Wang et al. have discussed these processes in detail [ 3••]. Here we summarise recent advances in both passive and active delivery of platinum-based anticancer complexes. Utilizing nanotechnology
to improve drug delivery is a well-known concept, however innovative designs of nano-vectors to achieve efficient drug delivery and their complexity are emerging [4•]. Carbon nanotubes (CNTs) are the most studied. Pristine CNTs are insoluble in most solvents and bear structural resemblance to carcinogenic asbestos fibres. However, coating CNTs with linear and/or branched poly(ethylene glycol) (PEG) units (1 and 2, Figure 1a) renders them more hydrophilic and more suitable for biomedical applications [5]. The toxic nature of pristine (non-functionalised) multi-walled and single-walled CNTs and ability to induce mesothelioma have been demonstrated. Bianco et al. have shown that mono-functionalisation, see more bi-functionalisation, and tri-functionalisation of CNTs (3–5, Figure 1b) give enhanced biocompatibility click here and can be translocated directly into the cytoplasm of cells. Non-biodegradable CNTs have the potential to accumulate in various tissues and organs [ 6], however the oxidative enzyme horseradish peroxidase (HRP) can catalytically degrade f-CNTs [ 7]. Tripisciano et al. have encapsulated CDDP into functionalised single-walled carbon nanotubes (SWCNTs). CDDP-SWCNTs are more cytotoxic than free CDDP towards
PC3 cancer cells, but less potent than CDDP towards DU145 cells [ 8]. Recently, Li et al. capped multi-walled carbon nanotubes (MWCNTs) with functionalized 1-octadecanethiol (ODT) gold nanoparticles (f-GNPs) to facilitate the effective delivery of CDDP (6). The presence
of the f-GNP at the tip of the MWCNTs hinders the encapsulated CDDP from leaving the narrow passage of the MWCNTs. The in vivo activity of CDDP in capped CDDP-MWCNTs towards MCF-7 breast cancer cells was enhanced (IC50 7.7 μM), compared to uncapped CDDP-MWCNTs (IC50 11.7 μM). These results suggest that f-GNP MWCNTs may be effective drug depots [ 9]. Reducing the size of the CNTs renders them more likely to pass into the cell, as seen for SWCNTs of 1–2 nm diameter. Guven et al. have synthesised ultra-short Progesterone carbon nanotubes (USCNTs) of ca. 1.4 nm diameter in which CDDP was encapsulated (7) and then wrapped with a surfactant. The CDDP-USCNTs were more potent than free CDDP in two breast cancer cell lines (MCF7 and MDA-MB-231) after 24 hours. Wrapping of USCNTs with a surfactant retards release of CDDP resulting in its higher cytotoxicity. For in vivo use, the surfactant molecules could be replaced with a cancer-specific protein [ 10]. Li et al. have entrapped a hydrophobic PtIV complex (8) within the inner cavity of MWCNTs. Chemical reduction converted the PtIV prodrug to its hydrophilic and cytotoxic PtII form triggering its release from the MWCNTs.