RESUMEN
The solid tumors provide a series of biological barriers in cellular microenvironment for designing drug delivery methods based on advanced stimuli-responsive materials. These intertumoral and intratumoral barriers consist of perforated endotheliums, tumor cell crowding, vascularity, lymphatic drainage blocking effect, extracellular matrix (ECM) proteins, hypoxia, and acidosis. Triggering opportunities have been drawn for solid tumor therapies based on single and dual stimuli-responsive drug delivery systems (DDSs) that not only improved drug targeting in deeper sites of the tumor microenvironments, but also facilitated the antitumor drug release efficiency. Single and dual stimuli-responsive materials which are known for their lowest side effects can be categorized in 17 main groups which involve to internal and external stimuli anticancer drug carriers in proportion to microenvironments of targeted solid tumors. Development of such drug carriers can circumvent barriers in clinical trial studies based on their superior capabilities in penetrating into more inaccessible sites of the tumor tissues. In recent designs, key characteristics of these DDSs such as fast response to intracellular and extracellular factors, effective cytotoxicity with minimum side effect, efficient permeability, and rate and location of drug release have been discussed as core concerns of designing paradigms of these materials.
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Antineoplásicos , Sistemas de Liberación de Medicamentos , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos/química , Animales , Nanomedicina Teranóstica/métodosRESUMEN
There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs' long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi.
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Terapia Trombolítica , Trombosis , Activador de Tejido Plasminógeno , Animales , Activador de Tejido Plasminógeno/uso terapéutico , Humanos , Trombosis/diagnóstico por imagen , Trombosis/tratamiento farmacológico , Masculino , Ratas , Terapia Trombolítica/métodos , Trampas Extracelulares/metabolismo , Porcinos , Fibrinolíticos/uso terapéutico , Fibrinolíticos/farmacología , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Fibrina/metabolismo , Nanomedicina Teranóstica/métodos , Resistencia a Medicamentos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/tratamiento farmacológicoRESUMEN
Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3âº-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3âº-MIH and its potential to enhance breast cancer management.
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Neoplasias de la Mama , Imagen por Resonancia Magnética , Nanopartículas , Dióxido de Silicio , Nanomedicina Teranóstica , Dióxido de Silicio/química , Animales , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Femenino , Nanomedicina Teranóstica/métodos , Imagen por Resonancia Magnética/métodos , Ratones , Línea Celular Tumoral , Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Medios de Contraste/química , Gadolinio/química , Porosidad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The burgeoning field of cancer theranostics has witnessed advancements through the development of targeted molecular agents, particularly peptides. These agents exploit the overexpression or mutations of specific receptors, such as the Epidermal Growth Factor receptor (EGFR) and αVß3 integrin, which are pivotal in tumor growth, angiogenesis, and metastasis. Despite the extensive research into and promising outcomes associated with antibody-based therapies, peptides offer a compelling alternative due to their smaller size, ease of modification, and rapid bioavailability, factors which potentially enhance tumor penetration and reduce systemic toxicity. However, the application of peptides in clinical settings has challenges. Their lower binding affinity and rapid clearance from the bloodstream compared to antibodies often limit their therapeutic efficacy and diagnostic accuracy. This overview sets the stage for a comprehensive review of the current research landscape as it relates to EGFR- and integrin αVß3-targeting peptides. We aim to delve into their synthesis, radiolabeling techniques, and preclinical and clinical evaluations, highlighting their potential and limitations in cancer theranostics. This review not only synthesizes the extant literature to outline the advancements in peptide-based agents targeting EGFR and integrin αVß3 but also identifies critical gaps that could inform future research directions. By addressing these gaps, we contribute to the broader discourse on enhancing the diagnostic precision and therapeutic outcomes of cancer treatments.
