Abstract
A type of sorafenib- (SOR-) loaded long-circulating nanoliposome was constructed, and the targeting performance and antitumor effects of the prepared liposome were evaluated in the present study. Polyethylene glycol- (PEG-) modified long-circulating nanoliposomes (LC-NPs) were designed and prepared using reverse evaporation, and the LC-NPs were used for delivering sorafenib (LC-PEG-SOR-NPs). Then, the anti-VEGFR antibody as a targeting moiety was chemically coupled with LC-PEG-SOR-NPs to form liver cancer-targeted nanoliposomes (anti-VEGFR-LC-PEG-SOR-NPs). The drug entrapment and loading efficiency were measured. And the cancer-targeting performance and therapeutic efficiency were evaluated both in vitro and in vivo. The anti-VEGFR-LC-PEG-SOR-NPs with an average of 119.8 ± 4.2 nm showed a uniform spherical structure. The drug entrapment and loading efficiency were 92.5% and 18.5%, respectively. The killing efficiency of anti-VEGFR-LC-PEG-SOR-NPs was up to 18% after incubating with liver cancer cells for 72 h. Furthermore, the anti-VEGFR-LC-PEG-SOR-NPs could actively target at the tumor region and could efficiently inhibit tumor growth with negligible side effects. This newly designed nanoliposomes had desirable dispersibility, high drug entrapment efficiency, tumor targeting and therapeutic efficiency, and good safety. As a biocompatible nanocomposite, it was promising to become a novel and useful tumor-targeting nanodrug for liver cancer therapy.
Highlights
As the sixth most common tumor worldwide, liver cancer ranks the third in cancer mortality, while 80% of patients were diagnosed in developing countries, and 44% were in China [1, 2]
Our results showed that anti-vascular endothelial growth factor receptor (VEGFR)-LC-Polyethylene glycol- (PEG-)SOR-NPs had good specificity and affinity for tumor cells, and the liposomes were expected to become a novel type of antitumor drug carrier
Experimental SPFlevel Balb/c-nu mice were purchased from Shanghai Slack Laboratory Animal Co., Ltd.; DMEM medium, fetal bovine serum, and trypsin were purchased from Gibco; VEGFR antibody was purchased from eBioscience; DSPE-PEG was obtained from Avanti, USA; carboxymethyl chitosan cetyl quaternary ammonium salt (HQCMC), Prussian blue staining kit were purchased from Solarbio; 1,2-dioleoylphosphatidylcholine (DOPC), dimethyl octadecyl epoxypropyl ammonium chloride (GHDC), cholesterol, dichloromethane, N-hydroxysuccinimide (NHS), 1-ethyl-3-(3-dimethyl ammonium propyl) ammonium bicarbonate (EDC), and other commonly used reagents were purchased from Sinopharm; and cholesterol (Chol), dichloromethane, and other commonly used reagents were purchased from Sinopharm Group
Summary
As the sixth most common tumor worldwide, liver cancer ranks the third in cancer mortality, while 80% of patients were diagnosed in developing countries, and 44% were in China [1, 2]. Diagnosis and surgical treatment are the best option to manage liver cancer. Only 20% to 30% of liver cancer patients can be diagnosed early according to the statistical data [3, 4]. Most patients in the middle and late stages have to choose chemotherapy, radiotherapy, and interventional therapy, but those chemical drugs damage normal liver tissues [5, 6]. How to improve the targeting effect of drugs for liver cancer cells, extend the effective time of drugs, and reduce the damage to normal tissues has become a research hotspot. Based on the existing findings, targeted therapy plays an important role in patients with advanced liver cancer, such as targeted therapy with sorafenib (SOR) [14]. Sorafenib inhibits the RAS/RAF/MEK/ERK signaling pathway by inhibiting the activity of RAF, thereby directly suppresses
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