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Amyloid fibres attract considerable interest due to their biological role in neurodegenerative diseases and their potential as functional biomaterials. Here, we describe an intrinsic signal of amyloid fibres in the near-infrared range. When combined with their recently reported blue luminescence, it paves the way towards new blueprints for the label-free detection of amyloid deposits in in vitro and in vivo contexts. The blue luminescence allows for staining-free characterization of amyloid deposits in human samples. The near-infrared signal offers promising prospects for innovative diagnostic strategies for neurodegenerative diseases—to improve medical care and for the development of new therapies. As a proof of concept, we demonstrate direct detection of amyloid deposits within brains of living, aged mice with Alzheimer’s disease using non-invasive and contrast-agent-free imaging. Ultraviolet–visible–near-infrared optical properties of amyloids open new research avenues for amyloidosis as well as for next-generation biophotonic devices.Two optical signatures of amyloid fibres—luminescence in the blue and a near-infrared signal, which can be observed in in vitro and in vivo tissues—are reported. The findings allow for staining-free characterization of amyloid deposits in human samples and could open the door to innovative diagnostic strategies for neurodegenerative diseases.

Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer. Cellular uptake and phototoxicity of free verteporfin and NLC-verteporfin were studied in vitro in human ovarian cancer cell lines cultured in 2D and 3D-spheroids, and biodistribution and photodynamic therapy were evaluated in vivo in mice. Both molecules were internalized in ovarian cancer cells and strongly inhibited tumor cells viability when exposed to laser light only. In vivo biodistribution and pharmacokinetic studies evidenced a long circulation time of NLC associated with efficient tumor uptake. Administration of 2 mg·kg−1 free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. In contrast, laser light exposure of tumors after intravenous administration of NLC-verteporfin (8 mg·kg−1) significantly inhibited tumor growth without visible toxicity. NLC-verteporfin thus led to efficient verteporfin vectorization to the tumor site and protection from side-effects, providing promising therapeutic prospects for photodynamic therapy of cancer.

Nano‐sized polymer systems are often used as carriers for drugs and contrast agents to increase circulation time and solubility and to reduce possible side effects. These nanomedicines usually accumulate in tumor tissue due to the enhanced permeability and retention (EPR) effect. However, a targeting group may be attached to the polymer carrier in addition to the active substance to further increase tumor accumulation and specificity. In this study, the oligopeptide sequence RGD was chosen to target αvβ3 integrins overexpressed in the tumor vasculature and on some tumor cells. A set of polymer conjugates bearing a fluorescent dye and RGD peptide of different structures (linear, cyclic, branched) was prepared for use in tumor diagnosis, with a potential future application in navigated surgery. The accumulation of the most promising candidate, a targeted fluorescent nanoprobe, increased by 35% in glioblastoma tumors compared to the non‐targeted control, which accumulated only due to the EPR effect. However, the administration of a polymer‐bound modified cilengitide as an antiangiogenic treatment did not show a beneficial effect in the suppression of angiogenesis. Herein, the oligopeptide RGD was chosen to target αvβ3 integrins overexpressed in the tumor vasculature, and fluorescently labeled polymer conjugates with different RGD structures were prepared. The in vitro study reveals the most promising cycloRGD candidate, whose accumulation in glioblastoma was significantly increased compared to the control, for further in vivo investigation as the actively targeted nanoprobe that could meet the requirements of nanoprobe for navigated tumor surgery.

In the human body, copper (Cu) is a major and essential player in a large number of cellular mechanisms and signaling pathways. The involvement of Cu in oxidation–reduction reactions requires close regulation of copper metabolism in order to avoid toxic effects. In many types of cancer, variations in copper protein levels have been demonstrated. These variations result in increased concentrations of intratumoral Cu and alterations in the systemic distribution of copper. Such alterations in Cu homeostasis may promote tumor growth or invasiveness or may even confer resistance to treatments. Once characterized, the dysregulated Cu metabolism is pinpointing several promising biomarkers for clinical use with prognostic or predictive capabilities. The altered Cu metabolism in cancer cells and the different responses of tumor cells to Cu are strongly supporting the development of treatments to disrupt, deplete, or increase Cu levels in tumors. The metallic nature of Cu as a chemical element is key for the development of anticancer agents via the synthesis of nanoparticles or copper-based complexes with antineoplastic properties for therapy. Finally, some of these new therapeutic strategies such as chelators or ionophores have shown promising results in a preclinical setting, and others are already in the clinic.

