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1.
Small ; : e2402265, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38757418

RESUMO

The emerging applications of thermally conductive elastomer composites in modern electronic devices for heat dissipation require them to maintain both high toughness and resilience under thermomechanical stresses. However, such a combination of thermal conductivity and desired mechanical characteristics is extremely challenging to achieve in elastomer composites. Here this long-standing mismatch is resolved via regulating interfacial structure and dynamics response. This regulation is realized both by tuning the molecular weight of the dangling chains in the polymer networks and by silane grafting of the fillers, thereby creating a broad dynamic-gradient interfacial region comprising of entanglements. These entanglements can provide the slipping topological constraint that allows for tension equalization between and along the chains, while also tightening into rigid knots to prevent chain disentanglement upon stretching. Combined with ultrahigh loading of aluminum-fillers (90 wt%), this design provides a low Young's modulus (350.0 kPa), high fracture toughness (831.5 J m-2), excellent resilience (79%) and enhanced thermal conductivity (3.20 W m-1 k-1). This work presents a generalizable preparation strategy toward engineering soft, tough, and resilient high-filled elastomer composites, suitable for complex environments, such as automotive electronics, and wearable devices.

2.
Int J Oral Sci ; 16(1): 21, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424060

RESUMO

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.


Assuntos
Ameloblastoma , Humanos , Ameloblastoma/genética , Ameloblastoma/patologia , Recidiva Local de Neoplasia , Fenótipo , Transformação Celular Neoplásica , Perfilação da Expressão Gênica
3.
Phys Chem Chem Phys ; 26(5): 4429-4436, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38240037

RESUMO

Most tough elastomer composites are reinforced by introducing sacrificial structures and fillers. Understanding the contribution of fillers and sacrificial bonds in elastomer composites to the energy dissipation is critical for the design of high-toughness materials. However, the energy dissipation mechanism in elastomer composites remains elusive. In this study, using a tearing test and time-temperature superposition, we investigate the effect of fillers and sacrificial bonds on the energy dissipation of elastomer composites consisting of poly(lipoic acid)/silver-coated Al fillers. We found that the fillers and sacrificial bonds mutually enhance both the intrinsic fracture energy and the bulk energy dissipation, and moreover the sacrificial bonds play a more important role in enhancing fracture toughness than the fillers. It is unreasonable to rely solely on the loss factor for bulk energy dissipation. The addition of sacrificial bonds results in a chain segment experiencing greater binding force compared to the addition of fillers. This suggests that the chain segment consumes more energy during its movement. By calculating the length of the Kuhn chain segment and the Kuhn number, it is evident that the addition of sacrificial bonds results in a greater binding force for the chain segment than the addition of fillers, and this enhanced binding force increases the energy consumption during the motion of the chain segment.

4.
Small ; 20(2): e2305090, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37658523

RESUMO

The pursuit of enhancing the heat transfer performance of composite elastomers as the thermal interface materials (TIMs) is a compelling and timely endeavor, given the formidable challenges posed by interfacial thermal transport in the domains of energy science, electronic technology, etc. Despite the efficacy of phase change materials (PCMs) in enhancing composite elastomers' interfacial compatibility, thereby reducing contact thermal resistance for heat transfer improvement, their leakage post-transition has impeded the widespread adoption of this approach. Herein, a strategy is proposed for developing a solid-solid phase change composite elastomer by grafting alkene chains onto the crosslink network to eliminate the possibility of leakage. A series characterization suggest that the resulting material possesses a self-adjusting interfacial compatibility feature to help reduce contact thermal resistance for heat transfer facilitating. The investigations on adhesion strength and surface energy reveal that the presence of amorphous grafted alkane chains at the interface facilitates easier absorption onto the contacting solid surface, enhancing intermolecular interactions at the interface to promote across-boundary heat transfer. By integrating these findings with the thermal performance evaluation of composite elastomers using a real test vehicle, valuable insights are gained for the design of composite elastomers, establishing their suitability as TIMs in relevant fields.

