Magnetic graphene oxide nanoflakes for dual RNA interfering delivery and gene knockdown in prostate and liver cancers.

The development of synthetic carriers for small interfering RNA (siRNA) and plasmids is crucial for effective gene therapy. In this study, we synthesized magnetic graphene oxide nanoflakes as carriers for siRNA delivery, with the goal of knockdown specific genes such as the green fluorescence protein (GFP). Our approach combined magnetically reduced graphene oxide with polyethylenimine (PEI) crosslinked to its surface using carbonyl diimidazole. To evaluate the adsorption capacity of the PEI-modified nanocomposite, we investigated its ability to bind two types of nucleic acids: short-hairpin (sh)RNA plasmids and siRNA targeting GFP. The nanocomposite exhibited significant adsorption, with maximum capacities of 426 ng/µg for shRNA and 71 ng/µg for siRNA, respectively. Simultaneous delivery of siRNA and shRNA using our designed nanocomposites was successfully achieved in human hepatoma and prostate cancer cells. Under magnetic guidance, the knockdown efficiencies reached 73.5 % in hepatoma cells for dual delivery of siRNA and shRNA. Our findings revealed that the nanocomplexes were internalized by the cells through a caveolae-dependent endocytosis mechanism. The demonstrated ability of the nanoflakes to efficiently transport siRNA and shRNA, with high loading capacity, controlled release, and magnetic targeting, resulted in effective GFP knockdown in vitro. These findings highlight the potential of magnetic graphene oxide nanoflakes as promising carriers for siRNA delivery and gene knockdown in therapeutic applications.

Traumatic Retinal Detachment in Patients with Self-Injurious Behavior: An International Multicenter Study.

PURPOSE: To describe the clinical characteristics, surgical outcomes, and management recommendations in patients with traumatic rhegmatogenous retinal detachment (RRD) resulting from self-injurious behavior (SIB). DESIGN: International, multicenter, retrospective, interventional case series. PARTICIPANTS: Patients with SIB from 23 centers with RRD in at least 1 eye. METHODS: Clinical histories, preoperative assessment, surgical details, postoperative management, behavioral intervention, and follow-up examination findings were reviewed. MAIN OUTCOME MEASURES: The rate of single-surgery anatomic success (SSAS) was the primary outcome. Other outcomes included new RRD in formerly attached eyes, final retinal reattachment, and final visual acuity. RESULTS: One hundred seven eyes with RRDs were included from 78 patients. Fifty-four percent of patients had bilateral RRD or phthisis bulbi in the fellow eye at final follow-up. The most common systemic diagnoses were autism spectrum disorder (35.9%) and trisomy 21 (21.8%) and the most common behavior was face hitting (74.4%). The average follow-up time was 3.3 ± 2.8 years, and surgical outcomes for operable eyes were restricted to patients with at least 3 months of follow-up (81 eyes). Primary initial surgeries were vitrectomy alone (33.3%), primary scleral buckle (SB; 26.9%), and vitrectomy with SB (39.7%), and 5 prophylactic SBs were placed. Twenty-three eyes (21.5%) with RRDs were inoperable. The SSAS was 23.1% without tamponade (37.2% if including silicone oil), and final reattachment was attained in 80% (36.3% without silicone oil tamponade). Funnel-configured RRD (P = 0.006) and the presence of grade C proliferative vitreoretinopathy (P = 0.002) correlated with re-detachment. The use of an SB predicted the final attachment rate during the initial surgery (P = 0.005) or at any surgery (P = 0.008. These associations held if restricting to 64 patients with ≥12 months followup. Anatomic reattachment correlated with better visual acuity (P < 0.001). CONCLUSIONS: RRD resulting from SIB poses therapeutic challenges because of limited patient cooperation, bilateral involvement, chronicity, and ongoing trauma in vulnerable and neglected patients. The surgical success rates were some of the lowest in the modern retinal detachment literature. The use of an SB may result in better outcomes, and visual function can be restored in some patients.

Efficacy and safety of biodegradable collagen-glycosaminoglycan polymer as a material for scleral buckling.