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Receptores ErbB , Integrina alfaVbeta3 , Neoplasias , Péptidos , Radiofármacos , Humanos , Integrina alfaVbeta3/metabolismo , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Radiofármacos/uso terapéutico , Radiofármacos/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Péptidos/química , Péptidos/uso terapéutico , Animales , Medicina de Precisión/métodos , Nanomedicina Teranóstica/métodosRESUMEN
The advancements in nanotechnology, pharmaceutical sciences, and healthcare are propelling the field of theranostics, which combines therapy and diagnostics, to new heights; emphasizing the emergence of selenium nanoparticles (SeNPs) as versatile theranostic agents. This comprehensive update offers a holistic perspective on recent developments in the synthesis and theranostic applications of SeNPs, underscoring their growing importance in nanotechnology and healthcare. SeNPs have shown significant potential in multiple domains, including antioxidant, anti-inflammatory, anticancer, antimicrobial, antidiabetic, wound healing, and cytoprotective therapies. The review highlights the adaptability and biocompatibility of SeNPs, which are crucial for advanced disease detection, monitoring, and personalized treatment. Special emphasis is placed on advancements in green synthesis techniques, underscoring their eco-friendly and cost-effective benefits in biosensing, diagnostics, imaging and therapeutic applications. Additionally, the appraisal scrutinizes the progressive trends in smart stimuli-responsive SeNPs, conferring their role in innovative solutions for disease management and diagnostics. Despite their promising therapeutic and prophylactic potential, SeNPs also present several challenges, particularly regarding toxicity concerns. These challenges and their implications for clinical translation are thoroughly explored, providing a balanced view of the current state and prospects of SeNPs in theranostic applications.
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Tecnología Química Verde , Nanopartículas , Selenio , Nanomedicina Teranóstica , Selenio/química , Humanos , Nanomedicina Teranóstica/métodos , Tecnología Química Verde/métodos , AnimalesRESUMEN
The diagnosis of neurodegenerative diseases (NDDs) remains challenging, and existing therapeutic approaches demonstrate little efficacy. NDD drug delivery can be achieved through the utilization of nanostructures, hence enabling multimodal NDD theranostics. Nevertheless, both biomembrane and non-biomembrane nanostructures possess intrinsic shortcomings that must be addressed by hybridization to create novel nanostructures with versatile applications in NDD theranostics. Hybrid nanostructures display improved biocompatibility, inherent targeting capabilities, intelligent responsiveness, and controlled drug release. This paper provides a concise overview of the latest developments in hybrid nanostructures for NDD theranostics and emphasizes various engineering methodologies for the integration of diverse nanostructures, including liposomes, exosomes, cell membranes, and non-biomembrane nanostructures such as polymers, metals, and hydrogels. The use of a combination technique can significantly augment the precision, intelligence, and efficacy of hybrid nanostructures, therefore functioning as a more robust theranostic approach for NDDs. This paper also addresses the issues that arise in the therapeutic translation of hybrid nanostructures and explores potential future prospects in this field.
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Nanoestructuras , Enfermedades Neurodegenerativas , Nanomedicina Teranóstica , Humanos , Nanomedicina Teranóstica/métodos , Nanomedicina Teranóstica/tendencias , Nanoestructuras/uso terapéutico , Enfermedades Neurodegenerativas/terapia , Enfermedades Neurodegenerativas/diagnóstico por imagen , Sistemas de Liberación de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/tendencias , AnimalesRESUMEN
BACKGROUND: Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging. METHODS: Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice. RESULTS: Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission. CONCLUSION: This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.
Asunto(s)
Cerio , Curcumina , Ácido Hialurónico , Enfermedades Inflamatorias del Intestino , Nanopartículas , Nanomedicina Teranóstica , Animales , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Ratones , Cerio/química , Curcumina/farmacología , Curcumina/química , Curcumina/uso terapéutico , Nanomedicina Teranóstica/métodos , Administración Oral , Nanopartículas/química , Ácido Hialurónico/química , Hialuronoglucosaminidasa/metabolismo , Tomografía Computarizada por Rayos X , Ratones Endogámicos C57BL , Colon/diagnóstico por imagen , Colon/patología , Colon/metabolismo , Humanos , Colitis/tratamiento farmacológicoRESUMEN
The advancement of theranostics, which combines therapeutic and diagnostic capabilities in oncology, has significantly impacted cancer management. This review explores fibroblast activation protein (FAP) expression in the tumor microenvironment (TME) and its association with various malignancies, highlighting its potential as a theranostic marker for PET/CT imaging using FAP-targeted tracers and for FAP-targeted radiopharmaceutical therapy. We examine the development and clinical applications of FAP inhibitors (FAPIs) and peptides, providing insights into their diagnostic accuracy, initial therapeutic efficacy, and clinical impact across diverse cancer types, as well as the synthesis of novel FAP-targeted ligands. This review aims to showcase the promising outcomes and challenges in integrating FAP-targeted approaches into cancer management.