Peritoneal carcinomatosis occurs frequently in patients with advanced stage gastrointestinal and gynecological cancers. The wide-spread peritoneal micrometastases indicate a poor outlook, as the tumors are difficult to diagnose and challenging to completely eradicate with cytoreductive surgery and chemotherapeutics. Photodynamic diagnosis (PDD) and therapy (PDT), modalities that use photosensitizers for fluorescence detection or photochemical treatment of cancer, are promising theranostic approaches for peritoneal carcinomatosis. This review discusses the leading clinical trials, identifies the major challenges, and presents potential solutions to advance the use of PDD and PDT for the treatment of peritoneal carcinomatosis. While PDD for fluorescence-guided surgery is practically feasible and has achieved clinical success, large randomized trials are required to better evaluate the survival benefits. Although PDT is feasible and combines well with clinically used chemotherapeutics, poor tumor specificity has been associated with severe morbidity. The major challenges for both modalities are to increase the tumor specificity of the photosensitizers, to efficiently treat peritoneal microtumors regardless of their phenotypes, and to improve the ability of the excitation light to reach the cancer tissues. Substantial progress has been achieved in (1) the development of targeted photosensitizers and nanocarriers to improve tumor selectivity, (2) the design of biomodulation strategies to reduce treatment heterogeneity, and (3) the development of novel light application strategies. The use of X-ray-activated PDT during whole abdomen radiotherapy may also be considered to overcome the limited tissue penetration of light. Integrated approaches that take advantage of PDD, cytoreductive surgery, chemotherapies, PDT, and potentially radiotherapy, are likely to achieve the most effective improvement in the management of peritoneal carcinomatosis.

Pancreatic cancer is associated with a poor prognosis despite multimodal treatments. To improve the efficacy of radiotherapy, the use of nanoscintillators is emerging. Made of high‐Z elements, they absorb X‐rays more efficiently than tissues and can locally enhance the radiation dose provided they have accumulated near tumor cells. This study focuses on the role of the coating, a key parameter that controls both in vitro and in vivo properties of nanoparticles, including their internalization, biocompatibility, and therapeutic efficacy. Polyethylene glycol and tripolyphosphate molecules are used to coat lanthanum fluoride nanoscintillators, and their properties are evaluated on pancreatic cancer models. The experiments demonstrate a higher internalization of the nanoparticles when coated with tripolyphosphate, in both 2D and 3D culture models, correlating with greater efficacy under X‐rays, which may be associated with higher radiation dose‐enhancement. The nanoparticles are also injected intravenously in healthy or tumor‐bearing mice in order to study their toxicity, pharmacokinetics, and biodistribution. Despite a strong liver and spleen accumulation, especially for the tripolyphosphate‐coated nanoparticles, no toxicity is observed for either coating. Because they show promising radiation dose‐enhancement in vitro in both culture models and a limited toxicity in vivo, polyethylene glycol‐coated nanoparticles are good candidates for biomedical applications.

Occupational and environmental exposures, particularly those related to urban and suburban atmospheres, are increasingly linked to a range of pulmonary diseases. While diagnostic methods for these diseases are well established, analytical tools for assessing elemental contamination in lung tissue remain underutilized. This study introduces a novel framework based on laser‐induced breakdown spectroscopy (LIBS) for the in situ quantification of elemental titanium (Ti) in lung tissues from both animal models and human specimens. Rigorous validation is conducted using animal models exposed to TiO 2 P25 nanoparticles and a comparative analysis with inductively coupled plasma mass spectrometry. The novel quantitative metric demonstrates robust correlation with elemental concentrations, expanding LIBS utility to volumetric organ analysis. This validated methodology is subsequently applied to human lung specimens preserved in paraffin. The research holds significant promise as a diagnostic tool for assessing exposure levels to environmental or occupational hazards, thereby offering valuable contributions to the fields of toxicology and respiratory medicine.

