Abstract
Background and Aims: Currently there is no appropriate method for effective and targeted delivery of chemotherapeutic agents to tumor sites. The conventional chemotherapy is afflicted with lack of effective drug delivery to the tumor site, unwanted injury to actively dividing healthy cells, and numerous side effects due to toxicity. The present study was aimed to develop a biologically derived nanoparticle based drug delivery system for the effective treatment of primary hepatic tumors.
Methods: Intrahepatic tumors were induced in immunosuppressed mice using PLC/PRF/5 hepatocellular carcinoma (HCC) cells stably transfected with a mammalian expression vector carrying luciferase gene for in-vivo imaging. Nanovesicles ranging from 80-150 nm were isolated from bovine skim milk using ultracentrifugation and characterized using nanoparticle tracking analysis (NTA) and electron microscopy. Purified nanovesicles were loaded with chemotherapeutic agents and antisense oligonucleotides for grossly deregulated microRNAs specific to HCC. Animals with uniform intrahepatic tumors were injected with nanovesicle loaded anticancer agents through tail vein. Tumor regression was monitored weekly using in-vivo imaging system and the animals were maintained up to 8 weeks.
Results: Bioluminescence based in-vivo imaging demonstrated significant reduction of tumor size in treated animals compared to untreated controls. There was increased survival rate and complete absence of metastasis in all treated animals. Untreated mice developed large intrahepatic tumors, which also metastasized to other organs. There were no side effects or immunological reactions in animals injected with plain nanovesicles without loading of any anticancer agents.
Conclusions: The present study demonstrated that milk derived nanovesicles can be effectively used for successful delivery of anticancer agents into intrahepatic tumors. Nanovesicle based targeted drug delivery system could be an effecient method for the treatment of primary hepatic tumors.* Presenting author E-mail: [email protected]
Note: This abstract was not presented at the meeting.
Citation Format: Joseph George, Nobuhiko Hayashi, Takashi Saito, Mikihiro Tsutsumi, Mutsumi Tsuchishima. Targeted delivery of chemotherapeutic agents employing nanovesicles effectively reduced intrahepatic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2178.
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