Abstract

BackgroundThe development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have anticancer properties, but doses at therapeutic levels have unacceptable side effects. Here we investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug.MethodsSynthesized TPGS-FA was characterized by FTIR, UV-visible and 1H NMR spectroscopy, and TPGS loaded with NC was evaluated for its ability to induce apoptosis in Huh7 cells by Annexin V/PI and MTT assays, and observed by laser scanning confocal microscopy and inverted phase contrast microscopy.ResultsTPGS-FA/NC complexes were prepared successfully, and were homogenious with a uniform size of ~ 14 nm diameter. NC was released from the TPGS-FA/NC complexes in a controlled and sustained manner under physiological conditions (pH 7.4). Furthermore, its cytotoxicity to hepatocarcinoma cells was greater than that of free NC.ConclusionsTPGS-FA is shown to be useful carrier for drugs such as NC, and TPGS-FA/NC could potentially be a potent and safe drug for the treatment of hepatocellular carcinoma.

Highlights

  • The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge

  • FITC Annexin V apoptosis Detection Kit was purchased from Thermofish Scientific(Thermofish, waltham, USA) MTT was purchased from Beijing Solarbio Science & Technology Co., Ltd.(Solarbio, Beijing, China)

  • The folic acid could be used as a targeting ligand, which could help TPGSFA/nitidine chloride (NC) conjugates enter Huh7 cells via the folate receptor-mediated endocytic pathway

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Summary

Introduction

The development of novel and effective drugs for targeted human hepatocellular carcinoma still remains a great challenge. The alkaloid nitidine chloride (NC), a component of a traditional Chinese medicine, has been shown to have anticancer properties, but doses at therapeutic levels have unacceptable side effects. We investigate folic acid modified D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-FA) as a potential carrier for controlled delivery of the drug. Novel drugs and effective drug delivery systems for liver cancer therapy need to be developed to overcome this chemoresistance [14]. TPGS has been shown to improve the bioavailability of certain anticancer drugs [18, 19], and has been reported have selective cytotoxic activity against cancer cells by inducing their apoptosis [20]. Optimizing the drug delivery system is a necessary procedure for enhancing the targeting of drugs to tumor cells/ tissues [21, 22]. The exact mechanism of the FR delivery system is still not fully understood, many folatemodified nano-micelles have been discovered with good therapeutic effects, because of receptormediated endocytosis [27, 30]

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