The Use of Solid Lipid Nanoparticles

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Introduction Proteins accumulate in the nucleus to signal the specific entry of molecules through nuclear pore complex (NPC) [1-3]. This mechanism was observed first in nucleoplasmin, an acidic protein that binds histones H2A and H2B during nucleosome assembly[4-8]. In vertebrates Nuclear pore complex weighs 125Mda in mass and contains 50-100 polypeptides. Thus, for macromolecules to cross the NPC, a signal mediated transport mechanism is required. Although several pathways exist for nuclear transport, classical nuclear localization signals (NLSs) that contain one or more clusters of basic amino acids are well known and characterized [9]. Nuclear localization signals (NLSs) are stretches of residues in proteins that facilitate the import of protein residues into the nucleus. Nuclear localization signal exists in the form of protein peptides bound to carrier proteins for trafficking nuclear proteins into the nucleus. Small molecules less than 40-45kda diffuse freely in and out of the nucleus through nuclear pore complexes between the cytoplasm and the nucleus using soluble carrier proteins [10]. However, the nuclear import of larger molecules, is an energy-dependent process mediated by specific targeting signals called as nuclear localizing sequences (NLSs).[10] These oligopeptides that are less than 10 AAs binds directly to a group of proteins called importins. The structural and functional domains of importin-α consists of a short basic N-terminal called as Importin-β binding domain (11-13) and a large NLS-binding domain of armadillo (Arm) repeats (14). Importin-α transports cargo proteins into the nucleus, and the importin-α is further recognized by importin-β to form a heterotrimer complex that interacts with the hydrop... ... middle of paper ... organs, respectively[52-60]. Trastuzumab conjugated with NLS and labeled with111In using diethylenetriaminepentaacetic acid (DTPA) for receptor-mediated internalisation of the drug by low-energy augur radioimmunotherapy showed increased internalization of 111Intrastuzumab (made of 6 NLS-peptides) in SK-BR-3, MDA-MB-361, and MDA-MB-231 cells from 7.2% ±0.9%, 1.3% ±6 0.1%, and 0.2% ± 0.05% to 14.4%± 6 1.8%, 6.3% ± 0.2%, and 0.9% ±0.2%, respectively [61]. The levels of HER2/neu expression in SK-BR-3, MDA-MB-361, and MDA-MB-231 human breast cancer cells were very high, intermediate and low, respectively [ 61]. Thus, by selectively exploiting the biological property of NLS peptides for enhancing the drug delivery to the target nucleus offers wide range of therapeutic options in chemotherapy, eliciting immunomodulatory effects, and radio immunotherapy.
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