Near-infrared Dye Research Articles

Superhydrophilic Fluorinated Polymer Probe for Zero-Background 19F MRI with Adaptable Targeting Ability.

19F magnetic resonance imaging (19F MRI), with zero background, high tissue penetration depth, excellent spatial resolution, and nonradioactive features, has attracted considerable attention but faces tough challenges due to the shortage of sensitive and selective targetable probes. Herein, we report a biocompatible and highly sensitive 19F MRI probe with an adaptable tumor-targeting ability. The fluorine-grafted polymer (PIBMA-FSON) probes were rich with sulfoxide and carboxy groups, containing a high fluorine content (∼17 wt %). The probes exhibit superhydrophilicity, strong 19F MRI signals (enhancement of ∼95-fold), long transverse relaxation time (T2, 422 ms), and excellent 19F MRI capability. Conjugation using a targeting peptide (Arg-Gly-Asp, RGD) afforded ultrasmall soft polymer probes (PIBMA-FSON-RGD) with superhydrophilicity and tumor-targeting ability suitable for the 19F MRI of orthotopic bladder cancer. Amidification of 5% of the carboxylate units with oleylamine resulted in PIBMAOAm-FSON nanoprobes (NPs) via self-assembly, displaying different targeting toward subcutaneous tumors. Further grafting with near-infrared (NIR) dyes renders the probe suitable for NIR-fluorescence and 19F MRI dual-modality imaging. This study provides a suitable approach for designing highly sensitive and zero-background 19F MRI probes with a tunable tumor-targeting ability.

Production, Characterization, and Application of Hydrophobin-Based IR780 Nanoparticles for Targeted Photothermal Cancer Therapy and Advanced Near-Infrared Imaging.

As a promising approach for breast cancer treatment, photothermal therapy (PTT) features high spatial selectivity, noninvasiveness, and minimal drug resistance. IR780 (a near-infrared fluorescent dye) serves as an effective photosensitizer in PTT cancer therapy. However, the clinical application of IR780 in PTT has been hindered by its poor water solubility and unstable photostability. In this study, a genetically engineered dual-functional fusion protein tLyP-1-MGF6 is successfully constructed and expressed, which presents a novel use of hydrophobin MGF6 for its amphiphilicity combined with the tumor-penetrating peptide tLyP-1 to create an innovative carrier for IR780. These results show this fusion protein serving as a biodegradable and biocompatible carrier, significantly improves the water solubility of IR780 when formulated into nanoparticles. These studies demonstrate that the IR780@tLyP-1-MGF6 nanoparticles significantly enhance tumor targeting and photothermal therapeutic efficacy in comparison with control in vitro and in vivo. These advancements highlight the potential of the unique combination hydrophobin-based IR780 delivery system as a multifunctional nanoplatform for integrated imaging and targeted photothermal treatment of breast cancer.

Recent Advances in NIR-Switchable Multi-Redox Systems Based on Organic Molecules.

In recent years, near-infrared (NIR) dyes, exhibiting absorption in the NIR region (750-2500 nm), have been applied to various optical applications such as security marking, photovoltaic cells and chemotherapy of deep tissues in vivo. Electrochromic systems capable of switching NIR absorption are attractive from the viewpoint of applications for material and life science, and thus several examples have been reported to date. The development of organic-based materials is needed to reduce the environmental impact and improve biocompatibility, however, the switching of NIR absorption based on redox interconversion is still a challenging issue regarding reversibility and durability during interconversion. To overcome this potential instability, several studies on organic electrochromic systems that allow ON/OFF switching of NIR absorption have been developed in recent years. In this review, we focus on redox-active well-defined small molecules that enable ON/OFF switching of NIR absorption, and present recent studies on their intrinsic electrochemical and spectroscopic properties and/or structural characterization of their charged states. We also address more sophisticated electrochromic systems that can modulate their properties in response to external stimuli such as light, heat, and electric potential.