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Proteínas de la Membrana , Péptidos , Humanos , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/antagonistas & inhibidores , Serina Endopeptidasas/metabolismo , Endopeptidasas/metabolismo , Animales , Gelatinasas/metabolismo , Gelatinasas/antagonistas & inhibidores , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Neoplasias/metabolismo , Nanomedicina Teranóstica/métodos , Medicina de Precisión/métodos , Microambiente Tumoral , Radiofármacos/uso terapéuticoRESUMEN
The perfect integration of microbubbles for efficient ultrasound imaging and nanocarriers for intelligent tumor-targeting delivery remains a challenge in precise tumor theranostics. Herein, we exquisitely fabricated laser-activated and targeted polymersomes (abbreviated as FIP-NPs) for simultaneously encapsulating the photosensitizer indocyanine green (ICG) and the phase change agent perfluorohexane (PFH). The formulated FIP-NPs were nanosize and effectively accumulated into tumors as observed by ICG fluorescence imaging. When the temperature rose above 56 °C, the encapsulated PFH transformed from liquid to gas and the FIP-NPs underwent balloon-like enlargement without structure destruction. Impressively, the enlarged FIP-NPs fused with adjacent polymersomes to form even larger microparticles. This temperature-responsive "nano-to-micro" transformation and fusion process was clearly demonstrated, and FIP-NPs showed greatly improved ultrasound signals. More importantly, FIP-NPs achieved dramatic antitumor efficacy through ICG-mediated phototherapy. Taken together, the novel polymersomes achieved excellent ultrasound/fluorescence dual imaging-guided tumor phototherapy, providing an optimistic candidate for the application of tumor theranostics.
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Verde de Indocianina , Imagen Óptica , Fototerapia , Polímeros , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Animales , Ratones , Fototerapia/métodos , Humanos , Imagen Óptica/métodos , Polímeros/química , Nanopartículas/química , Nanopartículas/uso terapéutico , Fluorocarburos/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Temperatura , Ultrasonografía/métodos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Nanomedicina Teranóstica/métodos , Microburbujas/uso terapéuticoRESUMEN
Near-infrared (NIR) phototherapies offer noninvasive, cost-effective solutions for treating tumors and microbial infections. However, organic NIR dyes commonly used suffer from solubility and stability issues requiring frequent dosing. We address this challenge by exploring the bacteriophage-mediated enhancement of NIR dye properties. Upon encapsulation within phage nanosomes, IR780 and Indocyanine green (ICG), with similar optical properties but distinct water solubility and exhibit enhanced UV-vis absorbance and photothermal transduction efficacy compared to liposomes. Experimental characterization corroborated with all-atom molecular dynamics simulations imprints the nanoscale structure, solubility, dynamics, and binding of these NIR dye molecules to the membrane and protein molecules present in Phage capsid. These NIR dye-loaded phage nanosomes, coencapsulated with mitoxantrone, demonstrate enhanced anticancer activity, and when combined with amphotericin B, these dye molecules exhibit superior photothermal effects against fungal infections. Our findings present a simple and efficient approach for tuning the photothermal performance of existing NIR dyes through a rational design for enhanced therapeutic outcomes.
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Verde de Indocianina , Rayos Infrarrojos , Verde de Indocianina/química , Verde de Indocianina/farmacología , Humanos , Nanomedicina Teranóstica/métodos , Colorantes/química , Colorantes/farmacología , Indoles/química , Indoles/farmacología , Mitoxantrona/química , Mitoxantrona/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Simulación de Dinámica MolecularRESUMEN
Combination therapy using chemo-photothermal therapy (chemo-PTT) shows great efficacy toward tumor ablation in preclinical studies. Besides, lipopolymersomes as a hybrid nanocarriers, integrate advantages of liposomes and polymersomes in a single platform in order to provide tremendous biocompatibility, biodegradability, noteworthy loading efficacy for both hydrophobic and hydrophilic drugs with adjustable drug release and high stability. In this study, a multipurpose lipopolymersome was fabricated for guided chemotherapy-PTT and NIR-imaging of melanoma. A lipopolymerosomal hybrid nanovesicle consisting of equal molar ratio of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and poly (ethylene glycol)-poly (lactic acid) (PEG-PLA) diblock copolymer (molar ratio 1:1) was fabricated. The nanoparticulate system was prepared through film rehydration technique for encapsulation of doxorubicin (DOX) and indocyanine green (ICG) to form DOX-ICG-LP platform. At the next stage, AS1411 DNA aptamer was conjugated to the surface of lipopolymersome (Apt-DOX-ICG-LP) for selective delivery. The sizes of DOX-ICG-LP and Apt-DOX-ICG-LP were obtained through DLS analysis (61.0 ± 6 and 74 ± 5, respectively). Near Infrared-responsive release pattern of the prepared lipopolymersome was verified in vitro. The formulated platform showed efficient photothermal conversion, and superior stability with acceptable encapsulation efficiency. Consistent with the in vitro studies, NIR-responsive lipopolymersome exhibited significantly higher cellular toxicity for Chemo-PTT versus single anti-cancer treatment. Moreover, superlative tumor shrinkage with favorable survival profile were attained in B16F10 tumor-bearing mice received Apt-DOX-ICG-LP and irradiated with 808 nm laser compared to those treated with either DOX-ICG-LP or Apt-DOX-ICG-LP without laser irradiation. The diagnostic capability of Apt-DOX-ICG-LP was addressed using in vivo NIR imaging, 6 and 24 h post-intravenous administration. The results indicated desirable feature of an established targeted theranostic capability of Apt-DOX-ICG-LP for both diagnostics and dual chemo-PTT of melanoma.
