Abstract
In cancer, the use of microbots based on anaerobic bacteria as specific transporters targeting tumor tissues has been explored since most solid tumors exhibit hypoxic regions. The aim of this study was to develop and characterize magnetic microbots based on Bifidobacteria and iron oxide fluorescent magnetic nanoparticles complexed with chitosan and a hypoxia inducible plasmid. In addition, the efficiency of the microbots for gene delivery to solid tumors was evaluated in an in vivo model by florescence and luminescence. To elaborate microbots, iron oxide fluorescent magnetic nanoparticles complexed with chitosan and a hypoxia-inducible plasmid called nanocomplex (NCs) with a size of 302 nm and a ζ potential of +16 mV were obtained and loaded onto Bifidobacteria membranes. Microbots with a diameter between 1–2 µm were characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). Microbots were injected intravenously through the tail vein to tumor-bearing mice, and then a magnet was placed to focus them to the tumor area. Forty-eight hours after injection, the biodistribution was determined by florescence and luminescence. The greatest luminescence and fluorescence emitted were found in tumor tissue compared with the normal organs. We created a vector that can be directed by a magnet and deliver genes whose expression is regulated by hypoxic microenvironment of tumor.
Highlights
Cancer is a major disease that causes death worldwide [1,2], and current traditional strategies against cancer and other diseases of global importance have certain disadvantages such as a lack of tumor selectivity, nonspecific toxicity, and resistance to multiple drugs [3]
We show the use of microbots based on Bifidobacteria and magnetic nanoparticles for gene delivery to a tumor in an in vivo model
Intransporters cancer, the use of microbots based on has anaerobic bacteria as specific that allow themexplored to reach specific tissues, barriers transporterscomplex targetedmechanisms to tumor tissues has been since they havecross morenonpermeable complex and modulate their microenvironment
Summary
Cancer is a major disease that causes death worldwide [1,2], and current traditional strategies against cancer and other diseases of global importance have certain disadvantages such as a lack of tumor selectivity, nonspecific toxicity, and resistance to multiple drugs [3]. Among the approaches used in the development of cancer therapies, great expectations have been generated in systems based on living cells [6], since they have more complex mechanisms that allow them to cross non-permeable barriers, modulate their microenvironment, and reach specific tissues. Due to these unique characteristics, living cells have been considered as a new class of vectors with high specificity and long persistence [7]. Nanostructures are carried either within or on the surface of the bacterial membrane for the delivery of therapeutic loads in the cell [10]
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