Abstract
A main hurdle for the success of tumor-specific liposomes is their inability to penetrate tumors efficiently. In this study, we incorporated a cell-penetrating peptide BR2 onto the surface of a liposome loaded with the anticancer drug cantharidin (CTD) to create a system targeting hepatocellular carcinoma (HCC) cells more efficiently and effectively. The in vitro cytotoxicity assay comparing the loaded liposomes’ effects on hepatocellular cancer HepG2 and the control Miha cells showed that CTD-loaded liposomes had a stronger anticancer effect after BR2 modification. The cellular uptake results of HepG2 and Miha cells further confirmed the superior ability of BR2-modified liposomes to penetrate cancer cells. The colocalization study revealed that BR2-modified liposomes could enter tumor cells and subsequently release drugs. A higher efficiency of delivery by BR2 liposomes as compared to unmodified liposomes was evident by evaluation of the HepG2 tumor spheroids penetration and inhibition. The biodistribution studies and anticancer efficacy results in vivo showed the significant accumulation of BR2-modified liposomes into tumor sites and an enhanced tumor inhibition. In conclusion, BR2-modified liposomes improve the anticancer potency of drugs for HCC.
Highlights
Hepatocellular carcinoma (HCC) is difficult to treat clinically; effective targeted drug delivery systems are needed (Zhang et al, 2016c)
Though liposomal delivery systems have been used with certain modification in a few clinical trials (Pattni et al, 2015), classical liposomes have been of little or no value as a carrier for anticancer drugs due to lack of specificity for given cancer cells and/or failure to penetrate tumor tissue (Liang et al, 2015)
It could be due to the ability of the BR2 peptide to bind to gangliosides, which were increasingly expressed in the tumor tissues as compared to normal tissues (Marquina et al, 1996; Ye et al, 1990)
Summary
Hepatocellular carcinoma (HCC) is difficult to treat clinically; effective targeted drug delivery systems are needed (Zhang et al, 2016c). Though liposomal delivery systems have been used with certain modification in a few clinical trials (Pattni et al, 2015), classical liposomes have been of little or no value as a carrier for anticancer drugs due to lack of specificity for given cancer cells and/or failure to penetrate tumor tissue (Liang et al, 2015). CPPs are able to accelerate the absorption of macromolecules via physiological mechanisms such as energy-dependent endocytosis and energy-independent direct penetration (Zhang et al, 2016a). Despite these advantages, CPPs are not widely used due to lack of tissue-selectivity (Deshayes et al, 2005). If a way to deliver CPPs to tumor tissue could be developed, it would greatly enhance their anticancer efficacy
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