Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice.

Background: Glioblastoma (GB), the most aggressive brain cancer, remains a critical clinical challenge due to its resistance to conventional treatments. Here, we introduce a locoregional targeted-α-therapy (TAT) with the rat monoclonal antibody 9E7.4 targeting murine syndecan-1 (SDC1) coupled to the α-emitter radionuclide astatine-211 (At-9E7.

Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: Between chemoattraction and tumor shaping into resection cavities.

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells.

Rapamycin-Loaded Lipid Nanocapsules Induce Selective Inhibition of the mTORC1-Signaling Pathway in Glioblastoma Cells.

Inhibition of the PI3K/Akt/mTOR signaling pathway represents a potential issue for the treatment of cancer, including glioblastoma. As such, rapamycin that inhibits the mechanistic target of rapamycin (mTOR), the downstream effector of this signaling pathway, is of great interest. However, clinical development of rapamycin has floundered due to the lack of a suitable formulation of delivery systems.

Targeting Tumor Associated Macrophages to Overcome Conventional Treatment Resistance in Glioblastoma.

Glioblastoma (GB) is the most common and devastating form of brain cancer. Despite conventional treatments, progression or recurrences are systematic. In recent years, immunotherapies have emerged as an effective treatment in a number of cancers, leaving the question of their usefulness also faced with the particular case of brain tumors.

Potential for Nuclear Medicine Therapy for Glioblastoma Treatment.

Glioblastoma is the most common malignant adult brain tumor and has a very poor patient prognosis. The mean survival for highly proliferative glioblastoma is only 10 to 14 months despite an aggressive current therapeutic approach known as Stupp's protocol, which consists of debulking surgery followed by radiotherapy and chemotherapy. Despite several clinical trials using anti-angiogenic targeted therapies, glioblastoma medical care remains without major progress in the last decade.

Rhenium-188 Labeled Radiopharmaceuticals: Current Clinical Applications in Oncology and Promising Perspectives.

Rhenium-188 (Re) is a high energy beta-emitting radioisotope with a short 16.9 h physical half-life, which has been shown to be a very attractive candidate for use in therapeutic nuclear medicine. The high beta emission has an average energy of 784 keV and a maximum energy of 2.

Hybrid Gd/cisplatin cross-linked polymer nanoparticles enhance platinum accumulation and formation of DNA adducts in glioblastoma cell lines.

Glioblastoma is the most frequent and aggressive primary malignant tumor of the central nervous system with a gloomy prognosis. Platinum derivatives and one among them, cisplatin, exhibited promising results when locally administered into the brain of glioblastoma bearing rats. Nanovectorization of anticancer agents through polymeric nanoparticles may even promote drug accumulation within cells, thus concentrating the drug efficiently at its target.

Locoregional Confinement and Major Clinical Benefit of Re-Loaded CXCR4-Targeted Nanocarriers in an Orthotopic Human to Mouse Model of Glioblastoma.

Purpose: Gold standard beam radiation for glioblastoma (GBM) treatment is challenged by resistance phenomena occurring in cellular populations well prepared to survive or to repair damage caused by radiation. Among signals that have been linked with radio-resistance, the SDF1/CXCR4 axis, associated with cancer stem-like cell, may be an opportune target. To avoid the problem of systemic toxicity and blood-brain barrier crossing, the relevance and efficacy of an original system of local brain internal radiation therapy combining a radiopharmaceutical with an immuno-nanoparticle was investigated.

Characterization of the distribution, retention, and efficacy of internal radiation of Re-lipid nanocapsules in an immunocompromised human glioblastoma model.

Internal radiation strategies hold great promise for glioblastoma (GB) therapy. We previously developed a nanovectorized radiotherapy that consists of lipid nanocapsules loaded with a lipophilic complex of Rhenium-188 (LNCRe-SSS). This approach resulted in an 83 % cure rate in the 9L rat glioma model, showing great promise.

68Ga and 188Re Starch-Based Microparticles as Theranostic Tool for the Hepatocellular Carcinoma: Radiolabeling and Preliminary In Vivo Rat Studies.

Purpose: This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain a unique theranostic vector for the treatment of Hepatocellular Carcinoma.

Methods: Optimal labeling conditions and composition of freeze-dried kits were defined by monitoring the radiochemical purity while varying several parameters. In vitro stability studies were carried out, as well as an in vivo biodistribution as a preliminary approach with the intra-arterial injection of 68Ga radiolabeled SBMP into the hepatic artery of DENA-induced rats followed by PET/CT imaging.

Dendrimers as Innovative Radiopharmaceuticals in Cancer Radionanotherapy.

Radiotherapy is one of the most commonly used cancer treatments, with an estimate of 40% success that could be improved further if more efficient targeting and retention of radiation at the tumor site were achieved. This review focuses on the use of dendrimers in radionanotherapy, an emerging technology aimed to improve the efficiency of radiotherapy by implementing nanovectorization, an already established praxis in drug delivery and diagnosis. The labeling of dendrimers with radionuclides also aims to reduce the dose of radiolabeled materials and, hence, their toxicity and tumor resistance.

Nanomedicine to overcome radioresistance in glioblastoma stem-like cells and surviving clones.

