Functional polyesters enable selective siRNA delivery to lung cancer over matched normal cells.

Conventional chemotherapeutics nonselectively kill all rapidly dividing cells, which produces numerous side effects. To address this challenge, we report the discovery of functional polyesters that are capable of delivering siRNA drugs selectively to lung cancer cells and not to normal lung cells. Selective polyplex nanoparticles (NPs) were identified by high-throughput library screening on a unique pair of matched cancer/normal cell lines obtained from a single patient. Selective NPs promoted rapid endocytosis into HCC4017 cancer cells, but were arrested at the membrane of HBEC30-KT normal cells during the initial transfection period. When injected into tumor xenografts in mice, cancer-selective NPs were retained in tumors for over 1 wk, whereas nonselective NPs were cleared within hours. This translated to improved siRNA-mediated cancer cell apoptosis and significant suppression of tumor growth. Selective NPs were also able to mediate gene silencing in xenograft and orthotopic tumors via i.v. injection or aerosol inhalation, respectively. Importantly, this work highlights that different cells respond differentially to the same drug carrier, an important factor that should be considered in the design and evaluation of all NP carriers. Because no targeting ligands are required, these functional polyester NPs provide an exciting alternative approach for selective drug delivery to tumor cells that may improve efficacy and reduce adverse side effects of cancer therapies.

Chemical cotton stalk destruction for maintenance of host-free periods for the control of overwintering boll weevil in tropical and subtropical climates.

In the Lower Rio Grande Valley (LRGV) of Texas, cotton regrows and produces fruit from undestroyed stalks throughout the winter, and in spring weevils from such locations become a serious threat. The success of the boll weevil eradication program, which was reintroduced in the LRGV in 2005, will be dependent on thorough stalk destruction following harvest. However, adverse weather conditions and conservation tillage often impede immediate and complete stalk destruction using typical tool implements, and alternative stalk control methods are needed. This study provides an examination of the efficacy for cotton stalk destruction of different herbicides (thifensulfuron-methyl + tribenuron-methyl, dicamba-diolamine, 2,4-D-dimethylammonium, flumioxazin, 2,4-DB-dimethylammonium and carfentrazone-ethyl) and their rates, spray volumes and application timings on shredded or standing cotton stalks after stripper or picker harvest. None of the tested herbicides, except 2,4-D-dimethylammonium, stopped post-harvest cotton regrowth and fruiting. 2,4-D-dimethylammonium sprayed once (0 or 7 days) after cotton was harvested at 1 lb AE acre(-1) (1.12 kg ha(-1)), in a spray volume of 10 gal water acre(-1) (93.5 L ha(-1)) with 5 mL L(-1) surfactant, was highly effective in stalk destruction (72-90%). The best results were achieved when the herbicide was applied immediately after the cotton was shredded, followed by standing stripper-harvested and standing picker-harvested cotton. 2,4-D-dimethylammonium applied twice, 0 and 14 (or 21) days after cotton harvest, was 100% effective in killing stalks, regardless of whether they were shredded or standing, or whether harvest was by stripper or picker. These findings showed that 2,4-D-dimethylammonium cotton stalk destruction eliminated food and reproductive opportunities for managing overwintering boll weevils [Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae)].

Dispersal of boll weevils (Coleoptera: Curculionidae) from cotton modules before ginning.

We characterized the level of risk of boll weevil, Anthonomus grandis grandis Boheman, reintroduction to an eradication zone posed by dispersal from cotton modules during and after transport to the gin. Mark-release-recapture experiments in August and September in Texas indicated that most weevils disperse rapidly from the module surface, temperature permitting, unless confined under a module tarp, where most died. Nevertheless, 1-5% of released weevils were recovered alive after 24 h on the side and top surfaces of modules, representing potential dispersants. Mortality of boll weevils caged on the top surface of a module was 95-100% after 1-4 d when maximum air temperatures were > or = 33 degrees C and 72-100% when minimum temperatures were -7 degrees C or lower, but a few survived even after experiencing a minimum daily temperature of -12 degrees C. Under warm (daily maximum temperatures > or = 25 degrees C) and cold (daily minimum temperatures < or = 0 degrees C) weather conditions, survival was higher under the tarp than on the open surface of the module (20 versus 7% and 42 versus 26%, respectively), but mortality was 100% in both locations when temperatures reached 34 degrees C. Our results indicate that although the threat to an eradication zone posed by boll weevil dispersal from an infested module is very low under most environmental conditions, it is probably greatest when 1) a module is constructed and transported from an infested zone during weather too cool for flight, followed by warm weather favorable for flight at the gin yard; or 2) such a module is transported immediately after construction in moderate-to-warm weather.

Effects of insecticides and defoliants applied alone and in combination for control of overwintering boll weevil (Anthonomus grandis; Coleoptera: Curculionidae)--laboratory and field studies.

In laboratory, greenhouse and field tests, we determined the effects of combining full rates of the defoliants tribufos and thidiazuron and the herbicide thifensulfuron-methyl with half rates of the insecticides lambda-cyhalothrin or azinphos-methyl, and the combination of tribufos and thidiazuron, both in half rates, on mortality of the boll weevil, Anthonomus grandis grandis Boheman and on the quality of defoliation. Tribufos, 0.47 kg ha(-1) and tribufos, 0.235 kg ha(-1) + thidiazuron, 0.125 kg ha(-1) exhibited a slightly toxic effect to boll weevil, while tribufos, 0.47 kg ha(-1) + lambda-cyhalothrin, 0.019 kg ha(-1), tribufos, 0.47 kg ha(-1) + azinphos-methyl, 0.14 kg ha(-1), and tribufos, 0.235 kg ha(-1) + thidiazuron, 0.125 kg ha(-1) + azinphos-methyl, 0.14 kg ha(-l), provided control of boll weevil as good as or better than full-rate azinphos-methyl or lambda-cyhalothrin alone owing to synergistic effects. Thidiazuron or thifensulfuron-methyl alone or in combination with insecticides did not affect boll weevil mortality. Treatment with tribufos + thidiazuron, both at half rate, significantly increased defoliation compared to full rates of tribufos or thidiazuron alone, and provided adequate defoliation for approximately the same cost per hectare.

Potential for transport of boll weevils (Coleoptera: Curculionidae) to the cotton gin within cotton modules.

There is concern that cotton gins located in boll weevil, Anthonomus grandis grandis Boheman, eradication zones serving customers in adjacent infested zones may serve as a site for boll weevil reintroductions if weevils are transported alive inside cotton modules. We surveyed fields in three distinct areas of Texas and found that weevils can be present in large numbers in cotton fields that have been defoliated and desiccated in preparation for harvest, both as free adults and as immatures inside unopened bolls. Harvested cotton taken from module builders indicated that approximately = 100-3700 adult boll weevils were packed inside modules constructed at the sampled fields. Marked weevils were forced through a laboratory field cleaner (bur extractor) commonly mounted on stripper-harvesters, and 14% were recovered alive in the seed cotton fraction and lived at least to 24 h. Survival of weevils placed inside modules declined over time up to 7 d, but the magnitude of the decline varied with experimental conditions. In one experiment, 91% of the weevils survived to 7 d, whereas under harsher environmental conditions, only 11% survived that long. Together, our results indicate that when cotton is harvested in an infested area, boll weevils likely will be packed alive into cotton modules, and many will still be alive by the time the module is fed into the gin, at least up to 7 d after the module's construction.