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Biodegradable nanoparticle-mediated K-ras siRNA delivery has shown inhibition of cell proliferation, migration and invasion in pancreatic cancer cells.

Biodegradable polymer nanoplexes were used as siRNA carriers for interleukin-8 gene silencing to attenuate cell proliferation in pancreatic cancer cells.

Biofunctionalized quantum dots (QDs), especially protein-coated QDs, are known to be useful targeted fluorescent labels for cellular and deep-tissue imaging. These nanoparticles can also serve as efficient energy donors in fluorescence resonance energy transfer (FRET) binding assays for the multiplexed sensing of tumor markers. However, current preparation processes for protein-functionalized QDs are laborious and require multiple synthesis steps (e.g. preparing them in high temperature, making them dispersible in water, and functionalizing them with surface ligands) to obtain a high quality and quantity of QD formulations, significantly impeding the progress of employing QDs for clinical diagnostics use such as a QD-based immunohistofluorescence assay. Herein, we demonstrate a one-step synthesis approach for preparing protein-functionalized QDs using a microfluidic (MF) chip setup. Using bovine serum albumin (BSA) molecules as the surface ligand model, we first studied and optimized the MF reaction synthesis parameters (e.g. reaction temperature, and channel width and length) for making protein-functionalized QDs using COMSOL simulation modeling, followed by experimental verification. Moreover, in comparison with the BSA-functionalized QDs synthesized using the conventional bench-top method, BSA-QDs prepared using the MF approach exhibit a significantly higher protein-functionalization efficiency, photostability and colloidal stability. The proposed one-step MF synthesis approach provides a rapid, cost effective, and a small-scale production of nanocrystals platform for developing new QD formulations in applications ranging from cell labeling to biomolecular sensing. Most importantly, this approach will considerably reduce the amount of chemical waste generated during the trial-and-error stage of developing and perfecting the desired physical and optical properties of new QD materials.

Transition metal dichalcogenides (TMDCs) are categorized as novel two-dimensional (2D) nanomaterials with unique physical and chemical properties, bearing varied applications in medical and materials sciences. However, only a few works report the application of TMDCs for gene therapy in cancer treatment. Here, we engineer a multi-gene delivery system based on functionalized monolayer MoS2, which can co-deliver HDAC1 and KRAS small interfering RNAs (siRNAs) to Panc-1 cancer cells for combinational cancer therapy. The synergistic effect of gene silencing therapy and NIR phototherapy is demonstrated by inhibition of both genes, in vitro cell growth rate, and in vivo tumor volume growth rate, exemplifying pre-eminent anticancer efficacy. This anti-tumor effect is a result of the photothermal effect of MoS2 induced by NIR excitation and inactivation of HDAC1 and KRAS genes, which consequently bring about apoptosis, inhibit migration, and induce cell cycle arrest in the treated Panc-1 cells. Moreover, good biocompatibility and reduced cytotoxicity of MoS2-based nanocarriers enable their metabolism within in vitro and in vivo mouse models over a prolonged duration without any evident ill-effects. In summary, we demonstrate the promising potential of low-toxicity, functionalized MoS2 nanocarriers as a biocompatible gene delivery system for in vivo pancreatic adenocarcinoma therapy.

Background and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT.Methods This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH).Results Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not asComorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013).Conclusions Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

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