Preliminary study on transdermal characteristics and sunface anesthetic effects of lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome in animals / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To prepare a new dental topical anesthetics, lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome (LID-TAT-N), and to evaluate its transdermal properties and topical anesthesia effects.</p><p><b>METHODS</b>LID-TAT-N was prepared using reverse-phase evaporation method, and lidocaine loaded conventional liposome (LID-CL) was prepared in the same manner as positive control. The diameter, ζ potential and encapsulation efficiency of LID-TAT-N and LID-CL were measured. The skin permeation of LID-TAT-N was examined, and compared with LID-CL and lidocaine injection (LID-IJ, as negative control), using a Franz diffusion cell mounted with depilated mouse skin in vitro for 12 hours. Each experiment was repeated six times. The anesthetic effect of the new topical anesthetic was investigated on the cornea of rabbits.</p><p><b>RESULTS</b>The mean diameter of LID-TAT-N was smaller than that of LID-CL [(152.7 ± 10.6) nm vs. (259.5 ± 15.5) nm, P < 0.01]. The 12 h cumulative permeation amount was significantly higher in LID-TAT-N group [(1 340.0 ± 97.5) µg · cm(-2)] than those of LID-CL and LID-IJ groups [(1 060.6 ± 80.2), (282.6 ± 65.1) µg · cm(-2), respectively, P < 0.05]. Rabbit corneal reflex results showed that LID-TAT-N had anesthetic effect and the duration of analgesia [(24.8 ± 2.8) min] was also longer than that of LID-IJ [(14.5 ± 2.3) min, P < 0.05].</p><p><b>CONCLUSIONS</b>LID-TAT-N had good transdermal ability, and the advanced skin penetration feature can improve its tropical anesthetic effect.</p>

Trastuzumab-Conjugated Liposome-Coated Fluorescent Magnetic Nanoparticles to Target Breast Cancer

OBJECTIVE: To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. MATERIALS AND METHODS: The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin(R))-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. RESULTS: We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging. CONCLUSION: Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.

Comparison of the targeting properties of 2-deoxy-D-glucose-conjugated nanoparticles to breast cancer MDA-MB-231 cells and breast fibroblasts cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To compare the differences in uptake of 2-deoxy-D-glucose (2-DG)-conjugated nanoparticles between breast carcinoma MDA-MB-231 cells with high metabolism and breast fibroblasts with normal metabolism, and investigate the feasibility of using the coated nanoparticles as a MRI-targeted contrast agent for highly metabolic carcinoma cells.</p><p><b>METHODS</b>The γ-Fe2O3@DMSA-DG was prepared. The glucose metabolism level of both cell lines was determined. The targeting efficacy of γ-Fe2O3@DMSA-DG and γ-Fe2O3@DMSA NPs to breast carcinoma MDA-MB-231 cells and breast fibroblasts at 10 min, 30 min, 1 h and 2 h was measured with Prussian blue staining and UV colorimetric assay. MRI was performed to visualize the changes of T2WI signal intensity.</p><p><b>RESULTS</b>Prussian blue staining showed more intracellular blue granules in the MDA-MB-231 cells of γ-Fe2O3@DMSA-DG NPs group than that in the γ-Fe2O3@DMSA NPs group, and the γ-Fe2O3@DMSA-DG uptake was greatly competed by free D-glucose. As revealed by UV colorimetric assay, MDA-MB-231 cells also showed that the cellular iron amount of γ-Fe2O3@DMSA-DG group was significantly higher than that of the γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG + D-glucose group, statistically with a significant difference between them. MRI showed that the signal intensity of γ-Fe2O3@DMSA-DG group was decrease significantly, the T2 signal intensity was decreased by 10.5%, 37.5%, 72.9%, 92.0% for 10 min, 30 min, 1 h and 2 h, respectively. In contrast, the signal intensity did not show obvious decrease in the γ-Fe2O3@DMSA-DG group, the T2 signal intensity was decreased by 8.5%, 11.4%, 32.0%, 76.7% for 10 min, 30 min, 1 h and 2 h, respectively. However, HUM-CELL-0056 cells did not produce apparent difference for positive staining in the γ-Fe2O3@DMSA-DG group, γ-Fe2O3@DMSA group and γ-Fe2O3@DMSA-DG+D-glucose group, and the signal intensity also did not produce apparent difference.</p><p><b>CONCLUSIONS</b>γ-Fe2O3@DMSA-DG has good targeting ability to highly metabolic breast carcinoma (MDA-MB-231) cells. It is feasible to serve as a specific MRI-targeted contrast agent for highly metabolic carcinoma cells, and deserves further studies in vivo.</p>

Assemble of magnetic nanoparticles into the structure of cisplatin liposome / 药学学报

Effects of different procedures of magnetic nanoparticles into the liposome structure on the distribution of magnetic particles in the liposome were investigated. Magnetic liposomes with high-encapsulating rate of cisplatin (CDDP) were obtained. Fe3O4 magnetic nanoparticles which was modified by organic functional group on surface was synthesized by an one-step modified hydrothermal method. The CDDP magnetic liposomes were prepared by a film scattering-ultrasonic technique and the concentrations of CDDP in the liposomes were measured by graphite furnace atomic absorbance spectroscopy. Magnetic liposomes with different microstructure were prepared by the two different procedures, where the magnetic particles were combined with phospholipid before the film preparation to form liposome in procedure I, and drug solution and the magnetic particles were mixed before hydrating the lipids film to form liposome in procedure II. The liposome structure was observed by transmission electron microscope (TEM). The CDDP magnetic liposomes were prepared by the optimized method which was selected by orthogonal test. Encapsulation rate of the magnetic particles distributed in the phospholipid bilayer through the procedure I was 34.90%. While liposome, produced by the procedure II technique, contained magnetic particles in the interior aqueous compartment, which encapsulation rate was 28.34%. Encapsulation rates of both I and II were higher than that of conventional liposome. The release profile of all the three different liposomes in vitro fitted with a first-order equation. Because of distribution of magnetic particles in the phospholipid bilayer, the skeleton of phospholipid bilayer was changed. The releasing tl/2 of magnetic liposomes produced by the procedure I technique is 9 h, which is shorter than that of the other two liposomes. Assemble of magnetic nanoparticles into the structure of liposome was succeeded by the procedure I, which showed superiority than by procedure II whatever in CDDP liposome encapsulation efficiency and content of the magnetic particles and would ensure sustained-release character.

Application and advancement of magnetic iron-oxide nanoparticles in tumor-targeted therapy / 癌症

Recently, nanometer-sized magnetic particles have been intensively concerned and investigated due to their particularly large surface-to-volume ratio, quantum-size effect, magnetic character as well as their potential application in the area of bioscience and medicine. The most promising nanoparticles are magnetic iron oxide nanoparticles with appropriate surface modification, which have been widely used experimentally for numerous in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, drug delivery, hyperthermia and cell separation. To focus on one of the most important and fascinating subjects in nanobiotechnology, this review describes the current situation and development of magnetic iron oxide nanoparticles and their applications in drug delivery and hyperthermia in tumor-targeted therapy. The possible perspectives and some challenges to further development of these nanoparticles are also analyzed and discussed.