One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this work, we evaluated the potential of optimized lung MRI techniques and nebulized ultrasmall multimodal gadolinium-based contrast agents [ultrasmall rigid platforms (USRPs)] as a completely noninvasive approach for non-small–cell lung cancer (NSCLC) in vivo detection. A mouse model of NSCLC expressing the luciferase gene was developed. Ultrashort echo-time free-breathing MRI acquisitions were performed before and after i.v. or intrapulmonary administration of the nanoparticles to identify and segment the tumor. After orotracheal or i.v. administration of USRPs, an excellent colocalization of the position the tumor with MRI, bioluminescence and fluorescence reflectance imaging, and histology was observed in all mice. Significantly higher signal enhancements and contrast-to-noise ratios were observed with orotracheal administration using lower doses, reducing the toxicity issues and the interobserver variability in tumor detection. The observations suggested the existence of an unknown original mechanism (different from the enhanced permeability and retention effect) responsible for this phenomenon. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify, and longitudinally monitor the development of submillimetric NSCLCs. The absence of ionizing radiation and high resolution MRI, along with the complete noninvasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge this is the first time that the advantages of an orotracheal administration route are demonstrated for the investigation of the pathomorphological changes due to NSCLCs.

Lung cancer cells resistant to radiotherapy present a significant clinical challenge. Stable telomeric structures, maintained by the TRF2 protein, play a critical role in protecting cells from ionizing radiation. Reduced TRF2 expression increases DNA damage and radiosensitivity. We designed a self‐assembling system utilizing ultra‐small luminescent gold nanoclusters (AuNCs) with radiosensitizing properties, combined with siRNA targeting TRF2. The system forms ≈100  nm non‐spherical structures with AuNCs enriched in the outer layer, exhibiting a 17.6‐fold enhancement in red photoluminescence due to aggregation‐induced effects. This nanoplatform efficiently penetrates lung cancer cells, reducing TRF2 expression by 50%. Under 5 Gy radiotherapy, cells treated with this system show a 1.5‐fold radiosensitivity increase from AuNCs and a 2.3‐fold reduction in clonogenic survival due to telomere deprotection. The AuNC‐siRNATRF2 system combines enhanced optical properties with biological functionality, offering a promising approach to augment radiotherapy efficacy by disrupting telomeric protective mechanisms in cancer cells. Lung cancer cells resistant to radiotherapy pose a challenge, linked to TRF2 protein's role in telomere protection. A self‐assembling system with luminescent gold nanoclusters and siRNA downregulates TRF2, enhancing radiosensitivity. This 100 nm nonspherical structure boosts photoluminescence and penetrates cells, reducing TRF2 expression by 50% and clonogenic survival by 2.3‐fold, promising improved radiotherapy.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, as the most effective chemoradiation therapies achieve unsatisfactory outcomes while associated with high toxicity. Nanoliposomal drug delivery systems are widely used to improve chemotherapy safety, yet passive release of amphiphilic drugs may still associate with adverse toxicity. To address this, we previously developed nanoliposomes functionalized with hydrophobic gold nanoclusters, demonstrating radiocatalytic activity and enhanced chemoradiotherapy effects in 3D PDAC microtumors under synchrotron irradiation. In this study, gold nanocluster‐functionalized nanoliposomes (AuLPs) were optimized and evaluated under 220 kVp orthovoltage X‐ray irradiation, widely used in preclinical irradiation systems. AuLPs containing 0.2 mol% gold nanoclusters produced 1.5‐fold more reactive oxygen species than unloaded liposomes. However, molar ratios above 0.5 mol% and continuous presence of liposomes during irradiation were necessary to improve radiotherapy outcomes in 3D PDAC microtumor models following 4 and 8 Gy irradiation. Pharmacokinetics and biodistribution evaluations showed a modest increase in tumor gold content 24 h post‐injection in orthotopic PDAC models. Altogether, these results underscore the potential of gold‐radiotherapy‐responsive liposomes while highlighting critical formulation challenges, which must be resolved for full therapeutic potential.