Anticancer drug-loaded hydrogels as drug delivery systems for the local treatment of glioblastoma.

Among central nervous system tumors, Glioblastoma (GBM) is the most common, aggressive and neurological destructive primary brain tumor in adults. Standard care therapy for GBM consists in surgical resection of the accessible tumor (without causing neurological damage) followed by chemoradiation. However, several obstacles limit the assessment of tumor response and the delivery of cytotoxic agents at the tumor site, leading to a lack of effectiveness of conventional treatments against GBM and fatal outcome. Despite the efforts of the scientific community to increase the long-term benefits of GBM therapy, at the moment GBM remains incurable. Among the strategies that have been adopted in the last two decades to find new and efficacious therapies for the treatment of GBM, the local delivery of chemotherapeutic drugs in the tumor resection cavity emerged. In this review, our aim is to provide an overview on hydrogels loaded with anticancer drugs for the treatment of GBM recently used in preclinical and clinical studies, their advantages and major limitations for clinical translation. This review is divided in three parts: the first one describes the context of GBM and its current treatments, with a highlight on the role of local delivery in GBM treatment and the development of GBM resection murine models. Then, recent developments in the use of anticancer drug-loaded hydrogels for the treatment of GBM will be detailed. The final section will be focused on the limitations for in vivo studies, clinical translation and the clinical perspectives to the development of hydrogels.

Influence of paramagnetic melanin on the MRI contrast in melanoma: a combined high-field (11.7 T) MRI and EPR study.

Melanoma is the most dangerous form of skin cancer and its incidence is rising each year. Because the current methods of diagnosis based on the visual aspect of the tumor show limitations, several new techniques are emerging to help in this diagnosis, amongst which are magnetic resonance imaging (MRI) and electron paramagnetic resonance (EPR). The origin of the typical contrast pattern observable in melanoma in T1 - and T2 -weighted images remains to be elucidated and is a source of controversy. In addition, melanin could create sufficient magnetic inhomogeneities to allow its visualization on T2 *-weighted images using high-field MRI. In order to elucidate the possible role of melanin in the MRI contrast of melanoma, the present study was designed to correlate the paramagnetic content in melanin pigment to the contrast on T1 -, T2 - and T2 *-weighted images. MR images were obtained in vivo at 11.7 T using four types of experimental tumors with different pigmentations (B16, HBL, LND1 melanomas and KHT sarcomas). The paramagnetic content in melanin pigment was measured by EPR. No significant correlation was observed between the content in melanin and the relaxation times T1 , T2 and T2 *, emphasizing that the presence of pigment alone has negligible effect on the MRI contrast.

Dual anticancer drug/superparamagnetic iron oxide-loaded PLGA-based nanoparticles for cancer therapy and magnetic resonance imaging.

We developed dual paclitaxel (PTX)/superparamagnetic iron oxide (SPIO)-loaded PLGA-based nanoparticles for a theranostic purpose. Nanoparticles presented a spherical morphology and a size of 240 nm. The PTX and iron loading were 1.84 ± 0.4 and 10.4 ± 1.93 mg/100 mg respectively. Relaxometry studies and phantom MRI demonstrated their efficacy as T2 contrast agent. Significant cellular uptake by CT26 cells of nanoparticles was shown by Prussian blue staining and fluorescent microscopy. While SPIO did not show any toxicity in CT-26 cells, PTX-loaded nanoparticles had a cytotoxic activity. PTX-loaded nanoparticle (5 mg/kg) with or without co-encapulated SPIO induced in vivo a regrowth delay of CT26 tumors. Together these multifunctional nanoparticles may be considered as future nanomedicine for simultaneous molecular imaging, drug delivery and real-time monitoring of therapeutic response.

Electron paramagnetic resonance as a sensitive tool to assess the iron oxide content in cells for MRI cell labeling studies.

MRI cell tracking is a promising technique to track various cell types (stem cells, tumor cells, etc.) in living animals. Usually, cells are incubated with iron oxides (T(2) contrast agent) in order to take up the particles before being injected in vivo. Iron oxide quantification is important in such studies for validating the labeling protocols and assessing the dilution of the particles with cell proliferation. We here propose to implement electron paramagnetic resonance (EPR) as a very sensitive method to quantify iron oxide concentration in cells. Iron oxide particles exhibit a unique EPR spectrum, which directly reflects the number of particles in a sample. In order to compare EPR with existing methods (Perls's Prussian blue reaction, ICP-MS and fluorimetry), we labeled tumor cells (melanoma and renal adenocarcinoma cell lines) and fibroblasts with fluorescent iron oxide particles, and determined the limits of detection of the different techniques. We show that EPR is a very sensitive technique and is specific for iron oxide quantification as measurements are not affected by endogenous iron. As a consequence, EPR is well adapted to perform ex vivo analysis of tissues after cell tracking experiments in order to confirm MRI results.