Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages.

Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed. Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.

Nuclear-targeting TAT-PEG-Asp8-doxorubicin polymeric nanoassembly to overcome drug-resistant colon cancer.

AIM: Drug efflux-associated multidrug resistance (MDR) is a main obstacle to effective cancer chemotherapy. Large molecule drugs are not the substrates of P-glycoprotein, and can circumvent drug efflux and be retained inside cells. In this article we report a polymer-drug conjugate nanoparticulate system that can overcome MDR based on size-related exclusion effect. METHODS: Doxorubicin was coupled with the triblock polymeric material cell-penetrating TAT-PEG-poly(aspartic acid). The amphiphilic macromolecules (termed TAT-PEG-Asp8-Dox) could self-assemble into nanoparticles (NPs) in water. The antitumor activity was evaluated in drug-resistant human colon cancer HCT8/ADR cells in vitro and in nude mice bearing HCT8/ADR tumor. RESULTS: The self-assembling TAT-PEG-Asp8-Dox NPs were approximately 150 nm with a narrow particle size distribution, which not only increased the cellular uptake efficiency, but also bypassed P-glycoprotein-mediated drug efflux and improved the intracellular drug retention, thus yielding an enhanced efficacy for killing drug-resistant HCT8/ADR colon cancer cells in vitro. Importantly, the TAT-PEG-Asp8-Dox NPs enhanced the intranuclear disposition of drugs for grater inhibition of DNA/RNA biosynthesis. In nude mice bearing xenografted HCT8/ADR colon cancers, intravenous or peritumoral injection of TAT-PEG-Asp8-Dox NPs for 22 d effectively inhibited tumor growth. CONCLUSION: TAT-PEG-Asp8-Dox NPs can increase cellular drug uptake and intranuclear drug delivery and retain effective drug accumulation inside the cells, thus exhibiting enhanced anticancer activity toward the drug-resistant human colon cancer HCT8/ADR cells.

[The ophthalmic applications of nanotechnology].

This paper briefly reviews the researches and applications of nanotechnology in ophthalmological field recent years. Nanotechnology is the production of modern science and advanced engineering. In ophthalmological field it is generally applied on foundational investigation, medicine carrying agent, biomaterial, diagnosis and therapy. It helps us observe and control physiological and pathological phenomenon at nanometer level precisely. As new drug carriers, drug-loaded nanoparticles have lots of advantages with its targeting options and sustained drug release. As biomaterial it also has better biocompatible. It is a promising material in clinical application. The diagnosis and treatment level would be improved definitely by nanotechnology.

[Effect of sintering temperature on mechanical properties of dental zirconia toughened alumina ceramics].

PURPOSE: To investigate the effect of sintering temperature on mechanical properties of dental zirconia toughened alumina (ZTA) ceramics prepared by gel-casting technique. METHODS: The samples prepared by gel-casting were sintered at 1100, 1200, 1250, 1300 and 1400degrees centigrade for each group. The flexural strength, fracture toughness, Vickers hardness and brittleness index were obtained and microscopic morphology of each group was observed under scanning electron microscope (SEM). The data were statistically analyzed using SPSS 19.0 software package. RESULTS: The flexural strength, fracture toughness and Vickers hardness increased with the increasing sintering temperature during 1100~1400degrees centigrade. The lowest brittleness index (0.74±0.16) µm-1/2 was observed in group sintered at 1200degrees centigrade and the highest (2.76±0.14) µm-1/2 was at 1400degrees centigrade (P<0.05), while the flexural strength of these two groups was (46.89±3.24) MPa and (349.64±54.72) MPa, respectively. CONCLUSIONS: The ZTA dental ceramics exhibit good machinability with proper sintering temperature (1200degrees centigrade) and the strength meets the requirement of clinical application.

[Comparison of the shear bond strength by using nano silica sol to zirconia basement and veneer porcelain].

