Search Results (7)

A visual Raman nano-delivery system (NS) is a widely used technique for the visualization and diagnosis of tumors and various biological processes. Thiophene-based organic polymers exhibit excellent biocompatibility, making them promising candidates for development as a visual Raman NS. However, materials based on thiophene face limitations due to their absorption spectra not matching with NIR (near-infrared) excitation light, which makes it difficult to achieve enhanced Raman properties and also introduces potential fluorescence interference. In this study, we introduce a donor–acceptor (D-A)-structured thiophene-based polymer, PBDB-T. Due to the D-A molecular modulation, PBDB-T exhibits a narrow bandgap of E_g = 2.63 eV and a red-shifted absorption spectrum, with the absorption edge extending into the NIR region. Upon optimal excitation with 785 nm light, it achieves ultra-strong pre-resonant Raman enhancement while avoiding fluorescence interference. As an intrinsically sensitive visual Raman NS for in vivo imaging, the PBDB-T NS enables the diagnosis of microtumor regions with dimensions of 0.5 mm × 0.9 mm, and also successfully diagnoses deeper tumor tissues, with an in vivo circulation half-life of 14.5 h. This research unveils the potential application of PBDB-T as a NIR excited visual Raman NS for microtumor diagnosis, introducing a new platform for the advancement of “Visualized Drug Delivery Systems”. Moreover, the aforementioned platform enables the development of a more diverse range of targeted visual drug delivery methods, which can be tailored to specific regions. Full article

At this juncture, autofluorescence and narrow-band imaging have resurfaced in the medicine arena in parallel with current technology advancement. The emergence of newly developed optical instrumentation in addition to the discovery of new fluorescence biomolecules have contributed to a refined management of diseases and tumors, especially in the management of upper aerodigestive tract tumors. The advancement in multispectral imaging and micro-endoscopy has also escalated the trends further in the setting of the management of this tumor, in order to gain not only the best treatment outcomes but also facilitate early tumor diagnosis. This includes the usage of autofluorescence endoscopy for screening, diagnosis and treatment of this tumor. This is crucial, as microtumoral deposit at the periphery of the gross tumor can be only assessed via an enhanced endoscopy and even more precisely with autofluorescence endoscopic techniques. Overall, with this new technique, optimum management can be achieved for these patients. Hence, the treatment outcomes can be improved and patients are able to attain better prognosis and survival. Full article

Styrene-co-maleic acid (SMA) copolymer was evaluated as a polymer platform to conjugate with two fluorescent dyes, i.e., 6-aminofluorescein (AF) and Rhodamine (Rho); which spontaneously self-assembles in an aqueous medium and forms a micelle through a non-covalent interaction. These SMA-dye conjugates showed the nanosized micelle formation through dynamic light scattering (DLS) with discrete distributions having mean particle sizes of 135.3 nm, and 190.9 nm for SMA-AF, and SMA-Rho, respectively. The apparent molecular weight of the micelle was evaluated using Sephadex G-100 gel chromatography and it was found that the 49.3 kDa, and 28.7 kDa for SMA-AF, and SMA-Rho, respectively. Moreover, the biodistribution study showed the selective accumulation of the SMA-dye conjugates in the tumor of mice. Taken together, the SMA-dye conjugated micelles appear in high concentrations in the tumor by utilizing the enhanced permeability and retention (EPR) effect of the tumor-targeted delivery. These results indicate that SMA-dye conjugates have the advanced potential as macromolecular fluorescent probes for microtumor imaging by means of a photodynamic diagnosis. Full article

Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers are hydrophobic molecules, nanoliposomes are frequently used to increase the biocompatibility of these therapeutics. However, as nanoliposomes can influence the therapeutic performance of photosensitizers, the most suitable treatment parameters need to be elucidated. Here, we evaluate the efficacy of PDT on spheroid cultures of PANC-1 and MIA PaCa-2 pancreatic cancer cells. Two strategies to photosensitize the pancreatic microtumors were selected, based on either nanoliposomal benzoporphyrin derivative (BPD), or non-liposomal methylene blue (MB). Using a comprehensive image-based assay, our findings show that the PDT efficacy manifests in distinct manners for each photosensitizer. Moreover, the efficacy of each photosensitizer is differentially influenced by the photosensitizer dose, the light dose (radiant exposure or fluence in J/cm²), and the dose rate (fluence rate in mW/cm²). Taken together, our findings illustrate that the most suitable light dosimetry for PDT strongly depends on the selected photosensitization strategy. The PDT dose parameters should therefore always be carefully optimized for different models of cancer. Full article

