Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo

Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease-specific manner represents a potentially powerful technology. Using prostate cancer as a model, we report docetaxel (Dtxl)-encapsulated nanoparticles formulated with biocompatible and biodegradable poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) copolymer and surface functionalized with the A10 2′-fluoropyrimidine RNA aptamers that recognize the extracellular domain of the prostate-specific membrane antigen (PSMA), a well characterized antigen expressed on the surface of prostate cancer cells. These Dtxl-encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-Apt) bind to the PSMA protein expressed on the surface of LNCaP prostate epithelial cells and get taken up by these cells resulting in significantly enhanced in vitro cellular toxicity as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP) (P < 0.0004). The Dtxl-NP-Apt bioconjugates also exhibit remarkable efficacy and reduced toxicity as measured by mean body weight loss (BWL) in vivo [body weight loss of 7.7 ± 4% vs. 18 ± 5% for Dtxl-NP-Apt vs. Dtxl-NP at nadir, respectively (mean ± SD); n = 7]. After a single intratumoral injection of Dtxl-NP-Apt bioconjugates, complete tumor reduction was observed in five of seven LNCaP xenograft nude mice (initial tumor volume of ≈300 mm(3)), and 100% of these animals survived our 109-day study. In contrast, two of seven mice in the Dtxl-NP group had complete tumor reduction with 109-day survivability of only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles without drug were similarly nonefficacious. This report demonstrates the potential utility of nanoparticle-aptamer bioconjugates for a therapeutic application

Co-located offshore wind and tidal stream turbines: Assessment of energy yield and loading

Co-location of wind 1 and tidal stream turbines provides opportunity for improved economic viability of electricity generation from these resources relative to projects exploiting each resource separately. Here co-deployment is assessed in terms of energy generation and loading of support structures. Energy yield is modelled using an eddy viscosity wake model for wind turbines and superposition of self-similar wake for tidal turbines. A case-study of the Inner Sound of the Pentland Firth is considered. For 3.5 years of coincident resource data, 12MW wind capacity co-located with a 20MW tidal array results in a 70% increase in energy yield, compared to operating the tidal turbines alone. Environmental loads are modelled for a braced monopile structure supporting both a wind and tidal turbine, as well as for each system in isolation. Peak loading of the combined system is found to be driven by wind loads with greatest overturning moment occurring with the wind turbine operating at close to rated-speed and the tidal turbine close to its shutdown speed. Mean loads vary across the tidal array by 4.5% indicating no significant shielding effects are gained by co-locating in more sheltered regions of the array