6.
Small ; 20(22): e2306946, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38133511

RESUMO

Modern microelectronics and emerging technologies such as wearable electronics and soft robotics require elastomers to integrate high damping with low thermal resistance to avoid damage caused by vibrations and heat accumulation. However, the strong coupling between storage modulus and loss factor makes it generally challenging to simultaneously increase both thermal conductance and damping. Here, a strategy of introducing hierarchical interaction and regulating fillers in polybutadiene/spherical aluminum elastomer composites is reported to simultaneously achieve extraordinary damping ability of tan δ > 1.0 and low thermal resistance of 0.15 cm2 K W-1, which surpasses state-of-the-art elastomers and their composites. The enhanced damping is attributed to increased energy dissipation via introducing the hierarchical hydrogen bond interactions in polybutadiene networks and the addition of spherical aluminum, which also functions as a thermally conductive filler to achieve low thermal resistance. As a proof of concept, the polybutadiene/spherical aluminum elastomer composites are used as thermal interface materials, showing effective heat dissipation for electronic devices in vibration scenarios. The combination of outstanding damping performance and extraordinary heat dissipation ability of the elastomer composites may create new opportunities for their applications in electronics.

7.
World J Gastrointest Oncol ; 15(11): 1852-1863, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38077649

RESUMO

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis, early metastasis, and poor prognosis. Because current therapeutic options are limited, there is an urgent need to investigate novel targeted treatment strategies. Pancreatic cancer faces significant metabolic challenges, principally hypoxia and nutrient deprivation, due to specific microenvironmental constraints, including an extensive desmoplastic stromal reaction. Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation. Increased glucose uptake and glycolytic pathway activity during this process have been extensively described. However, growing evidence suggests that pancreatic cancer cells are glutamine addicted. As a nitrogen source, glutamine directly (or indirectly via glutamate conversion) contributes to many anabolic processes in pancreatic cancer, including amino acids, nucleobases, and hexosamine biosynthesis. It also plays an important role in redox homeostasis, and when converted to α-ketoglutarate, glutamine serves as an energy and anaplerotic carbon source, replenishing the tricarboxylic acid cycle intermediates. The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer, focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38044636

RESUMO

DNA nanomachines could initiate the cascade reaction in an autonomous mode under the drive of triggers, which achieve the signal amplification for the bioimaging of intracellular biomarkers. Compared with the "always-on" nanomachine that possibly produces false-positive signals, a controllable nanomachine with the on-site activation could be better for accurate tumor imaging and precise tumor therapy. Till now, the endogenous and exogenous triggers have been developed to design the controllable nanosensors. However, their combinations to develop feasible DNA nanomachines have been rarely studied. Herein, we constructed a near-infrared (NIR)-light-controlled DNA nanomachine that was first activated by the NIR light and then induced a target-triggered amplification process under the drive of an endogenous stimulus. Owing to adenosine-5'-triphosphate (ATP) having much higher concentration in cancer cells than that in healthy cells and the extracellular fluid, the obtained DNA nanomachine was selectively activated in cancer cells with inhibited interference signals from the surrounding healthy tissues. With obvious advantages including the exogenous NIR light initiation, the selective activation by the target microRNA, and the sensitive acceleration by the ATP-induced strand recycling reaction, the constructed nanomachine could be used to image the intracellular microRNA with increased sensitivity. Besides, after modifying the DNA sequence with the photosensitizer molecules, the obtained nanomachine could perform the selective photodynamic therapy on the tumor sections with the outstandingly decreased side effects. Thus, we hope the designed nanomachine could provide some important hints to design feasible nanomachines for accurate tumor diagnosis and precise tumor therapy.