Hurdles for effective tumor therapy are delayed detection and limited effectiveness of systemic drug therapies by patient-specific multidrug resistance. Non-invasive bioimaging tools such as fluorescence lifetime imaging microscopy (FLIM) and Raman-microspectroscopy have evolved over the last decade, providing the potential to be translated into clinics for early-stage disease detection, in vitro drug screening, and drug efficacy studies in personalized medicine. Accessing tissue- and cell-specific spectral signatures, Raman microspectroscopy has emerged as a diagnostic tool to identify precancerous lesions, cancer stages, or cell malignancy. In vivo Raman measurements have been enabled by recent technological advances in Raman endoscopy and signal-enhancing setups such as coherent anti-stokes Raman spectroscopy or surface-enhanced Raman spectroscopy. FLIM enables in situ investigations of metabolic processes such as glycolysis, oxidative stress, or mitochondrial activity by using the autofluorescence of co-enzymes NADH and FAD, which are associated with intrinsic proteins as a direct measure of tumor metabolism, cell death stages and drug efficacy. The combination of non-invasive and molecular-sensitive in situ techniques and advanced 3D tumor models such as patient-derived organoids or microtumors allows the recapitulation of tumor physiology and metabolism in vitro and facilitates the screening for patient-individualized drug treatment options. Full article

Three-dimensional (3D) culture of tumor spheroids (TSs) within the extracellular matrix (ECM) represents a microtumor model that recapitulates human solid tumors in vivo, and is useful for 3D multiplex phenotypic analysis. However, the low efficiency of 3D culture and limited 3D visualization of microtumor specimens impose technical hurdles for the evaluation of TS-based phenotypic analysis. Here, we report a 3D microtumor culture-to-3D visualization system using a minipillar array chip combined with a tissue optical clearing (TOC) method for high-content phenotypic analysis of microtumors. To prove the utility of this method, phenotypic changes in TSs of human pancreatic cancer cells were determined by co-culture with cancer-associated fibroblasts and M2-type tumor-associated macrophages. Significant improvement was achieved in immunostaining and optical transmission in each TS as well as the entire microtumor specimen, enabling optimization in image-based analysis of the morphology, structural organization, and protein expression in cancer cells and the ECM. Changes in the invasive phenotype, including cellular morphology and expression of epithelial–mesenchymal transition-related proteins and drug-induced apoptosis under stromal cell co-culture were also successfully analyzed. Overall, our study demonstrates that a minipillar array chip combined with TOC offers a novel system for 3D culture-to-3D visualization of microtumors to facilitate high-content phenotypic analysis. Full article

The metabolic plasticity of cancer cells is considered a highly advantageous phenotype that is crucial for disease progression and acquisition of treatment resistance. A better understanding of cancer metabolism and its adaptability after treatments is vital to develop more effective therapies. To screen novel therapies and combination regimens, three-dimensional (3D) culture models of cancers are attractive platforms as they recapitulate key features of cancer. By applying non-perturbative intensity-based redox imaging combined with high-throughput image analysis, we demonstrated metabolic heterogeneity in various 3D culture models of pancreatic cancer. Photodynamic therapy and oxaliplatin chemotherapy, two cancer treatments with relevance to pancreatic cancer, induced perturbations in redox state in 3D microtumor cultures of pancreatic cancer. In an orthotopic mouse model of pancreatic cancer, a similar disruption in redox homeostasis was observed on ex vivo slices following photodynamic therapy in vivo. Taken together, redox imaging on cancer tissues combined with high-throughput analysis can elucidate dynamic spatiotemporal changes in metabolism following treatment, which will benefit the design of new metabolism-targeted therapeutic approaches. Full article