A novel NIR-activatable and photodegradable mitochondria-targeted nano-photosensitizer for superior photodynamic therapy

Photodynamic therapy (PDT) has garnered significant interest as a promising approach for cancer treatment due to its effectiveness, versatility, and non-invasiveness. However, its clinical application is hindered by several factors, such as suboptimal efficacy, poor targeting capabilities, shallow penetration depth, and safety concerns. Herein, we introduce B-SQ, a novel nano-photosensitizer that addresses these challenges. B-SQ is a self-assembling, cancer mitochondria-targeting agent that is both activatable and photodegradable, designed by strategically modifying a near-infrared fluorescent squaraine dye. We extensively assessed the PDT potential of B-SQ in various cancer cell models and explored the molecular mechanisms of PDT-induced cell death. Importantly, B-SQ demonstrated high specificity for cancer cells, and its PDT efficiency was activatable, with near-infrared fluorescence to distinguish cancer cells from normal cells. This work provides the first evidence of B-SQ inducing the intrinsic mitochondrial apoptosis pathway and cell cycle arresting in cancer cells via PDT. Additionally, its photodegradable nature is likely to minimize side effects after treatment. This research introduces an innovative class of nano-photosensitizers that are activatable, targeting cancer mitochondria, and are photodegradable with near-infrared fluorescence. These qualities present new possibilities for safer and more effective clinical cancer treatments in the future.

Synthesis of heavy-atom-free thienoisoindigo dye as near-infrared photosensitizer for type I photodynamic therapy and photoacoustic imaging

Thienoisoindigo (TIIG) has been extensively employed as promising building block of near-infrared (NIR) dyes and organic semiconductor materials. Herein, heavy-atom-free TIIG-based NIR dye TIIGTPA is reported as photosensitizer for combinational photodynamic and photothermal therapy and photoacoustic imaging (PAI). By introducing two methoxy-substituted triphenylamines as the rotors and electron donors at the periphery sites of the electron-deficient TIIG core, dye TIIGTPA featuring Donor-Acceptor-Donor (D-AD) structure is constructed with intensive NIR absorption. Through co-assembly with amphipathic F-127, water-soluble TIIGTPA NPs were prepared with good superoxide anion radical (O2-•) production and high photothermal conversion efficiency (PCE) of 59.0 % under 730 nm photoirradiation. Additionally, the excellent photothermal effect enabled a superior photoacoustic response for tumor blood vessel visualization through PAI. All results indicated the favorable potential of TIIGTPA NPs for PAI-mediated combinational phototherapy.

Synthesis and evaluation of a novel BODIPY fluorescent probe targeting integrin αvβ3 for cancer diagnosis.

A series of integrin αvβ3 targeting BODIPY-RGD conjugate were designed and synthesized. Their in vitro and in vivo fluorescence imaging behaviors were investigated. The small molecule compound was designed as an optical imaging near-infrared fluorescent dye which was combined RGD peptide with the meso-amide BODIPYs using succinic moiety as a spacer. The construction alleviated the traditional BODIPY problems including poor water solubility, aggregate caused quench (ACQ) effect, low biocompatibility, etc. In cellular research, BDP-RGD-2 showed rapid, selective uptake in 3 highly expressing integrin αvβ3 cell lines MDA-MB-231, A549, U87MG at different extent rather than an integrin αvβ3 low level expression cell MCF-7. In animal study, fluorescence imaging of U87MG model targeted by BDP-RGD-2 displayed a highest tumor uptake level and T/N ratio up to 6h after tail-intravenous injection, which demonstrated BDP-RGD-2 was a promising probe for tracing integrin αvβ3 overexpressing tumors.

Computational chemistry facilitates the development of second near-infrared xanthene-based dyes.

The dyes in the second near-infrared (NIR-II) region play a crucial role in advancing imaging technology. However, developing small-molecule dyes in NIR-II poses a significant bottleneck to meet the substantial demands in biological fields, which may be attributed to the lack of a rational design strategy. Herein, we designed a series of rhodamine analogs with more red-shifted emission by replacing the oxygen-bridge atom in xanthene-based dyes with -C(CH3)2, -Si(CH3)2, -SO2, and -P(O)Ph. We investigated the frontier molecular orbital, electrostatic potential surfaces, the interaction region indicator, electron-hole distribution, and absorption and emission spectrum of xanthene-based dyes using (time-dependent) density functional theory. Our results demonstrated that these designed small molecular dyes exhibit long emission wavelengths covering 1377-1809nm. We expected these findings to enable the targeted design of long-wavelength rhodamines. Geometry optimization of dyes in the ground and excited states was carried out at ω-B97XD/Def2SVP level using Gaussian 16 A03. The absorption and emission wavelengths were evaluated using 13 functional, including TPSSH, O3LYP, B3LYP*, B3LYP, PBE0, MPW1B95, PBE-1/3, PBE38, MPWB1K, MN15, BHandHLYP, ω-B97XD, and CAM-B3LYP.

