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.
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)].
There is concern that cotton gins located in boll weevil, Anthonomus grandis grandisBoheman, 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 ≈100-3,700 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. KeywordsAnthonomus grandis grandis, boll weevil, cotton gin, cotton module, eradication RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. ABSTRACT 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 Þelds in three distinct areas of Texas and found that weevils can be present in large numbers in cotton Þelds 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 Ϸ100 Ð3,700 adult boll weevils were packed inside modules constructed at the sampled Þelds. Marked weevils were forced through a laboratory Þeld 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 u...
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