These factors all contributed to a reduction in MDR and were directed by the level of endosomal-mediated cellular uptake properties of such nanoparticles [100]. In chronic myelogenous leukaemia (CML), a Bcr-Abl positive status induces MDR properties through multiple pathways, including resistance to p53 and Fas ligand-induced apoptotic pathways [101]. The delivery system devised by Singh et al. [101] consisted of magnetic nanoparticles combined Inhibitors,research,lifescience,medical with paclitaxel

and was consequently administered to Bcr-Abl positive K562 leukaemic cell lines [101]. The addition of lectin functional groups to the nanoparticle complex served to aid cellular uptake by the target K562 cell line and also demonstrated a reduction in the IC(50) for paclitaxel within this cell line model [101]. Multiple myeloma is an additional tumour model

that has seen benefit from the exploitation of nanoparticle technology in its therapeutic Inhibitors,research,lifescience,medical avenues [76]. The study by Kiziltepe et al. [76] succeeded in developing a micelle-based nanoparticle delivery system containing doxorubicin and very late antigen-4 (VLA-4) antagonist peptides [76]. This delivery method not only accomplished enhanced cytotoxic activity when compared to doxorubicin alone, but also the addition of VLA-4 antagonist peptides served well in COX signaling inhibitors circumventing the phenomenon of cell-adhesion-mediated Inhibitors,research,lifescience,medical drug resistance due to the resultant impaired VLA-4 mediated adhesion of multiple myeloma cells to the stroma of bone marrow within CB.17 SCID murine multiple myeloma xenograft models [76]. Additionally, drug accumulation within the stroma of the multiple myeloma murine

xenograft models was also Inhibitors,research,lifescience,medical tenfold higher than the control murine model [76]. Yet another tumour model that has been investigated for the application of nanoparticle-based chemotherapy, for the purpose of avoidance of chemoresistance, is prostate cancer Inhibitors,research,lifescience,medical [102]. Gold nanoparticles are an attractive avenue for drug delivery researchers primarily due to their lack of complexity in their synthesis, characterization, and surface functionality [78]. Gold nanoparticles also have shape/size-dependent Molecular Cell optoelectronic characteristics [78]. The endosomal-based route for gold nanoparticle cellular uptake can be viewed as the primary advantage for circumventing MDR within the tumour cell, since the drug efflux pump is bypassed and the nanoparticle-held chemotherapeutic agent is released within the acidic environment of the endosome and allowed to penetrate the tumour cell cytoplasm [79]. Consequently, tumour progression phenotypes such as cell proliferation and level of apoptosis are affected to direct an amelioration of patient prognosis. Gold nanoparticle/antiandrogen conjugates were developed by Dreaden et al. [102], with the capacity to selectively bind to two surface receptors which are upregulated in prostate tumour cell surface.