Evaluation of a targeted anti-αvβ3 integrin near-infrared fluorescent dye for fluorescence-guided resection of naturally occurring soft tissue sarcomas in dogs.

Complete resection is a key prognostic factor for survival in patients with soft tissue sarcoma (STS), in humas and companion animals alike. Fluorescence-guided surgery could improve resection accuracy. As dogs are frequently affected by STS, they serve as a model to test an anti-αvβ3 integrin targeting near-infrared fluorescent (NIRF) dye (AngiostampTM800) for fluorescence-guided surgery in STS to evaluate its safety and feasibility in dogs, and if it translates into a clinically relevant benefit compared to the standard of care with regards to completeness of surgery and local recurrence. Furthermore, we aimed to correlate target expression and NIRF-signal intensity. Twenty dogs with STS were randomly allocated to either receive Angiostamp™ (NIRF group) or physiologic saline (control group) preoperatively. The researchers were blinded for treatment, and resections were adapted based on the NIRF-signal, if needed. Margin status was histologically determined at the 1 and 3cm margin. The tumor-to-background ratio was measured in native tissue biopsies and formalin-fixed tissue. The fluorescent area was compared to the corresponding tumor areas as confirmed by histology using the Dice coefficient. Target expression was quantified by immunohistochemistry and correlated to NIRF-signal ratios. A fluorescent signal was detected in all 10 tumors of the NIRF group, with a tumor-to-background ratioof 7.4 ± 5.8 in native biopsies and 13.5 ± 10.9 in formalin-fixed tissue. In the NIRF group, resection margins were adapted in 5/10 cases, leading to complete resection and preventing R1 in four of these cases. In the NIRF and control group 9/10 and 8/10 resections were R0, with one local recurrence in each group and one sarcoma-related death in the NIRF group. The NIRF-signal correlated with the histologically confirmed tumor area (Dice coefficient 0.75 ± 0.17). Target expression was higher in tumor compared to peritumoral tissue (p < 0.0003) and showed a moderate correlation with the NIRF-signal (r = 0.6516, p < 0.0001). Fluorescence-guided surgery using Angiostamp™ can pinpoint residual disease in the tumor bed and contributes to an improved resection accuracy in canine STS.

Structural Engineering of Cationic Block Copolymer Architectures for Selective Breaching of Prokaryotic and Eukaryotic Biological Species.

Positively charged antimicrobial polymers are known to cause severe damage to biological systems, and thus synthetic strategies are urgently required to design next-generation nontoxic cationic macromolecular architectures for healthcare applications. Here, we report a structural-engineering strategy to build cationic linear and star-block copolymer nanoarchitectures having identical chemical composition, molar mass, nanoparticle size, and positive surface charge, yet they differ distinctly in their biological action in breaching prokaryotic species such as E. coli (Gram-negative bacteria) without affecting eukaryotic species like red-blood and mammalian cells. For this purpose, linear and star-block structures are built on a polycaprolactone biodegradable platform having an imidazolium positive handle. Under physiological conditions, the linear architecture exhibits toxicity indiscriminately to all biological species, whereas its star counterpart is remarkably selective in membrane breaching action toward bacteria while maintaining inertness toward eukaryotic species. Confocal microscopy analysis of HPTS fluorescent dye-loaded star-polymer nanoparticles substantiated their antimicrobial action in E. coli. Tissue-penetrable near-infrared fluorescent dye (IR-780) loaded NP aided the in vivo biodistribution analysis and ex vivo quantification of cationic species' accumulations in vital organs in mice. Azithromycin, a clinical water-insoluble macrolide, is delivered from the star platform to accomplish synergistic antimicrobial activity by the combination of bactericidal-bacteriostatic action of the polymer carrier and drug together in a single system.

