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Photothermal therapy (PTT) is a method for eradicating tumor tissues through the use of photothermal materials and photosensitizing agents that absorb light energy from laser sources and convert it into heat, which selectively targets and destroys cancer cells while sparing healthy tissue. MXenes have been intensively investigated as photosensitizing agents for PTT. However, achieving the selectivity of MXenes to the tumor cells remains a challenge. Specific antibodies (Ab) against tumor antigens can achieve homing of the photosensitizing agents toward tumor cells, but their immobilization on MXene received little attention. Here, we offer a strategy for the selective ablation of melanoma cells using MXene-polydopamine-antiCEACAM1 Ab complexes. We coated Ti3C2Tx MXene with polydopamine (PDA), a natural compound that attaches Ab to the MXene surface, followed by conjugation with an anti-CEACAM1 Ab. Our experiments confirm the biocompatibility of the Ti3C2Tx-PDA and Ti3C2Tx-PDA-antiCEACAM1 Ab complexes across various cell types. We also established a protocol for the selective ablation of CEACAM1-positive melanoma cells using near-infrared irradiation. The obtained complexes exhibit high selectivity and efficiency in targeting and eliminating CEACAM1-positive melanoma cells while sparing CEACAM1-negative cells. These results demonstrate the potential of MXene-PDA-Ab complexes for cancer therapy. They underline the critical role of targeted therapies in oncology, offering a promising avenue for the precise and safe treatment of melanoma and possibly other cancers characterized by specific biomarkers. Future research will aim to refine these complexes for clinical use, paving the way for new strategies for cancer treatment.
Assuntos
Indóis , Melanoma , Polímeros , Polímeros/química , Indóis/química , Indóis/farmacologia , Humanos , Melanoma/patologia , Melanoma/tratamento farmacológico , Melanoma/terapia , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Titânio/química , Animais , Camundongos , Antígeno Carcinoembrionário/imunologia , Terapia FototérmicaRESUMO
Introduction: Patients with lung cancer receive treatment according to National Cancer Comprehensive Network (NCCN) standards. However, disease recurrence is reported in about 30% of patients during the first five years. Our study aimed to establish independent predictors of lung cancer recurrence. Material and methods: 104 patients with definitive treatment for non-small-cell lung carcinoma receiving standard adjuvant chemotherapy in the period 2014-2018 in our cancer center were retrospectively reviewed. The prognostic significance of five routine immunohistochemical (IHC) markers was examined. Results: During the follow-up period disease recurrence occurred in 42 (40.4%) of the 104 enrolled patients. The median recurrence-free survival was 56.3 months, range 4-84.0 months (95% CI = 46.866-65.683). The recurrence-free survival rate was 58.8%. The frequencies of locoregional recurrence, lung recurrence, kidney, bone, lymph nodes of the neck, liver, and brain recurrence were 23.8%, 21.5%, 16.7%, 9.5%, 9.5%, 9.5% and 9.5%, respectively. Conclusions: Using the Cox regression model, category T, histological differentiation, and smoking status were identified as independent predictors of disease recurrence. The studied biological markers (PD-L1, Ki67, p53, epidermal growth factor receptor, and ALK) did not help the model predict disease recurrence. For statistical reliability, it is necessary to conduct a study on a larger cohort of patients and compare the mutual influence of several biomarkers.