9.
ACS Appl Mater Interfaces ; 15(36): 43169-43182, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37667856

RESUMO

The interfacial thermal resistance (ITR) inside the particulate-filled polymer composite is a bottleneck for improving the thermal conductivity (TC) of the material. Getting full knowledge of the ITR is crucial to the material design as well as to a faithful prediction of TC of the composite. However, a method fully taking into account the local circumstances inside the composite is yet to be developed to precisely characterize the ITR. Here, we propose a comprehensive framework combining high-throughput numerical simulations, machine learning and optimization algorithms, and experiments, which is demonstrated to be robust for the accurate determination of ITRs inside the particulate-filled composites. The strategy extracts as much information as possible about the structure and heat transfer characteristics of the composite based on simple experiments, which lays the foundation for the method to be effective. We show that the polymer-filler ITRs and the effective filler-filler contact ITRs predicted with the method faithfully represent the true characteristics inside the composite materials; they also provide the exact effective parameters, which cannot be obtained from experiments, for accurate numerical prediction of TCs of composite materials with high efficiency. As a result, the framework not only provides a robust tool for accurate characterization of ITRs inside composites but also paves the way for virtual high-throughput formula screening of thermally conductive composite materials that could be used in industrial product design.

10.
Arch Iran Med ; 26(3): 172-175, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-37543940

RESUMO

Inflammatory bowel disease (IBD) is associated with body composition changes, which are associated with clinical prognosis, response to therapy, and quality of life in IBD patients. Therefore, it is critical to review the body composition distribution in IBD, summarize the potential factors affecting body composition distribution, and take steps to improve the body composition distribution of IBD patients as early as possible. In the current review, we searched PubMed via keywords 'inflammatory bowel disease', or 'IBD', or 'Crohn's disease', or 'CD', or 'ulcerative colitis', or 'UC', and 'body composition'. Malnutrition and sarcopenia are common in IBD patients and are associated with the clinical course, prognosis, and need for surgery. Disease activity, reduced nutrition intake, vitamin D deficiency, and intestinal dysbiosis are factors contributing to changed body composition. Early use of biological agents to induce remission is critical to improving body composition distribution in IBD patients, supplementation of vitamin D is also important, and moderate physical activity is recommended in IBD patients with clinical remission.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Qualidade de Vida , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Vitamina D/uso terapêutico
11.
Nano Lett ; 23(14): 6673-6680, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37428875

RESUMO

Thermal resistance at a soft/hard material interface plays an undisputed role in the development of electronic packaging, sensors, and medicine. Adhesion energy and phonon spectra match are two crucial parameters in determining the interfacial thermal resistance (ITR), but it is difficult to simultaneously achieve these two parameters in one system to reduce the ITR at the soft/hard material interface. Here, we report a design of an elastomer composite consisting of a polyurethane-thioctic acid copolymer and microscale spherical aluminum, which exhibits both high phonon spectra match and high adhesion energy (>1000 J/m2) with hard materials, thus leading to a low ITR of 0.03 mm2·K/W. We further develop a quantitative physically based model connecting the adhesion energy and ITR, revealing the key role the adhesion energy plays. This work serves to engineer the ITR at the soft/hard material interface from the aspect of adhesion energy, which will prompt a paradigm shift in the development of interface science.