Fused Hexabenzocoronene-Porphyrin Conjugates with Tailorable Excited-State Lifetimes.

A new clear-cut strategy for fusing N-heterocyclic and carbon-pure systems is introduced en route to a versatile platform of multi-purpose tetrapyrrolic chromophores. In particular, three novel C-C bond-fused porphyrin-hexabenzocoronene (HBC) conjugates were synthesized under oxidative cyclodehydrogenation conditions, starting from tailor-made nickel porphyrin precursors. The fusion of the individual aromatic systems via 5-membered rings led to highly soluble π-extended porphyrins in excellent yields. The resulting porphyrin-HBC conjugates exhibit absorption cross-sections that are of interdisciplinary interest in the ever-growing field of organic photovoltaics and near-infrared (NIR) dyes. Quantum chemical calculations show that the newly formed 5-membered rings induce biradicaloid character in the porphyrin core, which has a strong impact on excited state lifetimes. This is confirmed by a thorough optoelectronic and time-resolved characterization in order to understand these unique features better. Broadened absorption characteristics go hand-in-hand with short-lived excited states with up to six orders of magnitude faster decay rates.

Pre-clinical study of IR808 dye for cervical cancer in vitro and in vivo imaging.

There is an urgent need for improved methods for early screening and rapid diagnosis of cervical cancer since current conventional screening methods are plagued by operator subjectivity and unnecessary biopsies. IR808 is a tumour-targeting near-infrared (NIR) fluorescent dye that permits NIR imaging without the requirement of chemical conjugation. Our study investigates an IR808-based strategy for real-time monitoring of the cervix in vivo and rapid assessment of cervical specimens in vitro. We investigated the uptake of IR808 in vitro using normal cervical epithelial cells and three cervical cancer cell lines. The biodistribution of IR808 was examined in vivo via intravenous injection into tumour-bearing mice. Additionally, in vitro tissues were stained with IR808 to simulate the identification of cervical tumors in the clinical setting. Biocompatibility of the dye in both cellular and animal models was also examined. IR808 exhibited significant tumour-to-background ratios in fluorescence molecular imaging of in vivo tumors in nude mice. The application of NIR fluorescent dye IR808 in specific imaging screening, safe and non-invasive real-time monitoring, and rapid identification of cervical tumors from tissue specimens is expected to improve current screening methods for cervical cancer.

MnO2 nanozyme boosts synergistic photodynamic/photothermal therapy of bacterial biofilm infections

As a near-infrared (NIR) adsorbing dye approved by the FDA, indocyanine green (ICG) can serve as an attractive therapeutic agent to combat biofilm infections through synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) due to its deep-tissue penetration ability. However, ICG usually suffers from photo/thermal instability. Herein, to tackle the issues, bovine serum albumin (BSA) stabilized nanozyme MnO2 (BSA/MnO2) was synthesized by reducing manganese permanganate (KMnO4) with BSA, which was further loaded with ICG and coated with the positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC) as the bacterial targeting moiety through noncovalent interactions. The constructed ICG@BSA/MnO2@HACC (IBMH) displays good photodynamic/thermal effects and bacterial targetability, enabling a synergistic PDT/PTT therapy against biofilm-associated infections. Compared with free ICG, IBMH exhibits enhanced photo/thermal stability owing to the O2-generating and photothermal capacities of MnO2, which significantly promotes biofilm phototherapy. Meanwhile, IBMH can effectively achieve anti-inflammatory effect due to the reactive oxygen species (ROS) scavenging capacity of nanozyme MnO2, thereby greatly accelerating wound healing after synergistic PDT/PTT. Both in vitro and in vivo assays solidly demonstrate its satisfactory anti-biofilm and anti-inflammatory effects. Therefore, our research proposes a promising and convenient strategy for developing multifunctional nanozyme for synergistic PDT/PTT of biofilm infection.

