{"id":55955,"date":"2017-10-23T11:04:06","date_gmt":"2017-10-23T09:04:06","guid":{"rendered":"http:\/\/ibecbarcelona.eu\/?page_id=55955"},"modified":"2026-01-16T14:40:06","modified_gmt":"2026-01-16T13:40:06","slug":"targeted-therapeutics-and-nanodevices","status":"publish","type":"page","link":"https:\/\/ibecbarcelona.eu\/ca\/targeted-therapeutics","title":{"rendered":"Targeted therapeutics and nanodevices"},"content":{"rendered":"
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About<\/h2>\n
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Currently, a myriad of drug carriers<\/strong> or delivery systems<\/strong> have been developed to improve the overall performance and safety of therapeutic agents. However, our ability to treat neurological maladies, genetic syndromes, cancer, etc., remains a major challenge. One of the prime obstacles is our limited knowledge on the biological parameters that regulate the interaction of these systems with our tissues and, hence, our inability to gain non-invasive, efficient, and specific access within the body, its cells, and subcellular organelles.<\/h4>\n\n\n\n
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To generate knowledge and tools to overcome this obstacle, we study the biological mechanisms ruling how our cells and tissues transport cargoes to precise destinations within our bodies and apply this knowledge to the design of nanodevices for improved delivery of therapeutic agents to specific disease sites.<\/p>\n<\/blockquote>\n\n\n\n

Biologically-Controlled Transport of Drug Carriers<\/strong><\/h2>\n\n\n\n

Most current strategies aim to bind a drug nanocarrier to a specific cell-surface receptor; but after said binding takes place, receptor-associated signaling and transport processes take control. Instead, our laboratory can impart a drug carrier control over the biological events that occur beyond binding. We have shown how using the same receptor, the kinetics, mechanism, and destination of a drug carrier can be modulated by: (a) varying its size, shape, and targeting valency; (b) varying the receptor epitope to which the carrier binds; (c) coupling carriers to signaling molecules; (d) combining targeting to several receptors; or (e) coupling targeting moieties with anti-phagocytic moieties on the surface of drug carriers.  <\/span><\/p>\n\n\n\n

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Transport of Drug Carriers Across Physiological Barriers<\/strong><\/h2>\n\n\n\n

<\/b>Crossing the linings that separate body and cellular compartments is paramount for efficient drug delivery<\/span><\/span>. <\/span><\/span>We <\/span><\/span>were f<\/span><\/span>irst <\/span><\/span>to <\/span><\/span>identif<\/span><\/span>y<\/span><\/span> a natural pathway regulated by <\/span><\/span>ICAM-1<\/span><\/span>, a cell adhesion molecule overexpressed by most cells under pathological states,<\/span><\/span> <\/span><\/span>which<\/span><\/span> enables transcytosis across <\/span><\/span>the<\/span><\/span> epithelial barrier <\/span><\/span>that <\/span><\/span>separates the gastrointestinal tract from the bloodstream<\/span><\/span> <\/span><\/span>for <\/span><\/span>oral<\/span><\/span> delivery, and <\/span><\/span>the <\/span><\/span>blood-brain barrier <\/span><\/span>that separates the bloodstream from the brain tissue<\/span><\/span> for <\/span><\/span>delivery<\/span><\/span> of therapeutics against neurological diseases<\/span><\/span>. We<\/span><\/span> also work with <\/span><\/span>DNA-built <\/span><\/span>nanocarriers<\/span><\/span> <\/span><\/span>which<\/span><\/span> enable<\/span><\/span> uptake within cells and<\/span><\/span> endosomal escape <\/span><\/span>for<\/span><\/span> delivery <\/span><\/span>to the cytosol and other subcellular compartments. <\/span><\/span> <\/span><\/p>\n\n\n\n

