In contrast, for A549 lung cancer cells (FR −ve), the uptake was independent

on the sequence of loading. The FR-nanogel-CDDP displayed superior antitumour activity towards A2780 xenografts in contrast to free CDDP [ 24]. The intracellular delivery of carboplatin has been investigated by coupling i.p. Wnt cancer administration with a folate-receptor-targeted liposomal system. The cytotoxicity is enhanced (twofold) in comparison to carboplatin itself towards human ovarian IGROV-I (FR +ve) cancer cells. Mice bearing the i.p.-grown human IGROV-1 ovarian tumour xenografts treated with FRT-carboplatin liposomes had an 83% survival rate [25]. EGF is another potential targeting ligand due to the overexpression of the EGF receptor in human tumours, in particular NSCLC non-small cell lung cancer. Bhirde et al. have attached cisplatin (dissolved in DMSO) and EGF to oxidised SWCNTs to target squamous cancer. In vivo studies revealed SWCNT–CDDP–EGF (19) were selective towards HNSCC head and neck squamous cell carcinoma. Tumour growth regression was significant in mice treated with SWCNT–CDDP–EGF bearing HNSCC xenografts in contrast to mice treated with SWCNT–CDDP [ 26•]. Biotinylated BMS-754807 in vitro epidermal growth factor (bEGF)

conjugated to a Pt(NH3)22+-gelatin nanocomplex (GP-Pt-bEGF, 20) gives rise to a twofold higher Pt concentration in A549 human adenocarcinoma (EGF +ve) compared to HFL1 lung fibroblasts (EGF −ve). Immunodeficient mice injected with an A549 cell suspension treated with GP-Pt-bEGF nanoparticles displayed a reduction in tumour volume compared to mice treated with free CDDP which the tumour volume grew rapidly [ 27••]. The high molecular weight of full length EGFR monoclonal antibody if used as a targeting ligand may hinder its penetration into tumour cells; furthermore interaction with the Fc receptor on normal tissues may disturb its specific targeting. Therefore, single-chain antibodies against the EGFR (ScFvEGFR) lacking the Fc receptor have been conjugated onto the surface of ScFvEGFR-heparin-CDDP nanoparticles

(with Pt(NH3)22+ bound to carboxylates, 21). Nanoparticle Adenosine conjugate 21 was most potent towards H292 (EGF +ve) human lung cancer cells with an IC50 of 1.1 μm. Kidneys from mice treated with 21 showed no change in either blood urea nitrogen (BUN) or creatine (CRE) levels, in contrast to CDDP which gave significant changes consistent with impaired renal function [28••]. Xu et al. have coupled a Pt(NH3)2-herceptin (L2, Figure 2g) dicarboxylato binding ligand onto dumbbell-like Au-Fe3O4 nanoparticles (22) to act as nanocarriers to deliver the platinum pharamacophore into SK-Br3 breast cancer (HER2 +ve) cells. Without the targeting agent, the platin-Au-Fe3O4-NPs were still active, but less than CDDP. Thus, herceptin enhances Pt uptake in SK-Br3 cells giving greater cytotoxicity owing to the specific targeting.