PURPOSE: To investigate the feasibility of using sol gel technique to produce thin layer nano silicon dioxide on zirconia ceramic surface and the effect of improving shear bond strength between zirconia and veneer porcelain. METHODS: The presintered zirconia specimen was cut into a rectangle block piece (15 mm×10 mm×2.5 mm), a total of 40 pieces were obtained and divided into 4 groups, each group had 10 pieces. Four different treatments were used in each group respectively. Pieces in group A (control group) were only sintered at 1450°C to crystallization; pieces in group B underwent 30% nano silica sol infiltration first and then were sintered at 1450°C to crystallization; piece in group C underwent crystallization first at 1450°C, then 30% nano silica sol infiltration and were sintered at 1450°C again; pieces in group D was coated by nano silica sol and then sintered at 1450°C to crystallization; ten rectangle block pieces (12 mm×8 mm×2 mm) in group E were made. Cylinder veneers 5 mm in diameter and 4 mm in height were produced in each group and the shear bond strength was tested. Data were statistically analyzed by SPSS 19.0 software package. RESULTS: The shear bond strength of the 5 group specimens were: (28.12±2.95) MPa in group A, (31.09±3.94) MPa in group B, (25.60±2.45) MPa in group C, (31.75±4.90) MPa in group D, (28.67±3.95) MPa in group E, respectively. Significant differences existed between the 5 groups, and group C had significant difference compared with group B and D. CONCLUSIONS：① Use of nano silicon sol gel on presintered zirconia surface to make thin layer of nano silicon dioxide can improve the shear bond strength between zirconia and veneer; ②Using nano silicon sol gel on crystallization zirconia surface to make thin layer of nano silicon dioxide will decrease the shear bond strength between zirconia and veneer; ③ Zirconia veneer bilayer ceramic has the same shear bond strength with porcelain fused to Ni Cr alloy; ④Use of sol gel technique to produce thin layer nano silicon dioxide on zirconia ceramic surface is feasible and can improve shear bond strength between zirconia and veneer porcelain.

Preparation and application of porous nitrogen-doped graphene obtained by co-pyrolysis of lignosulfonate and graphene oxide.

Nitrogen-doped graphene with in-plane porous structure was fabricated by simple co-pyrolysis of lignosulfonate and graphene oxide in the presence of urea. Lignosulfonate first performs as a dispersant adsorbed on the surface of graphene oxide to prevent the aggregation of graphene oxide sheets for preparing homogeneous nitrogen-containing precursor, and then acts as a porogen to render graphene sheets with nanopores in the pyrolysis process of the nitrogen-containing precursor. Urea was used as a nitrogen source to incorporate nitrogen atoms into graphene basal plane. The special nanoporous structure combined with nitrogen content of 7.41at.% endows the nitrogen-doped graphene electrode material with super capacitance up to 170Fg(-1), high rate performance, and excellent cycling stability.

[Experimental study of osseointegration of nHA/BG coating and Bio-Oss in implant defects].

PURPOSE: To evaluate bone regeneration in defects at titanium implants with nHA/BG coating in conjunction with Bio-Oss. METHODS: Four mandibular premolars were extracted in 6 Beagle dogs. After 3 months, buccal dehiscence-type defects (2.25 mm×3 mm×4 mm) were surgically created following implant site. The three treatment modalities were randomly allocated: nHA/BG implant/Bio-Oss, nHA/BG implant/blood clot, and mHA implant/Bio-Oss. After 8 and 16 weeks, the dogs were sacrificed respectively. A histomorphometric analysis was performed. The data was analyzed with SPSS 13.0 software package for Student's t test and ANOVA. RESULTS: At 8- and 16-week, nHA/BG implant group revealed comparable mean BIC (30% to 18% versus 61% to 53%). However, mHA implant/Bio-Oss group revealed significantly lower mean BIC (21% versus 46%) values than nHA/BG implant/Bio-Oss group.A significant difference was observed for the mean BIC and RA values at 8-week between nHA/BG implant/Bio-Oss group and mHA implant/Bio-Oss group. CONCLUSIONS: It is concluded that the application of Bio-Oss graft did not seem to interfere with the nHA/BG coating activity, but ensured a stabilization of the newly formed bone for defects.