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Doxorrubicina , Verde de Indocianina , Terapia Fototérmica , Polietilenglicoles , Nanomedicina Teranóstica , Animales , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Verde de Indocianina/administración & dosificación , Ratones , Polietilenglicoles/química , Terapia Fototérmica/métodos , Línea Celular Tumoral , Nanomedicina Teranóstica/métodos , Portadores de Fármacos/química , Liberación de Fármacos , Nanopartículas/química , Compuestos de Amonio Cuaternario/química , Humanos , Liposomas , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/terapia , Melanoma/tratamiento farmacológico , Melanoma/terapia , Polímeros/química , Poliésteres/química , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacología , Ratones Endogámicos C57BL , Fototerapia/métodos , Ácidos Grasos MonoinsaturadosRESUMEN
Cardiotoxicity, the often-overlooked second leading cause of death in cancer patients, has been associated with certain anticancer drugs. These drugs can induce cardiac damage through various pathways, and their adverse effects on the heart are not fully understood. Cardiotoxicity is a major issue in cancer treatment, particularly with chemotherapeutics, because it can cause cardiac dysfunction such as hypotension, heart failure, and even death. Doxorubicin, 5-fluorouracil, and trastuzumab, all of which are very potent anticancer drugs, are known to cause cardiotoxicity. When it comes to lowering cardiotoxicity and alleviating the harmful effects of chemotherapy medications, nanomedicine has the potential to transport therapeutic molecules. Nanotheranostics offers novel options for identifying and treating cardiotoxicity resulting from a wide range of substances, including anticancer medications. Additionally, theranostics platforms such as micellar systems, carbon-based nanomedicine, solid lipid nanoparticles, polymeric nanoparticles, and liposomes can transport chemotherapeutic medications while minimising their cardiotoxicity. The present level of understanding of the molecular and cellular processes that lead to cardiotoxicity in reaction to both traditional chemotherapy and targeted drug delivery systems is summarised in this article. This review delves into nanomedicine and nanotheranostics, with an emphasis on reducing anticancer medication-induced cardiac toxicity. Nanotheranostics provide potential solutions for early diagnosis and tailored therapy of heart injury by combining diagnostic and therapeutic capabilities into nanomedicine.
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Antineoplásicos , Cardiotoxicidad , Nanomedicina , Nanomedicina Teranóstica , Humanos , Antineoplásicos/efectos adversos , Antineoplásicos/química , Cardiotoxicidad/etiología , Nanomedicina/métodos , Nanomedicina Teranóstica/métodos , Animales , Cardiopatías/inducido químicamente , Neoplasias/tratamiento farmacológico , Nanopartículas/químicaRESUMEN
BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.
