Luminescent organic radical nanoparticles for biomedical applications
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Date
2023-07-10
Authors
Schievano, Giovanni
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Abstract
Cancer represents one of the main health challenges of our times, being a complex pathological condition and leading cause for death in age gap of 60 to 79 (1). In order to face such a challenge, the development of new diagnostic and therapeutic tools is of utmost importance.
Among diagnostic techniques, one of the most versatile is magnetic resonance imaging (MRI) (2–4). At its core MRI is a technique capable of resolving spatially the relaxation times of water magnetic dipoles, as they differ between tissues, obtaining a detailed 3D image of the whole body or one portion of interest. Water relaxation times vary significantly between healthy and damaged or pathogenic tissue, creating a contrast that defines the image (2–4). However, for early-stage detection, small tumours and small lesions, the sensitivity of MRI needs to be increased by the use of contrast agents (5). A contrast agent is a formulation able to modify water relaxation times in its surroundings, therefore creating positive or negative stains in the final image, according to the agent type. Specifically an agent able to prolong longitudinal relaxation is called a T1 agent and appears as a bright spot in the final image (positive contrast), on the other hand a T2 agent affects the orthogonal relaxation appearing in the final image as a dark spot (negative contrast) (3,4,6). Ideally, an MRI contrast agent should be able to accumulate in the pathogenic tissue of choice in order to make it clearly visible to the scan. Up to date, most of MRI contrast agent are water-soluble Gadolinium (III) complexes, that still are among the best performing positive contrast agents, thanks to the very strong intrinsic magnetic field of Gadolinium ions (7,8). However, in recent years, many concerns came up around gadolinium toxicity, in particular its involvement in Nephrogenic Systemic Fibrosis (9,10). Is therefore necessary to develop novel and safer T1 contrast alternatives. Having an intrinsic magnetic field generated by their unpaired electron, stable organic radicals are regarded as promising candidates to substitute Gadolinium (4,11). Since these radicals carry in general a single unpaired electron, the magnetic field associated with them, and consequently their contrast power, is generally much lower than Gd(III) (12) and therefore they require to be formulated in polymeric or dendritic nanostructures to compete with the performances of a single Gadolinium complex (8,11,13). Among various cancer treatments available, hyperthermic therapy (HTT) is one of the most promising new techniques investigated (14–17). Originally intended as an adjuvant therapy, HTT aims to locally increase cells’ temperature up to 47° inducing tissue damages and proteins denaturation (15); such alterations in cell’s integrity induce on one hand apoptosis and necrosis (programmed cell death mechanisms, with associated immune system stimulation), and on the other hand improve other therapies’ efficacy, increasing cancer accessibility to drugs, particles, or radiation (14). Regardless of its promising features, HTT is still limited by the limited tools available: the main challenges associated with it are transferring heat and monitoring the temperature by non-invasive compliant means (15,17). The use of gold and superparamagnetic iron oxide nanoparticles as heating probes is the principal answer to the first challenge (14,17). Temperature measurements required to monitor HTT, need to be highly spatial resolved (up to intracellular cellular level), sensitive and contactless (15,17); in recent years a great development in nanothermometry field has been trying to match these requirements.
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Keywords
Cancer treatment, Nanothermometry