Apatinib and gamabufotalin co-loaded lipid/Prussian blue nanoparticles for synergistic therapy to gastric cancer with metastasis
Binlong Chen, Yanzhong Zhao, Zichang Lin, Jiahao Liang, Jialong Fan, Yanyan Huang, Leye He, Bin Liu
Abstract
Due to the non-targeted release and low solubility of anti-gastric cancer agent, apatinib (Apa), a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects, as well. In order to avoid these drawbacks, lipid-film-coated Prussian blue nanoparticles (PB NPs) with hyaluronan (HA) modification was used for Apa loading to improve its solubility and targeting ability. Furthermore, anti-tumor compound of gamabufotalin (CS-6) was selected as a partner of Apa with reducing dosage for combinational gastric therapy. Thus, HA-Apa-Lip@PB-CS-6 NPs were constructed to synchronously transport the two drugs into tumor tissue. In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating VEGFR and MMP-9. In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs administration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects. In summary, we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer (GC) therapy.