Oxygen depleted hypoxic regions in the tumour are generally resistant to therapies1. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour2 of magnetotactic bacteria3, Magnetococcus marinus strain MC-14, 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 nanocrystals5, tend to swim along local magnetic field lines and towards low oxygen concentrations6 based on a two-state aerotactic sensing system2. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in SCID 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.

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Layer-by-layer self-assembly of two polysaccharides, hyaluronan (HA) and chitosan (CH), was employed to engineer bioactive coatings for endovascular stents. A polyethyleneimine (PEI) primer layer was adsorbed on the metallic surface to initiate the sequential adsorption of the weak polyelectrolytes. The multilayer growth was monitored using a radiolabeled HA and shown to be linear as a function of the number of layers. The chemical structure, interfacial properties, and morphology of the self-assembled multilayer were investigated by time-of-flight secondary ions mass spectrometry (ToF-SIMS), contact angle measurements, and atomic force microscopy (AFM), respectively. Multilayer-coated NiTi disks presented enhanced antifouling properties, compared to unmodified NiTi disks, as demonstrated by a decrease of platelet adhesion in an in vitro assay (38% reduction; p = 0.036). An ex vivo assay on a porcine model indicated that the coating did not prevent fouling by neutrophils. To assess whether the multilayers may be exploited as in situ drug delivery systems, the nitric-oxide-donor sodium nitroprusside (SNP) was incorporated within the multilayer. SNP-doped multilayers were shown to further reduce platelet adhesion, compared to standard multilayers (40% reduction). When NiTi wires coated with a multilayer containing a fluorescently labeled HA were placed in intimate contact with the vascular wall, the polysaccharide translocated on the porcine aortic samples, as shown by confocal microscopy observation of a treated artery. The enhanced thromboresistance of the self-assembled multilayer together with the antiinflammatory and wound healing properties of hyaluronan and chitosan are expected to reduce the neointimal hyperplasia associated with stent implantation.