Radiotherapy is one of the standard treatments for glioblastoma, but its effectiveness often encounters the phenomenon of radioresistance. This resistance was recently attributed to distinct cell contingents known as glioblastoma stem-like cells (GSCs) and dominant clones. It is characterized in particular by the activation of signaling pathways and DNA repair mechanisms.

Tumour targeting of lipid nanocapsules grafted with cRGD peptides.

Combining targeting to therapy remains a major challenge in cancer treatment. To address this subject, the surface of lipid nanocapsules (LNC) was modified by grafting cRGD peptides, which are known to be recognised by αvβ3 integrins expressed by tumour endothelium and cancer cells. Applicability of this LNC-cRGD in tumour targeting was first assessed in vitro by the use of U87MG glioma cells.

Lysozyme encapsulation into nanostructured CaCO microparticles using a supercritical CO process and comparison with the normal route.

The aim of the present work was to assess the merits of supercritical CO (SC-CO) as a process for protein encapsulation into calcium carbonate microparticles. Lysozyme, chosen as a model protein, was entrapped during CaCO precipitation in two different media: water (normal route) and SC-CO. The particles were characterized and compared in terms of size, zeta potential, morphology by SEM, crystal polymorph and lysozyme encapsulation.

Effect of particle size on the biodistribution of lipid nanocapsules: comparison between nuclear and fluorescence imaging and counting.

In vivo biodistribution of nanoparticles depends on several physicochemical parameters such as size. After intravenous injection of 25, 50 and 100 nm lipid nanocapsules (LNC) in nude mice bearing HEK293(β3) tumour xenografts, biodistribution was evaluated by γ-scintigraphy and by γ-counting. The small LNC 25 nm disappeared faster than the larger LNC 50 and 100 nm from the blood circulation due to faster elimination and wider tissue distribution.

Nanovectorized radiotherapy: a new strategy to induce anti-tumor immunity.

Recent experimental findings show that activation of the host immune system is required for the success of chemo- and radiotherapy. However, clinically apparent tumors have already developed multiple mechanisms to escape anti-tumor immunity. The fact that tumors are able to induce a state of tolerance and immunosuppression is a major obstacle in immunotherapy.

Tumor eradication in rat glioma and bypass of immunosuppressive barriers using internal radiation with (188)Re-lipid nanocapsules.

To date, glioblastoma treatments have only been palliative. In this context, locoregional drug delivery strategies, which allow for blood--brain barrier bypass and reduced systemic toxicity, are of major significance. Recent progress in nanotechnology has led to the development of colloidal carriers of radiopharmaceutics, such as lipid nanocapsules loaded with rhenium-188 (LNC(188)Re-SSS) that are implanted in the brain.

Development and characterization of immuno-nanocarriers targeting the cancer stem cell marker AC133.

In the context of targeted therapy, we addressed the possibility of developing a drug delivery nanocarrier capable to specifically reach cancer cells that express the most prominent marker associated with cancer stem cell (CSC) phenotype, AC133. For this purpose, 100nm lipid nanocapsules (LNCs) were functionalized with a monoclonal antibody (mAb) directed against AC133 according to two distinct methods: firstly, post-insertion within 100nm LNCs of a lipid poly(ethylene glycol) functionalized with reactive-sulfhydryl maleimide groups (DSPE-PEG(2000)-maleimide) followed by thiolated mAb coupling, and, secondly, creation of a thiolated lipo-immunoglobulin between DSPE-PEG(2000)-maleimide and AC133, then post-inserted within LNCs. Due to the reduced number of purification steps, lower amounts of DSPE-PEG(2000)-maleimide that were necessary as well as lower number of free maleimide functions present onto the surface of immuno-LNC, the second method was found to be more appropriate.

Lipid nanocapsules loaded with rhenium-188 reduce tumor progression in a rat hepatocellular carcinoma model.

Background: Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC(188)Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model.

Methodology/principal Findings: Animals were treated with an injection of LNC(188)Re-SSS (80 MBq or 120 MBq).

The importance of endo-lysosomal escape with lipid nanocapsules for drug subcellular bioavailability.

To establish the therapeutic relevance of new nanocarriers, rationalization of knowledge on their interactions with biological structures is essential. In the present study, we have investigated endocytosis and intracellular trafficking of lipid nanocapsules (LNCs) in rat glioma cells. Radiolabelled and fluorescent LNCs were synthesized by using a phase inversion process that follows the formation of an oil/water microemulsion containing triglycerides, lecithins and a non-ionic surfactant, the hydroxystearate of poly(ethylene glycol) (HS-PEG).

New starch-based radiotracer for lung perfusion scintigraphy.

Purpose: In order to avoid the microbiological risks linked to human serum albumin macroaggregates (MAA) used for lung perfusion scintigraphy, we developed a new starch-based Tc-99m potential radiopharmaceutical.

Methods: Microparticles were prepared from oxidised starch coupled to natural polyamine for Tc-99m complexation. Suspensions were formulated as ready-to-use kits for easy one-step labelling procedures.

Self-assembled monolayers of bisphosphonates: influence of side chain steric hindrance.

Bisphosphonates form self-assembled monolayers (SAMs) spontaneously on stainless steel, silicon, and titanium oxidized surfaces. We used contact angle measurements, atomic force microscopy, and X-ray reflectivity analysis to study the formation of SAMs on a model surface of ultraflat titanium (rms = 0.2 nm).