| Currently the main means for cancer treatment are surgery, radiotherapy, chemotherapy, biological therapy and so on. However, all of these therapeutics bring great suffering to patients and have no obvious effect on patients with advanced cancer. It is imperative to reasearch effective and low damage targeted antitumor treatment. Recently in the wake of nanotechnology combining with life and medical sciences, nanobiomedicine is becoming one of the new compelling interdisciplinary areas. Nanodiamonds as a representative of nanoparticles, has its special biocompatible, non-toxic, small size, optical and chemical stability and easy surface modification, whose potential applications in the biomedical field raise widespread concern.In the article, one is that we selected nanodiamond(ND) as a carrier and transferrin(Tf) as a targeted ligand to prepare targeted carrier. The other is that DOX chose as a drug model to prepare targeted drug delivery system. The main work is as follows:1.The FND-PL-Tf targeted nanoparticles were prepared by polylysine (PL) as a crosslink. Human cervical carcinoma cells (HeLa) as an in vitro model, laser scanning confocal microscopy and flow cytometry as detection means to study the interaction of FND-PL-Tf and cells, the results found that FND-PL-Tf nanoparticles could enter living cells and located in the cytoplasm; the cellular uptake of FND-PL-Tf was dependent on particle concentration, the nanoparticle surface conjugated transferrin and dosing time, through clathrin-dependent and transferrin receptor-mediated endocytosis. The interaction between FND-PL-Tf nanoparticles with conjugated different transferrin ligand density and HeLa cells was showed that the cellular uptake the least amount of FND-PL-Tf nanoparticles with maximum coupling Tf, which may be closely related to the steric effect. It implied that the uptake of FND-PL-Tf nanoparticles was related to surface transferrin density. The study displayed that FND-PL-Tf nanoparticles could target cancer detection.2. Firstly, different nanodrugs were prepared by optimizing conditions. Then the nanoparticles were treated with HepG2 cells to determine the best way of the preparation. The ND-Tf-DOX nanoparticles were produced via the formation of amide bond between the complex of Tf-DOX and the carboxylated ND. The amounts of Tf conjugated and the amount of DOX adsorbed was determined from the difference between the Tf/DOX concentration before and after the adsorption by analyzing the Tf/DOX solutions using a UV-Vis spectrophotometer at 280 nm or 480 nm, which were nearly (790±35) μg/mg and (70±7) μg/mg. The ND-Tf-DOX complexes possessed an average size of (235±1.8) nm and a Z potential of (-8.95±1.5) mV with dynamic laser light scattering measurement.3. HepG2, HeLa and HEK293 cells were selected as the in vitro cell models, the interaction between ND-Tf-DOX and cells had been discussed by meams of flow cytometry, laser scanning confocal microscope and MTT assay. The results showed that the ND-Tf-DOX nanomedicine entering cells was depended on the time, the energy, the temperature. The ND-Tf-DOX nanomedicine endocytosis into cells through the clathrin-dependent and transferrin receptors (TfR)-mediated and located within lysosomes. The uptake of ND-Tf-DOX nanomedicine was related to the amount of TfR expression on the surface of cells. MTT assay showed the excellent biocompatibility of ND and ND-Tf nanoparticles. Compared with the ND-DOX complex, the ND-Tf-DOX nanomedicine demonstrated more lethality to cells. These results indicated that the ND-Tf-DOX nanomedicine could be designed to targeted therapeutic drugs. |
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