Abstract
Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL−1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.
Highlights
At the 3rd day, the body weight of adriamycin group sharply declined, which revealed the high toxicity of this commercial doxorubicin hydrochloride injection. These results indicated that A54-Dex-PLGA/DOX/SPIO micelles could target to the tumor tissue more efficiently, reduced toxicity and had better anti-tumor effect compared with Dex-PLGA/DOX/SPIO micelles
A54 peptide modified and SPIO encapsulated had no significant effect on encapsulation efficiency, drug loading and in vitro release of doxorubicin
The A54-Dex-PLGA/DOX/SPIO micelles were effectively transported to the tumor tissue through the EPR effect, the targeting peptide A54 enhanced endocytosis of the micelles, could achieve diagnostic, monitoring and therapeutic purposes
Summary
These results indicated that A54-Dex-PLGA/DOX/SPIO micelles could target to the tumor tissue more efficiently, reduced toxicity and had better anti-tumor effect compared with Dex-PLGA/DOX/SPIO micelles. This is mainly because A54-Dex-PLGA/DOX/SPIO micelles successfully inherited the ability of Dex-PLGA graft to enter cells and the ability of biological molecules A54 peptides to target liver cancer cells BEL-7402, and transported drugs into the tumor cells through the EPR effect and targeting molecules mediated endocytosis to obtain a better therapeutic effect. The assay of in vitro and in vivo anti-tumor activities indicated that A54-Dex-PLGA/DOX/SPIO micelles could reduce the toxicity and revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles.
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