Micelle-encapsulated IR783 for enhanced photothermal therapy in mouse breast cancer

BackgroundPhotothermal therapy, an emerging cancer treatment, selectively eliminates lesions using photothermal compounds that convert light into heat. IR783, a near-infrared fluorescent heptamethine cyanine dye, has been used to achieve selective hyperthermic effects in target tissues via near-infrared irradiation. To implement IR783 as a photothermal agent, IR783 biodistribution must be calibrated to achieve a constant and uniform concentration in target cells. Accordingly, we developed micelle-encapsulated IR783 (IR783 micelles) and evaluated their effectiveness as photothermal drugs. MethodsIn vitro, the photothermic effects of free IR783 and IR783 micelle solutions induced by near-infrared light irradiation were analyzed. Additionally, we investigated the mechanism of cell death mediated by photothermal therapy using free IR783 and IR783 micelles in mouse breast cancer (EMT6) cells. In vivo, the efficacy of photothermal therapy with both free IR783 and IR783 micelles was examined in EMT6-bearing mice. ResultsIn vitro, the temperature of free and micelle-encapsulated IR783 solutions increased after near-infrared irradiation. Near-infrared irradiation with free IR783 and IR783 micelles induced cytotoxicity in cancer cells by generating heat. In vivo, IR783 micelles elicited more preferential tumor tissue uptake and enhanced the antitumor effects of photothermal therapy at a lower light dose relative to free IR783. ConclusionsOverall, these results suggest that IR783 micelles could accumulate in mouse breast cancer tissues and exhibit enhanced antitumor effects when used as a photothermal therapy, with superior effects obtained at 2.1 W/cm2 (252 J/cm2) compared with that of free IR783.

Stabilizing Dye-Sensitized Upconversion Hybrids by Cyclooctatetraene.

Lanthanide-doped upconversion nanoparticles (UCNPs) can convert low-energy near-infrared (NIR) light into high-energy visible light, making them valuable for broad applications. UCNPs often suffer from poor light-harvesting capabilities, which can be significantly improved by incorporating organic dye antennas. However, the dye-sensitized upconversion systems are prone to severe photobleaching in an ambient atmosphere. Here, we present a synergistic approach to mitigate photobleaching by introducing triplet state quencher cyclooctatetraene (COT). COT effectively suppresses the generation of singlet oxygen by quenching the triplet states of the dye and consumes the existing singlet oxygen through oxidant reactions. The inclusion of COT extends the half-life of IR806 by 4.7-times by preventing the oxidation of its poly(methylene) chains. Without significantly affecting emission intensity and dynamics, COT effectively stabilized dye-UCNPs, demonstrating a notable 3.9-fold increase in half-life under continuous laser irradiation. Our findings suggest a new strategy to enhance the photostability of near-infrared dyes and dye-sensitized upconversion nanohybrids.

Incorporation of pre- and intra-operative sentinel lymph node mapping techniques in dogs with apocrine gland anal sac adenocarcinoma

The high incidence of nodal metastasis, variable lymphatic drainage patterns, and prognostic significance of nodal metastasis in dogs with apocrine gland anal sac adenocarcinoma (AGASACA) highlight the need for development of standardized techniques for lymph node staging in canine AGASACA. The aim of this study was to develop and describe the utility of pre- and intra-operative sentinel lymph node (SLN) mapping techniques for subsequent nodal extirpation and histologic assessment in dogs with AGASACA. A prospective clinical trial was performed as a pilot study. Eight client-owned dogs with unilateral AGASACA were enrolled. Preoperative contrast-enhanced ultrasound (CEUS) via transrectal ultrasound (TRUS) and CT-lymphography (CTL) was followed by intraoperative SLN mapping within 7 days utilizing a visible dye (methylene blue [MB]) and a near-infrared (NIR) fluorescent dye (indocyanine green [ICG]) with subsequent nodal extirpation and routine anal sacculectomy. In all dogs, preoperative CTL and intraoperative SLN mapping identified at least one SLN. Pre- and intra-operative findings differed in 4/8 dogs. Preoperative CEUS identified a SLN in 7/8 dogs, but the exact location of the SLN was indeterminate. Extirpated lymph nodes were metastatic in 2/8 dogs. Preoperative CTL and intraoperative MB and ICG were an effective combination of SLN mapping techniques in dogs with AGASACA. These techniques each provided unique advantages. Combined, they identified and guided extirpation of early metastatic lymph nodes. Large-scale, prospective studies utilizing the techniques described are needed to accurately determine the incidence and significance of early/occult nodal metastasis in canine AGASACA.

