Authors: Yang Ge, Ke Shuai Lu, Xue Yan Su
Abstract: These stable self-assembled nanoparticles were characterized by dynamic light scattering, transmission electron microscopy, and atomic force microscopy,which demonstrated that the nanosystem consists of spherical particles with a smooth surface both in aqueous environment and in dried state. Toxicity measurements showed that the composition is nontoxic when tested either on cell cultures or in animal feeding experiments. To evaluate the potential of the nanosystem for intracellular drug delivery and gene, the nanoparticles were fluorescently labeled and folic acid was attached as a cancer cell-specific targeting moiety. The quantitative data obtained by digital processing of the intensity of green color of each pixel in the pictures inside the cell boundaries and total intensity of fluorescence inside the cells showed thattargeted particles internalized into the cells significantly faster and the total accumulation of these particles was substantially higher in the cancer cells.
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Authors: Nur Shafawati binti Rosli, Azhar Abdul Rahman, Azlan Abdul Aziz
Abstract: Nanoscale particles of gold nowadays dominate a great deal of attention for biomedical applications. Better knowledge of the nano-bio interface will lead to advanced biomedical tools for diagnostic imaging and therapeutics. In this review, recent progress in the elucidating of how size and concentration of gold nanoparticles (AuNPs) affect cellular uptake will be discussed. Due to its small size, AuNPs can be administered conveniently via intravenous injection. The ability to enter cells is one of the factors that determine the clinical utility of nanoparti¬cles (NPs). The size of AuNPs is one of the limitations in the potential use of gold markers for medical imaging or tracking of harder tumors. Within the size range of 10-100 nm, AuNPs of diameter 50 nm demonstrate the highest uptake. Efficient accumulation of AuNPs into cells also can be achieved at higher concentration. The fewer AuNPs are in the solution, the lesser chance for a receptor to receive gold nanoparticle; “mem¬brane wrapping” time is longer, resulting to lower uptake by the cell. Theoretical models support the size- and concentration-dependent NP-uptake. Endocytosis is one of the major pathways for cellular uptake of NPs. NPs are internalized by cells through endocytosis process and trapped in endosomes, which is then fuse with lysosomes for processing before being transported to the cell periphery for excretion. Exocytosis of NPs is also dependent on the size and concentration of the NPs, however, the trend is different compared to endocytosis process. These findings provide useful information in the design and optimization of the NP-uptake at a single cell level for effective applications in imaging, diagnosis, therapeutics, and targeting.
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Authors: Gang Li, Dong Hai Lin, Xin Xin Xie, Li Fang Qin, Jun Teng Wang
Abstract: PLGA nanoparticles (PLGA-NPs) are being extensively studied as drug carriers for their controlled release, biodegradability and biocompatibility. This study evaluated the cellular uptake of PEGylated PLGA-NPs in Hela cells. MePEG-PLGA (5%-15%) was used to prepare PEG modified PLGA nanoparticles (PEG-PLGA-NPs), and the fluorescent marker DiI was encapsulated in the nanoparticles for the visualized analysis. The nanoparticles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by Hela cells. Results showed that PLGA nanoparticles were lowly cytotoxic and could be uptaken by Hela cells freely. PEG-PLGA-NPs had faster cellular uptake than that of nude PLGA nanoparticles, especially 10%PEG-PLGA-NPs. It suggested that the surface modification of PLGA-NPs by PEG notably improved the cellular uptake.
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Authors: A. Apirakaramwong, Perayot Pamonsinlapatham, S. Techaarpornkul, Praneet Opanasopit, Suwannee Panomsuk, S. Soksawatmaekhin
Abstract: Chitosan (CS) has a high potential for gene delivery into mammalian cells. However, its uptake mechanism is not well clarified. We investigated the effects of inhibitors of clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein), macropinocytosis (LY 29004 and wortmannin), microtubuli polymerization (nocodazole) and of membrane cholesterol recycle (methyl-β-cyclodextrin) on the transfection efficiency with CS/pEGFP complexes and on the internalization of CS/rhodamine-labeled pEGFP complexes by hepatoma cell line (Huh 7 cells). The transfection was blocked by nocodazole, genistein, and methyl-β-cyclodextrin, respectively. CS/DNA complexes internalization was clearly inhibited by genistein. We conclude that the complexes uptake predominantly by caveolin-mediated pathways. In addition, fluorescence colocalization studies with acidotropic probes, LysoSensor dye, illustrated that CS/DNA complexes are targeted to lysosomes for the degradation after internalization.
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Authors: Annegret Potthoff, Tobias Meissner, Volkmar Richter, Wibke Busch, Dana Kühnel, Susanne Bastian, Maria Iwe, Armin Springer
Abstract: The increasing use of nanoparticles makes it necessary to check up possible toxicological risks of this new materials class. In this paper we describe on two nanopowders (tungsten carbide, titanium nitride) which methods and parameters of a chemical-physical characterization are needed in forefront of toxicological experiments. This includes investigation on the powder itself as well as on particles suspended in water and physiological media, respectively. The most important result is that nanoparticles agglomerate in serum-free medium within minutes, whereas in the present of serum an agglomeration is inhibited. Hence, we have physiological suspensions with well-distributed stabilized particles which allow performing toxicological testing under reproducible conditions. Furthermore we could prove that tungsten carbide particles were taken up into cells, but no acute toxicity was found determined by means of in vitro viability tests with different cells.
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Abstract: We have attempted to realize new biomolecular-inorganic nanohybrids with two different functions, one from inorganic moiety and the other from biological one. Recently we were quite successful in demonstrating that a two-dimensional inorganic compound like layered double hydroxide (LDH) can be used as gene or drug delivery carriers. Such inorganic vectors are completely new and different from conventionally developed ones such as viral-based, naked, and cationic liposomes, those which are limited in certain cases of applications due to their toxicity,
immunogenecity, poor integration, and etc. But the mentioned problems can be overcome by synthesizing inorganic vectors properly with non-toxic metal ions having biological compatibility. Since LDHs with positive layer charge have an anion exchange capacity, functional biomolecules with a negative charge can be intercalated into hydroxide layers of LDH by a simple ion-exchange
reaction to form a bio-LDH nanohybrid. We also found that the hydroxide layers of LDHs could protect the intercalated molecules very efficiently. If necessary, inorganic materials, as reservoir and delivery carrier, can be intentionally removed by dissolving it in an acidic which offer a way of recovering the encapsulated biomolecules. The possible roles of inorganic lattice as the gene and
drug delivery carrier will be shown by demonstrating the cellular uptake experiments of FITC, fluorophore, with laser scanning confocal fluorescence microscopy. A
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