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Clorofilidas , Imagen Multimodal , Fármacos Fotosensibilizantes , Placa Aterosclerótica , Porfirinas , Tomografía de Coherencia Óptica , Animales , Placa Aterosclerótica/diagnóstico por imagen , Conejos , Imagen Multimodal/métodos , Tomografía de Coherencia Óptica/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Macrófagos/metabolismo , Nanomedicina Teranóstica/métodos , Ratones , Masculino , Autofagia , Tirosina Quinasa c-Mer/metabolismo , ApoptosisRESUMEN
In this study, we developed new gadolinium-graphene quantum dot nanoparticles (Gd-GQDs) as a theranostic platform for magnetic resonance imaging and improved the efficiency of radiotherapy in HPV-positive oropharyngeal cancer. Based on cell toxicity results, Gd-GQD NPs were nontoxic for both cancer and normal cell lines up to 25 µg/ml. These NPs enhance the cytotoxic effect of radiation only on cancer cells but not on normal cells. The flow cytometry analysis indicated that cell death mainly occurred in the late phase of apoptosis. The immunocytochemical analysis was used to evaluate apoptosis pathway proteins. The Bcl-2 and p53 protein levels did not differ statistically significantly between radiation alone group and those that received irradiation in combination with NPs. In contrast, the combination group exhibited a significant increase in Bax protein expression, suggesting that cells could undergo apoptosis independent of the p53 pathway. Magnetic resonance (MR) imaging showed that Gd-GQD NPs, when used at low concentrations, enhanced T1-weighted signal intensity resulting from T1 shortening effects. At higher concentrations, the T2 shortening effect became predominant and was able to decrease the signal intensity. Gd-GQD appears to offer a novel approach for enhancing the effectiveness of radiation treatment and facilitating MR imaging for monitoring HPV-positive tumors.
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Gadolinio , Imagen por Resonancia Magnética , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Puntos Cuánticos , Humanos , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/radioterapia , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Imagen por Resonancia Magnética/métodos , Apoptosis/efectos de los fármacos , Nanomedicina Teranóstica/métodos , Línea Celular TumoralRESUMEN
To maintain a clean and hygienic environment in the intensive care unit (ICU) is crucial for ensuring patient safety, preventing infections, and reducing healthcare-associated complications. With the increasing prevalence of infections and the emergence of viral and bacterial resistance to standard antiseptics, there is a pressing need for innovative antiseptic solutions. Nanotechnology is increasingly being employed in medicine, particularly focusing on mitigating the activities of various pathogens, including those associated with hospital-acquired infections. This paper explores the current impact of nanotechnology, with a particular focus on bacterial infections and SARS-CoV-2, which significantly strain healthcare systems, and then discusses how nanotechnology can enhance existing treatment methodologies. We highlight the effectiveness of the nanotechnology-based bactericide Bio-Kil in reducing bacterial counts in an ICU. The aim is to educate healthcare professionals on the existing role and prospects of nanotechnology in addressing prevalent infectious diseases.
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COVID-19 , Unidades de Cuidados Intensivos , Nanotecnología , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Nanotecnología/métodos , Infecciones Bacterianas/tratamiento farmacológico , Infección Hospitalaria/prevención & control , Nanomedicina Teranóstica/métodos , SARS-CoV-2RESUMEN
The commonly employed strategies for engineering second near-infrared (NIR-II) organic phototheranostic agents are based on expanding conjugated backbone length, strengthening donor (D)-acceptor (A) effect, or forming J-aggregates. We constructed the D-A-D' structure by incorporating strong electron-donating methoxy and tetraphenylethene (TPE) moieties on the electron-deficient Aza-BODIPY core, and simultaneously expanded the π-conjugation effect by introducing thiophene groups, to obtain a dye BDP-TPE. Next, the nanoparticles P-TPE were prepared via the assembly of BDP-TPE with amphiphilic polypeptides (mPEG2000-P(Asp)10), and successfully constructed the J-aggregates. The obtained P-TPE exhibited strong absorption and fluorescence with maxima at 808 and 1018 nm, respectively, with a conspicuous absolute quantum yield of 0.241 %. Moreover, P-TPE also showed excellent biocompatibility, and high photothermal conversion efficiency of 61.15 %, and excellent resistance to pH, long-term storage, and photobleaching. In vitro and in vivo experiments revealed that P-TPE exhibited good biocompatibility and effectively achieved NIR-II fluorescence imaging-guided PTT with complete tumor ablation under 808 nm laser irradiation. These results provided good evidence for the use of P-TPE as a NIR-II fluorescence imaging-guided PTT therapeutic agent in vivo.