Tannic Acid-Based Self-Assembling Nanocarriers with Antiphotobleaching and Controlled Releasing Properties for Collaborative Near-Infrared Photothermal/Photodynamic Therapy.

Near-infrared (NIR) organic materials have been widely developed for tumor phototherapy due to their deep tumor penetration, good biodegradability, and high photothermal conversion (PCE). However, most of the NIR organic dyes are easily destroyed by photooxidation due to their big and long conjugated structures, such as cyanine dyes. Under light irradiation, the reactive oxygen species (ROS) produced by these NIR dyes can easily break their conjugated skeleton, resulting in a dramatic decrease in phototherapeutic efficiency. Herein, an NIR organic dye cyanine dye (CyS) and a photosensitizer methylene blue (MB) were chosen to prepare nanocarrier CMTNPs by facile self-assembling with a natural antioxidant, tannic acid (TA). TA can greatly enhance the stability of NIR cyanine dyes by scavenging ROS. Furthermore, CMTNPs have a character of pH/thermal dual response, allowing for controlled release of MB in the slightly acidic tumor environment during photothermal therapy. The released MB can turn on both fluorescence and photodynamic therapy effects. In vitro and in vivo experiments demonstrated the remarkable tumor ablation ability of CMTNPs. Thus, our study provided an antiphotobleaching and controlled release photosensitizer strategy through the introduction of antioxidant TA into the nanocarrier for efficient collaborative photothermal/photodynamic therapy.

Collagen-targeted protein nanomicelles for the imaging of non-alcoholic steatohepatitis

In vivo molecular imaging tools hold immense potential to drive transformative breakthroughs by enabling researchers to visualize cellular and molecular interactions in real-time and/or at high resolution. These advancements will facilitate a deeper understanding of fundamental biological processes and their dysregulation in disease states. Here, we develop and characterize a self-assembling protein nanomicelle called collagen type I binding – thermoresponsive assembled protein (Col1-TRAP) that binds tightly to type I collagen in vitro with nanomolar affinity. For ex vivo visualization, Col1-TRAP is labeled with a near-infrared fluorescent dye (NIR-Col1-TRAP). Both Col1-TRAP and NIR-Col1-TRAP display approximately a 3.8-fold greater binding to type I collagen compared to TRAP when measured by surface plasmon resonance (SPR). We present a proof-of-concept study using NIR-Col1-TRAP to detect fibrotic type I collagen deposition ex vivo in the livers of mice with non-alcoholic steatohepatitis (NASH). We show that NIR-Col1-TRAP demonstrates significantly decreased plasma recirculation time as well as increased liver accumulation in the NASH mice compared to mice without disease over 4 hours. As a result, NIR-Col1-TRAP shows potential as an imaging probe for NASH with in vivo targeting performance after injection in mice. Statement of significanceDirect molecular imaging of fibrosis in NASH patients enables the diagnosis and monitoring of disease progression with greater specificity and resolution than do elastography-based methods or blood tests. In addition, protein-based imaging probes are more advantageous than alternatives due to their biodegradability and scalable biosynthesis. With the aid of computational modeling, we have designed a self-assembled protein micelle that binds to fibrillar and monomeric collagen in vitro. After the protein was labeled with near-infrared fluorescent dye, we injected the compound into mice fed on a NASH diet. NIR-Col1-TRAP clears from the serum faster in these mice compared to control mice, and accumulates significantly more in fibrotic livers.This work advances the development of targeted protein probes for in vivo fibrosis imaging.

