Studies On Nanobiotechnology-enabled Anti-tumor Drug Delivery And Inhibition Of Tumor Drug Delivery And Inhibition Of Tumor Cell Growth

Biotechnology, information technology and nanotechnology have been regarded as the three most important technologies in the 21st century. Nanomaterials refer to the materials which are at least in one dimension within the scale of 1-100 nm.In this investigation, we have designed and synthesized an amphiphilic co-polymer with hyper-branched poly (amine-ester) and polylactide (HPAE-co-PLA) to generate nanoparticles (NPs). These have been used to encapsulate a highly active hydrophobic anti-tumor agent,2-benzoylpyridine 4-ethyl-3-thio-semicarbazone (Bp4eT). Encapsulation in NPs was done in an effort to increase the anti-tumor activity of, this agent by facilitating its delivery to tumor cells. We have also examined and optimized the formulation parameters of the NPs that alter their drug-loading capacity and their physical, chemical and biological properties. The resulting NPs exhibited high Bp4eT-loading capacity and substantial stability in aqueous solution. In vitro drug release studies demonstrated a controlled drug release profile with increased release at acidic pH. Anti-tumor proliferation assays showed that both free drug and drug-encapsulated NPs markedly inhibited tumor cell proliferation in a time- and concentration-dependent manner. Direct microscopic observation revealed that the fluorescent NPs were taken up by cells and localized, in part, in organelles consistent with lysosomes. These results demonstrate a feasible application of the amphiphilic hyper-branched co-polymer, HPAE-co-PLA, as nanocarriers for intracellular delivery of potent anti-tumor agents.Paclitaxel (PTx)-loaded copolymer nanoparticles (NPs) have been previously described as more effective way for cancer therapy then free the chemical both in vitro and in vivo. The aim of this study was to test the hypothesis that our hydroxypropyl-β-cyclodextrin-based nanoparticles grafted with the RGD peptide would target the tumor cells with high expression of RGD receptor and would further enhance the anti-tumor efficacy of PTx. To employ the high binding affinity of a cyclic RGD peptide (cRGD), c(Arg-Gly-Asp-D-Phe-Cys) as an ayP3 integrin ligand to the surface of PTx-loaded p-maleimidophenyl isocyanate-hydroxypropyl-β-cyclodextrin (PMPI-HP-β-CD)-polylactide (PLA)-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) NPs (PMPI-HP-β-CD-PLA-DPPE-PTx). We observed in vitro that RGD-grafted NPs were more associated with B16 melanoma cells by binding toαγβ3 integrin than the cells without expression of RGD receptors. Hence, the active targeting strategy used in the current study is promising for enhanced anti-cancer drug delivery to the tumors expressing RGD-receptors.