EGFR-Targeted and NIR-Triggered Lipid-Polymer Hybrid Nanoparticles for Chemo-Photothermal Colorectal Tumor Therapy.

Background: Epidermal growth factor receptor (EGFR) is a major target for the treatment of colorectal cancer. Thus, anti-EGFR antibody conjugated lipid-polymer hybrid nanoparticles can offer a potential means of enhancing the efficacy of chemotherapeutics in EGFR overexpressing cancers. In addition, the combination of chemotherapy and photothermal therapy is a promising strategy for cancer treatment. Hence, it is highly desirable to develop a safe and effective delivery system for colorectal tumor therapy. Methods: In this study, EGFR-targeted and NIR-triggered lipid-polymer hybrid nanoparticles (abbreviated as Cet-Iri-NPs) were prepared with copolymer PPG-PEG, lipids DSPE-PEG-Mal and lecithin as carriers, CPT-11 as an anticancer chemotherapeutic agent, indocyanine green (ICG) as a photothermal agent, and cetuximab as a surface-targeting ligand. Results: In vitro analyses revealed that Cet-Iri-NPs were spherical with size of 99.88 nm, charge of 29.17 mV, drug entrapment efficiency of 51.72%, and antibody conjugation efficiency of 41.70%. Meanwhile, Cet-Iri-NPs exhibited a remarkable photothermal effect, and pH/NIR-triggered faster release of CPT-11 with near infrared (NIR) laser irradiation, which induced enhanced cytotoxicity against SW480 cells. Furthermore, the promoted tumor-growth suppression effect of Cet-Iri-NPs on SW480 tumor xenograft nude mice was achieved under NIR laser irradiation. Conclusion: These results indicate that the well-defined Cet-Iri-NPs are a promising platform for targeted colorectal cancer treatment with chemo-photothermal therapy.

Advanced platelet-rich fibrin (A-PRF) has an impact on the initial healing of gingival regeneration after tooth extraction.

OBJECTIVES: Platelet-rich fibrin (PRF) is widely used in wound healing because it contains several growth factors, including vascular endothelial growth factor (VEGF). In this study, we investigated the effects of advanced PRF (A-PRF) in early-stage gingival regeneration after tooth extraction. METHODS: Blood sample was collected from females beagle dogs (age: 12 months) before tooth extraction for A-PRF preparation. All animals were sacrificed by perfusion-fixation on postoperative days 1, 3, and 7. The upper jaws were prepared for hematoxylin and eosin staining and immunostaining (for CD34 and VEGF). The lower jaw samples were prepared for scanning electron microscope observations. Blood flow in the gingiva before and after surgery was measured using laser Doppler flowmetry. RESULTS: In the A-PRF group, a large number of microvessels were observed in the gingival tissue on postoperative day 1. The microvessels in the control group were fewer and sparse. Regarding the vascular resin cast, a large number of new blood vessels were observed on postoperative day 1 in the A-PRF group. A stronger CD34-positive signal was obtained around the blood vessels in the A-PRF group than in the control group. Further, a strong VEGF-positive signal was observed in the perivascular tissue in the A-PRF group. Gingival blood flow was significantly higher in the A-PRF group after surgery. CONCLUSION: A-PRF had a positive impact on angiogenesis in the gingiva through the induction of VEGF expression. Thus, A-PRF may be beneficial for gingival tissue regeneration.

Application of deproteinized bovine bone mineral as proangiogenic scaffold for alveolar bone formation in beagle dogs.

Alveolar bone repair after tooth extraction is essential after oral surgeries. Various grafting materials are used to promote the regeneration of lost alveolar bone. This study analysed the morphological features of the tissue regeneration process using deproteinized bovine bone mineral (DBBM). DBBM was used to densely fill the extraction sockets in beagle dogs. Following resin casting of the vasculature, stereomicroscopy and scanning electron microscopy were used to observe blood vessels and hard tissues in haematoxylin and eosin-stained sections on postoperative days 14, 30 and 90 in conjunction with vascular endothelial growth factor (VEGF) immunostaining to evaluate alveolar bone vascularization. On day 14 post-operation, the DBBM granules tightly filled the extraction sockets, maintained alveolar margin height and formed a scaffold for aiding angiogenesis and new bone formation. On day 30, new bone formation was observed around the DBBM granules. By day 90, bone tissue regeneration progressed in both groups but was more pronounced in the DBBM group. Alveolar margin height was maintained in the DBBM group throughout the study. Furthermore, VEGF expression in the DBBM group was detected around newly formed bone. We conclude that DBBM acts as a suitable scaffold for new bone generation, as well as angiogenesis around healing alveolar bone, and that it has the potential to play a key role in vascularization and bone formation.

Efficacy and safety of a parylene-coated occluder for atrial septal defect: a prospective, multi-center, randomized controlled clinical trial.

BACKGROUND: Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD). METHODS: One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran-Mantel-Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups. RESULTS: At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [-4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P < 0.05 vs. baseline). In the trial group, there was no significant difference in the serum nickel level before vs. after device implantation (P > 0.05). CONCLUSIONS: The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.