Study protocol for Near-infrared molecular imaging for lung cancer detection and treatment during mini-invasive surgery (phase II Trial) - (the RECOGNISE study)

Introduction. To date, radical surgery remains the best curative option in patients with early-stage lung cancer. In patients with small lung lesions, video-assisted thoracic surgery (VATS) should be increasingly chosen as a fundamental alternative to thoracotomy as it is associated with less postoperative pain and better quality of life. This scenario necessarily increases the need for thoracic surgeons to implement new localization techniques. The conventional near-infrared (NIR) indocyanine green (ICG) method demonstrated a significant limitation in deep cancer recognition, principally due to its intrinsic low-depth tissue penetration. Similarly, the lymph-node sentinel approach conducted by the ICG method was demonstrated to be inefficient, mainly due to the non-specificity of the tracker and the irregular pathway of pulmonary lymph node drainage. Our study aims to evaluate the effectiveness of Cetuximab- IRDye800CW in marking lung nodules and mediastinal lymph nodes. Methods and analysis. This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and lymph-node metastases in patients with lung cancer who are undergoing video-assisted thoracic surgery (VATS). Cetuximab is a monoclonal antibody that binds, inhibits, and degrade the EGFR. The IRDye® 800CW, an indocyanine-type NIR fluorophore, demonstrated enhanced tissue penetration compared to other NIR dyes. The combination with the clinical approved monoclonal antibody anti-epidermal growth factor EGFR Cetuximab (Cetuximab-IRDye800) has shown promising results as a specific tracker in different cancer types (i.e., brain, pancreas, head, and neck). The study’s primary outcome is focused on the proportion of patients with lung nodules detected during surgery using an NIR camera. The secondary outcomes include a broad spectrum of items, including the proportion of patients with detection of unexpected cancer localization during surgery by NIR camera and the proportion of patients with negative surgical margins, the evaluation of the time spawns between the insertion of the NIR camera and the visualization of the nodule and the possible morbidity of the drug assessed during and after the drug infusion. Ethics and dissemination. This trial has been approved by the Ethical Committee of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino (Torino, Italy) and by the Italian Medicines Agency (AIFA). Findings will be written as methodology papers for conference presentations and published in peer-reviewed journals. The Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, the University of Torino, and the AIRC Public Engagement Divisions will help identify how best to publicize the findings.Trial registration EudraCT 202,100,645,430. ClinicalTrials.gov NCT06101394 (October 23, 2023).

Oxidation of Weakly Interacting Diradicals: An Approach for Strong and Tunable Near-Infrared-Absorbing Dyes Based on Small Chromophores.

Near-infrared (NIR)-absorbing dyes are valuable for various applications, such as bioimaging and electronic devices. This work introduces a novel approach for designing NIR dyes, oxidation of weakly coupled diradicals. Our approach features a weak exchange interaction in diradicals, which potentially leads to bonding/antibonding molecular orbitals with a small energy gap. We found that removing one of two singly occupied molecular orbital electrons of the diradicals results in an exceptionally narrow frontier orbital energy gap. We examined a series of Blatter radical dimers, and the most weakly coupled diradical prepared in this work (ΔEST ∼ 0.12 eV) with a molecular weight of 590 Da exhibited a strong NIR absorption band reaching 2200 nm upon one-electron oxidation. The optical band gaps of the radical cations strongly correlate to the exchange interaction in the precursor neutral species, offering prediction and fine-tuning of the optical band gap in the NIR region.

Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases.

Metastatic breast cancer is a devastating disease with very limited therapeutic options, calling for new therapeutic strategies. Oncogenic miRNAs have been shown to be associated with the metastatic potential of breast cancer and are implicated in tumor cell migration, invasion, and viability. However, it can be difficult to deliver an inhibitory RNA molecule to the tissue of interest. To overcome this challenge and deliver active antisense oligonucleotides to tumors, we utilized magnetic iron oxide nanoparticles as a delivery platform. These nanoparticles target tissues with increased vascular permeability, such as sites of inflammation or cancer. Delivery of these nanoparticles can be monitored in vivo by magnetic resonance imaging (MRI) due to their magnetic properties. Translation of this therapeutic approach into the clinic will be more accessible because of its compatibility with this relevant imaging modality. They can also be labeled with other imaging reporters such as a Cy5.5 near-infrared optical dye for correlative optical imaging and fluorescence microscopy. Here, we demonstrate that nanoparticles labeled with Cy5.5 and conjugated to therapeutic oligomers targeting oncogenic miRNA-10b (termed MN-anti-miR10b, or "nanodrug") administered intravenously accumulate in metastatic sites, opening a possibility for therapeutic intervention of metastatic breast cancer.