12.
J Cell Mol Med ; 27(19): 2937-2944, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37499109

RESUMO

Colorectal cancer (CRC) is identified as a primary cause of death around the world. The current chemotherapies are not cost-effective. Therefore, finding novel potential therapeutic target is urgent. Titin (TTN) is a muscle protein that is critical in hypertrophic cardiomyopathy. However, its role in CRC is not well understood. The study focused on exploring the possible role of TTN in CRC carcinogenesis. TTN mRNA and protein expression levels presented an obvious downregulation in CRC tissue samples, relative to normal control (p < 0.05). TTN expression significantly correlated with the clinical stage (normal vs. Stage 1, p < 0.05; normal vs. Stage 4, p < 0.05), node metastasis (normal vs. N1, p < 0.05; N1 vs. N2, p < 0.05), histological type (normal vs. adenocarcinoma, p < 0.05), race (Caucasian vs. Asian, p < 0.05; African-American vs. Asian, p < 0.05) and TP53 mutation (normal vs. TP53 mutation, p < 0.05), considering The Cancer Genome Atlas database. However, for patients who had higher TTN expression, the overall survival was remarkably shorter than patients who had low TTN expression. Furthermore, TTN was lowly expressed in four CRC cell lines. TTN overexpression facilitated CRC cells in terms of the proliferation, metastasis and invasion. Based on gene set enrichment analysis, the ERB pathway might be responsible for TTN-related CRC. Besides, TTN was involved in the response to azacitidine. Overall, TTN might serve as a potential novel therapeutic target for treating and overcoming chemotherapy resistance in CRC.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , Conectina/genética , Conectina/metabolismo , MicroRNAs/genética , Proteínas Musculares/genética , Mutação/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo
13.
World J Gastrointest Endosc ; 15(4): 240-247, 2023 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-37138936

RESUMO

Gastric signet-ring cell gastric carcinoma (GSRC) is an unfavorable subtype of gastric cancer (GC) that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC. However, GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC. Therefore, the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients. In recent years, technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients. Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection (ESD), indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation. This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.

14.
Nanoscale ; 15(19): 8706-8715, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37009676

RESUMO

Interfacial binding and phonon mismatch are two crucial parameters in determining thermal boundary conductance. However, it is difficult for polymer/metal interfaces to possess both significant interfacial binding and weak phonon mismatch to achieve enhanced thermal boundary conductance. Herein, we circumvent this inherent trade-off by synthesizing a polyurethane and thioctic acid (PU-TA) copolymer with multiple hydrogen bonds and dynamic disulfide bonds. Using PU-TA/aluminum (Al) as a model interface, we demonstrate that the thermal boundary conductance of the PU-TA/Al interfaces measured by transient thermoreflectance is 2-5 times higher than that of traditional polymer/Al interfaces, which is attributed to the highly matched and bonded interface. Furthermore, a correlation analysis is developed, which demonstrates that interfacial binding has a greater impact than phonon mismatch on thermal boundary conductance at a highly matched interface. This work provides a systematic understanding of the relative contributions of the two dominant mechanisms to thermal boundary conductance by tailoring the polymer structure, which has applications in thermal management materials.

15.
Anal Chem ; 95(13): 5601-5609, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36960746

RESUMO

The construction of a sensitive strategy for in situ visualizing and dynamic tracing intracellular microRNA is of great importance. Via the toehold-mediated strand displacement process, the catalytic hairpin assembly (CHA) could offer several hundreds-fold signal amplifications. However, the CHA may produce certain background interferences since microRNA may exist in normal cells. In this work, we constructed an endogenously and sequentially activated signal amplification strategy to provide the amplified dual-color fluorescence imaging of microRNA in living cancer cells, which was comprised of two successive reaction processes: the activation of the preprotective catalytic probe by the endogenous glutathione (GSH) and the subsequent catalytic hairpin assembly on the surface of the upconversion nanoprobe triggered by the specific microRNA. Since the concentration of GSH in cancer cells was much higher than that in normal cells and the extracellular environment, the activation of the designed nanoprobe could be controlled at the desirable site. With the merits of the endogenous initiation and selective activation, the designed nanoprobe could achieve the bioimaging of microRNA in living cancer cells with high precision and reliability. Furthermore, via the introduction of a photosensitizer molecule into the DNA strand, the designed nanoplatform could achieve the precise photodynamic therapy (PDT) for cancer cells and malignant tumors under the irradiation of the NIR laser. This work provided a new avenue to achieve the accurate imaging of intracellular microRNA and guided precise PDT, which would offer powerful hints to the early diagnosis and therapy of malignant tumors.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Neoplasias , Fotoquimioterapia , MicroRNAs/genética , Reprodutibilidade dos Testes , Fármacos Fotossensibilizantes/farmacologia , DNA , Técnicas Biossensoriais/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
16.
Eur J Gastroenterol Hepatol ; 35(4): 376-383, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36827532