PURPOSE: To test the efficacy and safety of a biodegradable collagen-glycosaminoglycan (CG) polymer as the material for scleral buckling in rabbit eyes. METHODS: Segmental scleral buckling was performed by using a silicone sponge in one eye and a biodegradable CG polymer in the other eye of 20 rabbits. Wound and conjunctival reactions were evaluated by external photographs 1 day and then every week after surgery. Echography was used to evaluate the extent of the buckling effect. Electroretinograms were used to evaluate the retinal function after scleral buckling. Histology and immunohistochemistry were used to check the tissue reaction and distribution of myofibroblasts during wound healing. Scanning electronic microscopy of buckling materials was used to analyze structural changes after episcleral implantation. RESULTS: Biodegradable collagen initially achieved a buckling effect comparable to a silicone sponge; the buckling effect decreased after 1 month. Within 8 to 12 weeks, the collagen was gradually absorbed. After implantation, the collagen matrix degraded, and the pore size decreased as a result of compression and degradation. In contrast, no major structural changes were observed in silicone sponges, except some cell debris, fibrin, and blood cells were detected inside the porous structure of the sponge. The inflammatory responses were comparable between sponge and collagen in most areas of peribuckling histology. In areas of degraded collagen, a foreign body reaction was observable. Electroretinography revealed no detectable difference in retinal function between control and experimental eyes. CONCLUSIONS: Biodegradable collagen was used effectively and safely as a material for scleral buckling.

Photosensitizer in lipid nanoparticle: a nano-scaled approach to antibacterial function.

Photosensitization-based antimicrobial therapy (PAT) is an alternative therapy aimed at achieving bacterial inactivation. Researchers use various photosensitizers to achieve bacterial inactivation. However, the most widely used approach involves the use of photosensitizers dispersed in aqueous solution, which could limit the effectiveness of photodynamic inactivation. Therefore, the approaches to encapsulate the photosensitizer in appropriate vehicles can enhance the delivery of the photosensitizer. Herein, Toluidine Blue O (TBO) was the photosensitizer, and lipid nanoparticles were used for its encapsulation. The lipid nanoparticle-based delivery system has been tailor-made for decreasing the average size and viscosity and increasing the formulation stability as well as the wettability of skin. Usage of an appropriate vehicle will also increase the cellular uptake of the photosensitizer into the bacterial cells, leading to the damage on cell membrane and genomic DNA. Evidence of effectiveness of the developed PAT on planktonic bacteria and biofilms was examined by fluorescence microscopy and scanning electron microscopy. Lipid nanoparticles protected the photosensitizer from aggregation and made the application easy on the skin as indicated in data of size distribution and contact angle. The use of lipid nanoparticles for encapsulating TBO could enhance photosensitization-based antimicrobial therapy as compared to the aqueous media for delivering photosensitizers.

Treatment of retinal detachment resulting from posterior staphyloma-associated macular hole in highly myopic eyes.

PURPOSE: To evaluate the surgical outcome of retinal detachment resulting from a posterior staphyloma-associated macular hole in highly myopic eyes. METHODS: Fifty-seven consecutive highly myopic eyes with retinal detachment resulting from a posterior staphyloma-associated macular hole diagnosed between January 1993 and June 2003 were retrospectively studied. Anatomical reattachment of the retina and best-corrected visual acuity were measured. RESULTS: Six different operative methods were used to treat this condition with diverse retinal reattachment rates: long-acting gas tamponade only (12.5%); pars plana vitrectomy (PPV) with long-acting gas tamponade (42.8%); PPV with epiretinal membrane (ERM) peeling and long-acting gas tamponade (50.0%); encircling scleral buckling combined with PPV and long-acting gas tamponade (57.1%); encircling scleral buckling combined with PPV, ERM peeling, and long-acting gas tamponade (40.0%); and encircling scleral buckling combined with PPV and silicone oil tamponade (75.0%). Overall, successful retinal reattachment was achieved in 25 (43.9%) of 57 eyes after the first surgery. However, the ultimate success rate of retinal reattachment was 77.2% (44 of 57 eyes) after subsequent surgery. The mean preoperative visual acuity +/- SEM (in logarithm of the minimal angle of resolution units) was 2.08 +/- 0.55, and the mean postoperative visual acuity +/- SEM was significantly increased to 1.87 +/- 0.54 at the last follow-up (P = 0.038). The major cause of recurrent retinal detachment in the long-acting gas tamponade group was nonclosure of the macular hole. For vitrectomized eyes, the major cause was reopening of the macular hole, even with ERM formation and proliferative vitreoretinopathy. There was no obvious correlation between the extent of the detachment or lens status and the reattachment rate. CONCLUSIONS: The major causes of recurrent retinal detachment in the long-acting gas tamponade and vitrectomized groups were nonclosure of the macular hole and reopening of the macular hole, respectively. Furthermore, a lesser extent of retinal detachment was not associated with a higher anatomical success rate. More aggressive treatment such as silicone oil tamponade may need to be performed to overcome reduced natural adhesion due to posterior staphyloma with marked chorioretinal atrophy. Failure to initiate aggressive treatment can result in an unsatisfactory outcome and repeated surgery.