Subject(s)
Antineoplastic Agents/administration & dosage , Chemotaxis , Liposomes/administration & dosage , Magnetosomes , Neoplasms/drug therapy , Oxygen/metabolism , Tumor Hypoxia/physiology , Aerobiosis/physiology , Animals , Chemotaxis/physiology , Drug Carriers/chemistry , Drug Compounding , Drug Delivery Systems , Gram-Negative Anaerobic Cocci/metabolism , HCT116 Cells , Humans , Liposomes/pharmacokinetics , Magnetosomes/chemistry , Magnetosomes/metabolism , Mice , Nanoparticles/administration & dosage , Neoplasms/metabolism , Xenograft Model Antitumor AssaysABSTRACT
Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, Magnetococcus marinus strain MC-1 (ref. 4), can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrations based on a two-state aerotactic sensing system. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in severe combined immunodeficient beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.
Subject(s)
Alphaproteobacteria , Colorectal Neoplasms/drug therapy , Drug Delivery Systems/methods , Ferric Compounds , Magnetic Fields , Nanoparticles/chemistry , Neoplasms, Experimental/drug therapy , Animals , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Ferric Compounds/chemistry , Ferric Compounds/pharmacology , HCT116 Cells , Humans , Hypoxia/drug therapy , Hypoxia/metabolism , Hypoxia/pathology , Mice , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Rats , Xenograft Model Antitumor AssaysABSTRACT
STUDY DESIGN: Radiographic software measurement analysis in adult scoliosis. OBJECTIVE: To assess the accuracy as well as the intra- and interobserver reliability of measuring different indices on preoperative adult scoliosis radiographs using a novel measurement software that includes a calibration procedure and semiautomatic features to facilitate the measurement process. SUMMARY OF BACKGROUND DATA: Scoliosis requires a careful radiographic evaluation to assess the deformity. Manual and computer radiographic process measures have been studied extensively to determine the reliability and reproducibility in adolescent idiopathic scoliosis. Most studies rely on comparing given measurements, which are repeated by the same user or by an expert user. A given measure with a small intra- or interobserver error might be deemed as good repeatability, but all measurements might not be truly accurate because the ground-truth value is often unknown. Thorough accuracy assessment of radiographic measures is necessary to assess scoliotic deformities, compare these measures at different stages or to permit valid multicenter studies. METHODS: Thirty-four sets of adult scoliosis digital radiographs were measured two times by three independent observers using a novel radiographic measurement software that includes semiautomatic features to facilitate the measurement process. Twenty different measures taken from the Spinal Deformity Study Group radiographic measurement manual were performed on the coronal and sagittal images. Intra- and intermeasurer reliability for each measure was assessed. The accuracy of the measurement software was also assessed using a physical spine model in six different scoliotic configurations as a true reference. RESULTS: The majority of the measures demonstrated good to excellent intra- and intermeasurer reliability, except for sacral obliquity. The standard variation of all the measures was very small: ≤ 4.2° for Cobb angles, ≤ 4.2° for the kyphosis, ≤ 5.7° for the lordosis, ≤ 3.9° for the pelvic angles, and ≤5.3° for the sacral angles. The variability in the linear measurements (distances) was <4 mm. The variance of the measures was 1.7 and 2.6 times greater, respectively, for the angular and linear measures between the inter- and intrameasurer reliability. The image quality positively influenced the intermeasurer reliability especially for the proximal thoracic Cobb angle, T10-L2 lordosis, sacral slope and L5 seating. The accuracy study revealed that on average the difference in the angular measures was < 2° for the Cobb angles, and < 4° for the other angles, except T2-T12 kyphosis (5.3°). The linear measures were all <3.5 mm difference on average. CONCLUSION: The majority of the measures, which were analyzed in this study demonstrated good to excellent reliability and accuracy. The novel semiautomatic measurement software can be recommended for use for clinical, research or multicenter study purposes.
