期刊
ACS NANO
卷 9, 期 6, 页码 6158-6167出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b01426
关键词
porous silicon; oral drug delivery; C. elegans; A. ceylanicum; hookworm; Bacillus thuringiensis (Bt); crystal protein
类别
资金
- National Science Foundation [DMR-1210417]
- National Institute of Allergy and Infectious Diseases, NIH [2R01AI056189]
- Defense Advanced Research Projects Agency (DARPA) [HR0011-13-2-0017]
- Division Of Materials Research
- Direct For Mathematical & Physical Scien [1210417] Funding Source: National Science Foundation
The ability of nano- and microparticles of partially oxidized mesoporous silicon (pSi) to sequester, protect, and deliver the anthelmintic pore-forming protein Cry5B to nematodes is assessed in vitro and in vivo. Thermally oxidized pSi particles are stable under gastric conditions and show relatively low toxicity to nematodes. Fluorescence images of rhodannine-labeled pSi particles within the nematodes Caenorhabditis elegans and Ancylostoma ceylanicum show that ingestion is dependent on particle size: particles of a 0.4 +/- 0.2 mu m size are noticeably ingested by both species within 2 h of introduction in vitro, whereas 5 +/- 2 mu m particles are excluded from C. elegans but enter the pharynx region of A. ceylanicum after 24 h. The anthelmintic protein Cry5B, a pore-forming crystal (Cry) protein derived from Bacillus thuringiensis, is incorporated into the pSi particles by aqueous infiltration. Feeding of Cry5B-loaded pSi particles to C. elegans leads to significant intoxication of the nematode. Protein-loaded particles of size 0.4 urn display the highest level of in vitro toxicity toward C. elegans on a drug-mass basis. The porous nanostructure protects Cry5B from hydrolytic and enzymatic (pepsin) degradation in simulated gastric fluid (pH 1.2) for time periods up to 2 h. In vivo experiments with hookworm-infected hamsters show no significant reduction in worm burden with the Cry5B-loaded particles, which is attributed to slow release of the protein from the particles and/or short residence time of the particles in the duodenum of the animal.
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