RESUMO

BACKGROUND AND PURPOSE: Although endoscopic submucosal dissection (ESD) is considered standard treatment for early gastric cancer (EGC), patients with non-curative resection (NCR) of ESD may still require gastrectomy. The systemic immune-inflammation index (SII) showed great potential in predicting the prognosis of gastric cancer patients. This study aims to investigate the predictive validity of SII of NCR in EGC patients. METHODS: We reviewed data from EGC patients who underwent ESD in the past. The relationship between SII and clinicopathologic features was investigated. We used Receiver operating characteristic curves to compare the predictive values of NCR between SII and other inflammation indices. Binary logistic analysis was used to identify independent risk factors for NCR. These factors were then used to construct a predictive nomogram. RESULTS: SII was associated with larger tumor size, male gender, older age, submucosal invasion, and a greater risk of NCR. SII showed better predictivity of NCR than platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). SII [odds ratio (OR) = 1.003, P = 0.001], NLR (OR = 1.520, P = 0.029), PLR (OR = 1.009, P = 0.010), upper stomach tumors (OR = 16.393, P < 0.001), poorly differentiated type (OR = 29.754, P < 0.001), ulceration (OR = 4.814, P = 0.001), and submucosal invasion (OR = 48.91, P < 0.001) were independent risk factors for NCR. The nomogram model based on these factors exhibited superior concordance and accuracy. CONCLUSION: SII could be considered a simple and effective predictor of NCR of ESD in EGC patients.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Humanos , Masculino , Mucosa Gástrica/patologia , Inflamação/patologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Feminino
17.
Small ; 19(16): e2207409, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36683211

RESUMO

Elastomers are regarded as one of the best candidates for the matrix material of soft electronics, yet they are susceptible to fracture due to the inevitable flaws generated during applications. Introducing microstructures, sacrificial bonds, and sliding cross-linking has been recognized as an effective way to improve the flaw insensitivity rate (Rinsen ). However, these elastomers still prone to failure under tensile loads with the presence of even small flaws. Here, this work reports a polybutadiene elastomer with unprecedented Rinsen via the synergy of hydrogen bond and entanglement. The resulting polybutadiene elastomer exhibits a Rinsen  ≈1.075, which is much higher than those of reported elastomers. By molecular chain interaction and molecular chain conformation analysis, this work demonstrates that the synergistic effect of hydrogen bond dissociation and entanglement slip in the polybutadiene elastomers during stretching leads to the high Rinsen . Using polybutadiene elastomer as matrix of thermal interface materials, this work demonstrates effective heat transfer for strain sensor and electronic devices. In addition, cytocompatibility of the elastomers is verified by cell proliferation and live/dead viability assays. The combination of outstanding biocompatible and excellent mechanical properties of the elastomers creates new opportunities for their applications in electronic skin.

18.
Mater Horiz ; 10(3): 928-937, 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36597840

RESUMO

Most elastomers suffer from poor thermal conductivity, which limits their further applications in various fields, especially for electronic devices. A common method to enhance thermal conductivity is to introduce thermally conductive fillers into elastomers. Unfortunately, thermal conductivity and compliance are often correlated and coupled: large amounts of fillers are required to increase thermal conductivity while damaging the compliance dramatically. In this study, we report thermally conductive and compliant polyurethane elastomer composites by constructing a tri-branched polymer network. The resultant polyurethane elastomer composites exhibit excellent superhigh stretchability (2000%), low Young's modulus (640 kPa), and low thermal resistance (0.11 K cm2 W-1). Experimental rheology and a theoretical tube model are employed to study the nature of the high compliant tri-branched polymer network. Furthermore, the remarkable flexibility of our elastomer composite and heat dissipation act as thermal interface materials in the thermal management of flexible electronics. These findings advance our understanding on the rational design of the polymer frameworks of thermal composites, improving our ability to predict, design, and leverage their unique properties for future applications.