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The application of chitosan (Ch) as a promising biopolymer with hemostatic properties and high biocompatibility is limited due to its prolonged degradation time, which, in turn, slows the repair process. In the present research, we aimed to develop new technologies to reduce the biodegradation time of Ch-based materials for hemostatic application. This study was undertaken to assess the biocompatibility and hemostatic and tissue-regeneration performance of Ch-PEO-copolymer prepared by electrospinning technique. Chitosan electrospinning membranes (ChEsM) were made from Ch and polyethylene oxide (PEO) powders for rich high-porous material with sufficient hemostatic parameters. The structure, porosity, density, antibacterial properties, in vitro degradation and biocompatibility of ChEsM were evaluated and compared to the conventional Ch sponge (ChSp). In addition, the hemostatic and bioactive performance of both materials were examined in vivo, using the liver-bleeding model in rats. A penetrating punch biopsy of the left liver lobe was performed to simulate bleeding from a non-compressible irregular wound. Appropriately shaped ChSp or ChEsM were applied to tissue lesions. Electrospinning allows us to produce high-porous membranes with relevant ChSp degradation and swelling properties. Both materials demonstrated high biocompatibility and hemostatic effectiveness in vitro. However, the antibacterial properties of ChEsM were not as good when compared to the ChSp. In vivo studies confirmed superior ChEsM biocompatibility and sufficient hemostatic performance, with tight interplay with host cells and tissues. The in vivo model showed a higher biodegradation rate of ChEsM and advanced liver repair.
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Massive blood loss is responsible for numerous causes of death. Hemorrhage may occur on the battlefield, at home or during surgery. Commercially available biomaterials may be insufficient to deal with excessive bleeding. Therefore novel, highly efficient hemostatic agents must be developed. The aim of the following research was to obtain a new type of biocompatible chitosan-based hemostatic agents with increased hemostatic properties. The biomaterials were obtained in a quick and efficient manner under microwave radiation using l-aspartic and l-glutamic acid as crosslinking agents with no use of acetic acid. Ready products were investigated over their chemical structure by FT-IR method which confirmed a crosslinking process through the formation of amide bonds. Their high porosity above 90% and low density (below 0.08 g/cm3) were confirmed. The aerogels were also studied over their water vapor permeability and antioxidant activity. Prepared biomaterials were biodegradable in the presence of human lysozyme. All of the samples had excellent hemostatic properties in contact with human blood due to the platelet activation confirmed by blood clotting tests. The SEM microphotographs showed the adherence of blood cells to the biomaterials' surface. Moreover, they were biocompatible with human dermal fibroblasts (HDFs). The biomaterials also had superior antibacterial properties against both Staphylococcus aureus and Escherichia coli. The obtained results showed that proposed chitosan-based hemostatic agents have great potential as a hemostatic product and may be applied under sterile, as well as contaminated conditions, by both medicals and individuals.
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Antibacterianos/química , Antibacterianos/farmacologia , Quitosana/química , Hemostáticos/química , Hemostáticos/farmacologia , Antibacterianos/síntese química , Antioxidantes/síntese química , Antioxidantes/química , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Técnicas de Química Sintética , Hemostáticos/síntese química , Teste de Materiais , Testes de Sensibilidade Microbiana , Estrutura Molecular , Porosidade , Análise Espectral , Relação Estrutura-AtividadeRESUMO
Nanofibrous materials present unique properties favorable in many biomedicine and industrial applications. In this research we evaluated biodegradation, tissue response and general toxicity of nanofibrous poly(lactic acid) (PLA) and polycaprolactone (PCL) scaffolds produced by conventional method of electrospinning and using NanoMatrix3D® (NM3D® ) technology. Mass density, scanning electron microscopy and in vitro degradation (static and dynamic) were used for material characterization, and subcutaneous, intramuscular and intraperitoneal implantation - for in vivo tests. Biochemical blood analysis and histology were used to assess toxicity and tissue response. Pore size and fiber diameter did not differ in conventional and NM3D® PLA and PCL materials, but mass density was significantly lower in NM3D® ones. Scaffolds made by conventional method showed toxic effect during the in-vivo tests due to residual concentration of chloroform that released with material degradation. NM3D® method allowed cleaning scaffolds from residual solutions that made them nontoxic and biocompatible. Subcutaneous, intramuscular and intraperitoneal implantation of PCL and PLA NM3D® electrospun nanofibrous scaffolds showed their appropriate cell conductive properties, tissue and vessels formation in all sites. Thus, NM3D® PCL and PLA nanofibrous electrospun scaffolds can be used in the field of tissue engineering, surgery, wound healing, drug delivery, and so forth, due to their unique properties, nontoxicity and biocompatibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2200-2212, 2018.