstrated that CMCS-SiSf-CL was able to condense siRNA efficiently and protect siRNA from being degraded by serum and RNase. The release rate of Sf from CMCS-modified liposome exhibited pH-sensitive release behavior. Furthermore, in vitro cellular uptake results showed that CMCS-SiSf-CL yielded higher fluorescence intensity at pH 6.5 than at pH 7.4, and that siRNA could be delivered to tumor site by CMCS-SiSf-CL in vivo. The in vivo antitumor efficacy showed that CMCS-Sf-CL inhibits tumor growth effectively when compared with free Sf solution. In current experimental conditions, this liposomal formulation did not show significant toxicity both in vitro and in vivo. Therefore, co-delivering Sf with siRNA by CMCS-SiSf-CL might provide a promising approach for tumor therapy.
School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People's Republic of China.
Yao
Y
Yao
School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People's Republic of China.
Zhihui
Z
Su
School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People's Republic of China.
Yanchao
Y
Liang
School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong, People's Republic of China.
Na
N
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D002412:Cations / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D000077157:Sorafenib
D000970:Antineoplastic Agents; D002412:Cations; D008081:Liposomes; D010671:Phenylurea Compounds; D034741:RNA, Small Interfering; C514968:carboxymethyl-chitosan; D009536:Niacinamide; D048271:Chitosan; D000077157:Sorafenib
cancer therapy; charge conversion; co-delivery; gene; sorafenib