48 Transferrin-modified self-assembled HSA (human serum albumin) nanoparticles enhance drug delivery to tumors

Abstract

Objectives Taxanes like paclitaxel (Tax), docetaxel and cabazitaxel are effective chemotherapeutic drugs which have been used in various types of cancer in recent years. Taxanes are highly lipophilic and practically insoluble in water. In addition, their clinical applications are limited by their toxicity to normal tissues. Human serum albumin (HSA) nanoparticles (HSA-Nps) have been shown to be a promising drug delivery system. They act by enhancing the drug’s bioavailability in tumors via SPARC. To further improve the targeting efficiency of HSA-Nps, transferrin (Tf) was covalently coupled to the HSA-Nps using NHS-PEG2000-MAL as a bifunctional cross-linking agent, since transferrin receptor is highly expressed in most tumor cells. Methods HSA-Nps encapsulating paclitaxel (HSA-Nps-Tax) were obtained using the salting-out method. The cross-linking agent was then added to react with the amino groups of HSA-Nps. Meanwhile, sulfhydryl groups were introduced to Tf by 2-iminothiolane, which reacts with the amino groups of transferrin. In the third step, sulfhydryl-reactive transferrin was covalently coupled to the HSA-Nps. Results Tf-modified HSA-Nps-Tax (Tf-HSA-Nps-Tax) had an excellent mean particle size (180 nm) and stability, and had greater cytotoxicity and apoptosis-inducing activity in MCF-7 cells than HSA-Nps-Tax in vitro. Furthermore, Tf-HSA-Nps-Tax showed greater tumor growth inhibition than HSA-Nps-Tax in vivo, which highlighted the advantage of transferrin targeting of tumor cells. Conclusions Tf-modified self-assembled HSA Nps are promising targeted carriers for tumor therapeutics. Acknowledgments This research was financially supported by Jilin Province Science and Technology Development Program (Grant Nos. 20140311072YY and 20150520141JH).