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Nanocapsules “3-in-1” for in vivo biomedical imaging: an ICMAB and VHIR study

An interdisciplinary research group synthesizes drug delivery nanocapsules with three contrast agents for three biomedical imaging techniques to study their biodistribution. The approach is modular and allows including the contrast agents together or separately on the nanocapsules, without affecting their size or shape, nor interfering with the encapsulated therapeutic agent. The study is co-led by researchers from VHIR and ICMAB-CSIC, and is part of a European project (MAGBBRIS) to prepare safe, biocompatible and biodegradable nanomaterials for biomedical imaging and brain repair after stroke.

Nanomedicine is largely focused on the design of nanosystems as diagnostic and therapeutic tools (teragnosis), i.e. on the design of nanomaterials for the identification of pathologies using biomedical imaging techniques, and for the control release of therapeutic agents for its treatment.

A research group from the Institute of Materials Science of Barcelona (ICMAB-CSIC) and the Vall d'Hebron Research Institute (VHIR), in collaboration with CICbiomaGUNE (Basque Country) and the University of Artois ( France), have developed nanocapsules that can be administered intravenously and their biodistribution in vivo can be visualized using three different medical imaging techniques.

Nanocapsules are used for drug delivery of insoluble, highly sensitive, or multi-components drugs. Nanocapsules also protect the encapsulated drug from degradation, inactivation or clearance, and reduce its toxicity, if it is the case. Furthermore, nanocapsules allow the functionalization or modification of its surface, so contrast agents for biomedical imaging can be chemically attached, as is the case in this study.

The biomedical imaging techniques used in this study include magnetic resonance imaging (MRI), fluorescence (blue and near-infrared) and positron emission tomography (PET). All three are non-invasive diagnostic by imaging and experimental research tools that allow to visualize where the nanocapsules are in the organisms in real time.

Figure: Nanocapsule with the three contrast agents in the shell and the therapeutic agent in the inside. 

Using more than one contrast agent to study the in vivo biodistribution of a nanodrug provides additional information, since the three imaging techniques have different sensitivity and resolution limits, and can be used at different levels of drug development, or to detect biodistribution in different tissues of the human body.

The nanocapsules are made of a biodegradable and biocompatible biopolymer, PLGA (poly (lactic-co-glycolic acid)), approved by the FDA (United States Food and Drug Administration). The study confirms that they are safe both in vivo and in vitro.

Furthermore, the particularity of the nanocapsules synthesized in this study is that they have been functionalized in a modular way, since the three imaging probes can be added and removed separately or simultaneously. "This fact allows that in each nanodrug development, a different imaging technique can be used to validate the results" explains Anna Roig, researcher who leads the study at the ICMAB.

These contrast agents are used in all three biomedical imaging techniques, maintaining the size and shape of the nanocapsules, and without cross interference with the others or with the drug encapsulated inside the nanocapsule.

"A great challenge in nanomedicine is how to make a local non-invasive administration of nanomaterials with a controlled release of the therapeutic agent, especially in difficult-access tissues, such as the brain. Thus, having new biocompatible formulations that allow in vivo neuroimaging monitoring are necessary in pre-clinical research phases to assess the development of specific treatments", explains Anna Rosell, researcher who leads the study at VHIR.

"To succeed in translating nanomaterials prepared in the laboratory into clinical trials, we must synthesize nanomaterials as simply as possible for their final application. This is why the modular strategy we are presenting is interesting, in which neither the morphology nor the size of the nanocapsule is modified by adding or removing contrast agents" says Anna Roig.

The study is led by Anna Rosell, Head of the Research Group on Neurovascular Diseases at VHIR, and Anna Roig, Research Professor at ICMAB-CSIC in the Group of Nanoparticles and Nanocomposites. The two researchers participate in the European project MAGBBRIS devoted to "New magnetic biomaterials for brain repair and biomedical imaging after stroke" (coordinated by Rosell). This study, now published in the journal Nanoscale, is part of this project, and is the first step before testing the efficiency of nanocapsules in repair therapies after stroke.

ICMAB and VHIR Communication

Reference Article (Open Access):

PLGA protein nanocarrier with tailor-made fluorescence/MRI/PET imaging modalitiesYajie Zhang, Miguel García-Gabilondo, Alba Grayston, Irene V. J. Feiner, Irene Anton-Sales, Rodrigo A. Loiola, Jordi Llop, Pedro Ramos-Cabrer, Ignasi Barba, David Garcia-Dorado, Fabien Gosselet, Anna Rosell and Anna Roig
Nanoscale, 2020, 12, 4988-5002. DOI: 10.1039/C9NR10620K

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