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Compuestos de Boro , Electrones , Péptidos , Compuestos de Boro/química , Animales , Humanos , Péptidos/química , Ratones , Rayos Infrarrojos , Nanomedicina Teranóstica/métodos , Nanopartículas/química , Fototerapia/métodos , Línea Celular TumoralRESUMEN
The lack of a simple design strategy to obtain ideal conjugated polymers (CPs) with high absorbance and fluorescence (FL) in the near-infrared-II (NIR-II; 1000-1700 nm) region still hampers the success of NIR-II light-triggered phototheranostics. Herein, novel phototheranostic nanoparticles (PPN-NO NPs) were successfully prepared by coloading a cationic NIR-II CPs (PBC-co-PBF-NMe3) and a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) onto a 1:1 mixture of DSPE-PEG5000 and dimyristoylphosphatidylcholine (DMPC) for NIR-II FL and NIR-II photoacoustic (PA) imaging-guided low-temperature NIR-II photothermal therapy (PTT) and gas combination therapy for cancer treatment. A precise NIR-II FL dually enhanced design tactic was proposed herein by integrating flexible nonconjugated segments (C6) into the CPs backbone and incorporating quaternary ammonium salt cationic units into the CPs side chain, which considerably increased the radiative decay pathway, resulting in desirable NIR-II FL intensity and balanced NIR-II absorption and NIR PTT properties. The phototheranostic PPN-NO NPs exhibited distinguished NIR-II FL and PA imaging performance in tumor-bearing mice models. Furthermore, the low-temperature photothermal effect of PPN-NO NPs could initiate NO release upon 980 nm laser irradiation, efficiently suppressing tumor growth owing to the combination of low-temperature NIR-II PTT and NO gas therapy in vitro and in vivo.
Asunto(s)
Cationes , Nanopartículas , Terapia Fototérmica , Polímeros , Animales , Ratones , Polímeros/química , Terapia Fototérmica/métodos , Humanos , Nanopartículas/química , Cationes/química , Rayos Infrarrojos , Ratones Endogámicos BALB C , Línea Celular Tumoral , Fluorescencia , Técnicas Fotoacústicas/métodos , Ratones Desnudos , Femenino , Nanomedicina Teranóstica/métodosRESUMEN
Background: Influenza A (H1N1) virus is a highly contagious respiratory disease that causes severe illness and death. Vaccines and antiviral drugs are limited by viral variation and drug resistance, so developing efficient integrated theranostic options appears significant in anti-influenza virus infection. Methods: In this study, we designed and fabricated covalent organic framework (COF) based theranostic platforms (T705@DATA-COF-Pro), which was composed of an RNA polymerase inhibitor (favipiravir, T705), the carboxyl-enriched COF (DATA-COF) nano-carrier and Cy3-labeled single DNA (ssDNA) probe. Results: The multi-porosity COF core provided an excellent micro-environment and smooth delivery for T705. The ssDNA probe coating bound to the nucleic acids of H1N1 selectively, thus controlling drug release and allowing fluorescence imaging. The combination of COF and probe triggered the synergism, promoting drug further therapeutic outcomes. With the aid of T705@DATA-COF-Pro platforms, the H1N1-infected mouse models lightly achieved diagnosis and significantly prolonged survival. Conclusion: This research underscores the distinctive benefits and immense potential of COF materials in nano-preparations for virus infection, offering novel avenues for the detection and treatment of H1N1 virus infection.
Asunto(s)
Antivirales , Subtipo H1N1 del Virus de la Influenza A , Estructuras Metalorgánicas , Infecciones por Orthomyxoviridae , Nanomedicina Teranóstica , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Animales , Nanomedicina Teranóstica/métodos , Antivirales/química , Antivirales/farmacología , Antivirales/uso terapéutico , Ratones , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Humanos , Amidas/química , Amidas/farmacología , Pirazinas/química , Pirazinas/farmacología , Pirazinas/farmacocinética , Pirazinas/uso terapéutico , Gripe Humana/tratamiento farmacológico , Ratones Endogámicos BALB C , Células de Riñón Canino Madin Darby , Portadores de Fármacos/química , Perros , Liberación de FármacosRESUMEN
Bioluminescence, the light produced by biochemical reactions involving luciferases in living organisms, has been extensively investigated for various applications. It has attracted particular interest as an internal light source for theranostic applications due to its safe and efficient characteristics that overcome the limited penetration of conventional external light sources. Recent advancements in protein engineering technologies and protein delivery platforms have expanded the application of bioluminescence to a wide range of theranostic areas, including bioimaging, biosensing, photodynamic therapy, and optogenetics. This comprehensive review presents the fundamental concepts of bioluminescence and explores its recent applications across diverse fields. Moreover, it discusses future research directions based on the current status of bioluminescent systems for further expansion of their potential.