Upconverting Carbon Nanodots from Ethylenediaminetetraacetic Acid (EDTA) as Near-Infrared Activated Phototheranostic Agents.

This work describes the synthesis of nitrogen-doped carbon nanodots (CNDs) synthesized from ethylenediaminetetraacetic acid (EDTA) as a precursor and their application as luminescent agents with a dual-mode theranostic role as near-infrared (NIR) triggered imaging and photodynamic therapy agents. Interestingly, these fluorescent CNDs are more rapidly and selectively internalized by tumor cells and exhibit very limited cytotoxicity until remotely activated with a NIR illumination source. These CNDs are excellent candidates for phototheranostic purposes, for example, simultaneous imaging and therapy can be carried out on cancer cells by using their luminescent properties and the in situ generation of reactive oxidative species (ROS) upon excitation in the NIR range. In the presence of CNDs, NIR remote activation induces the in vitro killing of U251MG cells. Through the use of flow imaging cytometry, we have been able to successfully map and quantify the different types of cell deaths induced by the presence of intracellular superoxide anions (. O2 - ) and hydrogen peroxide (H2 O2 ) ROS generated in situ upon NIR irradiation.

Polymer functionalized gold nanoparticles as nonviral gene delivery reagents.

BACKGROUND: In the present study, we investigated the ability of polyethylene glycol (PEG) functionalized gold nanoparticles to function as nonviral vectors in the transfection of different cell lines, comparing them with commercial lipoplexes. METHODS: Positively-charged gold nanoparticles were synthesized using polyethylenimine (PEI) as a reducing and stabilizer agent and its cytotoxicity was reduced by its functionalization with PEG. We bound the nanoparticles to three plasmids with different sizes (4-40 kpb). Vector internalization was evaluated by confocal and electronic microscopy. Its transfection efficacy was studied by fluorescence microscopy and flow cytometry. The application of the resulting vector in gene therapy was evaluated indirectly using ganciclovir in HeLa cells transfected to express the herpes virus thymidine kinase. RESULTS: An appropriate ratio between the nitrogen from the PEI and the phosphorous from the phosphate groups of the DNA, together with a reduced size and an elevated electrokinetic potential, are responsible for an increased nanoparticle internalization and enhanced protein expression when carrying plasmids of up to 40 kbp (plasmid size close to the limit of the DNA-carrying capacity of viral vectors). Compared to a commercial transfection reagent, an equal or even higher expression of reporter genes (on HeLa and Hek293t) and a suicide effect on HeLa cells transfected with the herpes virus thymidine kinase gene were observed when using this novel nanoparticulated vector. CONCLUSIONS: Nonviral vectors based on gold nanoparticles covalently coupled with PEG and PEI can be used as efficient transfection reagents showing expression levels that are the same or greater than those obtained with commercially available lipoplexes.

Nitrogen-Induced Transformation of Vitamin†C into Multifunctional Up-converting Carbon Nanodots in the Visible-NIR Range.

Water-soluble, biocompatible, and photoluminescent carbon nanodots have been obtained from the rationalized carbonization of vitamin C, a well-known antioxidant molecule in the presence of an amine co-reactant. Herein, we describe the positive influence of N-doping to induce a unique pH-dependent lifetime decay response that would be potentially attractive in biological backgrounds with intrinsic fluorescence fluctuations. In addition, the selectivity and sensitivity of the N-containing carbon nanoprobes towards the detection of copper ions at ppm levels is critically enhanced in comparison with the un-doped counterpart, especially in the near-infrared (NIR) range. Finally, the up-converting properties have been also successfully applied to image tumor cells in the visible range and remarkably, in the NIR region in which minimal tissue or water absorption and maximum penetration depth are expected.

Single-step endoscopic ultrasonography-guided drainage of peripancreatic fluid collections with a single self-expandable metal stent and standard linear echoendoscope.

Endoscopic ultrasonography (EUS)-guided drainage of peripancreatic fluid collections (PFCs) is a well described alternative to surgery or percutaneous drainage. However, it is limited by the requirement for a large working channel that allows multiple plastic stent placement, which is only commercially available on therapeutic linear echoendoscopes. Herein, we describe the drainage of PFCs with a single self-expandable metal stent (SEMS) using a single-step technique and standard linear echoendoscope. Seven cases were identified during a retrospective chart review, and included all patients who had undergone EUS-guided drainage of PFCs during a 6-month period. The mean age was 46 years (range 25 - 70 years) and all patients were symptomatic. The mean diameter of PFCs was 8 cm (range 4.1 - 12.5 cm). Previous percutaneous drainage had failed in three patients. A total of 10 PFCs were drained. Three patients had two cysts drained by the same stent and one patient had two separate procedures to drain two distinct cysts. The SEMS was in place for a mean of 13 weeks (range 4 - 34 weeks). Successful placement of SEMS was achieved in all seven cases. Patients were followed for a mean of 18 weeks (range 7 - 35 weeks), and symptom improvement was achieved in all cases. Complete resolution of PFC was achieved in 9 /10 cysts. No complications were encountered. Single-step EUS-guided drainage of PFCs using a single 10-mm SEMS and a standard linear echoendoscope appears to be a feasible endoscopic technique with excellent technical and clinical success rates.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of extra-pulmonary tuberculosis.

SETTING: The incidence of extra-pulmonary tuberculosis (EPTB) is surprisingly high among certain subgroups of patients in industrialized countries. Diagnosis is often difficult and can require costly invasive workup. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe, minimally invasive, accurate, out-patient diagnostic modality for assessing mediastinal and abdominal lymphadenopathy and masses. OBJECTIVE: To evaluate the usefulness of EUS-FNA for diagnosing EPTB. DESIGN: Retrospective 6-year review, including all patients who had evidence of lymphadenopathy or mass on computed tomography scan accessible by EUS and consideration of tuberculosis (TB) in the differential diagnosis. RESULTS: Of 81 potential patients, a total of 20 cases with EPTB diagnosed by EUS-FNA were identified. Necrotizing granulomas had a 58% likelihood of TB vs. 14% for other cytologic findings (P < 0.0001); necrosis was also predictive, with a 44% likelihood of TB vs. 19% (P < 0.0225). EUS-FNA cytology was diagnostic for TB when an African-born patient had necrotizing granulomas (P < 0.0001), and was highly suggestive with necrosis alone (P < 0.0514). Non-necrotizing granulomas were not predictive of TB and an alternative diagnosis was more likely, including sarcoidosis and cancer. CONCLUSION: EUS-FNA is a useful diagnostic modality that should be used early in the diagnostic workup of suspected EPTB.