Figure 1<\/em>. ICAM-1-targeted nanocarriers (anti-ICAM NCs) crossing the blood-brain barrier in an animal model.<\/strong> Fluorescence microscopy of cortical brain samples isolated from mice 30 min or 3 h after intravenous injection with green-fluorescent anti-ICAM NCs or control IgG NCs. Scale bar = 10 \u03bcm. Boxes = regions magnified 3-fold in the right panels. Arrows = NCs on the blood-facing surface of the blood-brain barrier. Open arrowheads = NCs on the brain-facing surface of the blood-brain barrier. Closed arrowheads = NCs inside of brain endothelial cells. Extracted from Manthe et al., Intertwined mechanisms define transport of anti-ICAM nanocarriers across the endothelium and brain delivery of a therapeutic enzyme. J Control Rel. 324 (2020):181-193).<\/em><\/h6>\n\n\n\n

Improving Treatment of Lysosomal Disorders<\/strong><\/h2>\n\n\n\n

<\/b>P<\/span><\/span>athologies due to <\/span><\/span>mono<\/span><\/span>gen<\/span><\/span>ic<\/span><\/span> deficienc<\/span><\/span>ies<\/span><\/span>, such as the case of lysosomal disorders, are valuable models to study disease progression and therapeutic intervention because <\/span><\/span>of their<\/span><\/span> well-known etiology<\/span><\/span>, <\/span><\/span>unequivocal diagnosis<\/span><\/span>, and <\/span><\/span>availability regarding <\/span><\/span>patient samples, diverse cell types, and animal models. Since these diseases <\/span><\/span>associate to<\/span><\/span> either acute or long-term effects depending on genetic severity, and <\/span><\/span>they <\/span><\/span>associate with neurodegeneration, cardiovascular, metabolic, and cancer-like syndromes, they represent excellent disease <\/span><\/span>models. Consequently, we are applying <\/span><\/span>targeted nanotechnology concepts to the treatment of genetic lysosomal disorders. Current therapies by <\/span><\/span>i.v.<\/span><\/span> enzyme infusion <\/span><\/span>are<\/span><\/span> only helpful for diseases where clearance cells and organs (liver, spleen, macrophages, etc.) are the main targets. Yet, delivery to other organs <\/span><\/span>such as the <\/span><\/span>brain, lungs, etc. hinders <\/span><\/span>treatment <\/span><\/span>for most <\/span><\/span>of these d<\/span><\/span>iseases. Using <\/span><\/span>types<\/span><\/span> A and B Niemann-Pick, Fabry, and Gaucher diseases as examples, we <\/span><\/span>are <\/span><\/span>developing new therapeutic strategies to <\/span><\/span>deliver therapeutic enzymes to all affected organs in animal models, <\/span><\/span>which <\/span><\/span>hold<\/span><\/span>s<\/span><\/span> considerable translational potential.<\/span><\/span> <\/span><\/p>\n\n\n\n

Figure 2<\/em>. ICAM-1 targeted DNA-made nanocarriers (anti-ICAM\/3DNA) for drug delivery to the lungs.<\/strong> Cy3-labeled 3DNA targeted to ICAM-1 (anti-ICAM\/Cy3-3DNA) or non-targeted controls (IgG\/Cy3-3DNA) were intravenously injected in mice. Lungs were isolated and processed at sacrifice at 60 min. (A) Confocal microscopy shows Cy3 3DNA (red), while the targeting coat (antibody) is visualized using a FITC-secondary antibody (green). Arrowheads show colocalization of the antibody on the coat of 3DNA. (B) Confocal microscopy showing anti-ICAM\/Cy3-3DNA (red) and lung endothelial cells visualized using polyclonal anti-PECAM-1+FITC-secondary antibody (green). Arrows indicate colocalization of Cy3-3DNA with endothelial PECAM-1. (Extracted from Roki et al, Unprecedently high targeting specific to lung ICAM-1 using 3DNA nanocarriers. J Control Release. 305 (2019):41-49<\/em>).<\/h6>\n\n\n\n
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Figure 1<\/figcaption><\/figure>\n\n\n\n
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Figure 2<\/figcaption><\/figure>\n<\/figure>\n\n\n\n<\/div>

Staff<\/h2>\n
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