19.
Acta Biomater ; 157: 538-550, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36494007

RESUMO

Most photosensitizer molecules used for the photodynamic therapy (PDT) are chemically-synthesized organic photosensitizer dyes which show several limitations such as unsatisfactory cell uptake, weak selectivity and off-target phototoxicity. Recently, genetically-encoded photosensitizers have attracted increasing attentions which provide the targeted cell elimination with single-cell precision. However, their applications are mainly limited by the shallow tissue penetration depth of the excitation light and the low cell apoptosis ratio. Herein, we developed a feasible upconversion nanoparticle (UCNP)-based optogenetic nanosystem with three-in-one functional integration: bio-imaging, NIR-triggered PDT and cascade gene therapy. Firstly, the mitochondria-targeted genetically-encoded photosensitizer was constructed and transfected into cancer cells. Then, the functional upconversion nanoprobe was constructed with the mitochondria targetability and then the siRNA was loaded on the surface of UCNPs via the reactive oxygen species (ROSs) sensitive chemical bond. After the transfection and incubation, both of the upconversion nanoprobe and the genetically-encoded photosensitizer were accumulated in the mitochondria of cancer cells. Under the NIR irradiation, the emission of UCNPs could excite the expressed protein photosensitizer to generate ROSs which then stimulated the release of siRNAs in a controllable manner, achieving PDT and cascade gene therapy. Since the generation of ROSs and the release of siRNA occurred in the mitochondria in-situ, the mitochondria-mediated cell apoptosis signal pathway would be activated to induce cell apoptosis and subsequently inhibit tumor growth. To the best of our knowledge, this is the first report about NIR laser-activated, organelle-localized genetically-encoded photosensitizers developed for cascade therapy, which will widen the application of optogenetic tools in the tumor therapy. STATEMENT OF SIGNIFICANCE: The application of genetically-encoded photosensitizers in photodynamic therapy (PDT) is mainly limited by the shallow tissue penetration depth of the excitation light and unsatisfactory therapeutic performance. In this experiment, we developed an upconversion nanoparticles-based optogenetic nanosystem to enhance the PDT and cascade gene therapy for malignant tumors. The expressed genetically-encoded photosensitizers were accumulated in the mitochondria, which were activated in situ by the upconversion nanoprobe. Besides, the photogenerated reactive oxygen species (ROSs) stimulated the release of siRNAs in a controllable manner. To the best of our knowledge, this is the first report about NIR laser-activated, genetically-encoded photosensitizers developed for organelle-localized controllable cascade therapy. We hope this work can accelerate the application of genetically-encoded photosensitizers in the tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Optogenética , Nanopartículas/química , Neoplasias/tratamento farmacológico , Terapia Genética , RNA Interferente Pequeno/uso terapêutico , Linhagem Celular Tumoral
20.
ACS Sens ; 7(12): 3611-3633, 2022 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-36455009

RESUMO

Acoustic-based imaging techniques, including ultrasonography and photoacoustic imaging, are powerful noninvasive approaches for tumor imaging owing to sound transmission facilitation, deep tissue penetration, and high spatiotemporal resolution. Usually, imaging modes were classified into "always-on" mode and "activatable" mode. Conventional "always-on" acoustic-based probes often have difficulty distinguishing lesion regions of interest from surrounding healthy tissues due to poor target-to-background signal ratios. As compared, activatable probes have attracted attention with improved sensitivity, which can boost or amplify imaging signals only in response to specific biomolecular recognition or interactions. The tumor microenvironment (TME) exhibits abnormal physiological conditions that can be used to identify tumor sections from normal tissues. Various types of organic dyes and biomaterials can react with TME, leading to obvious changes in their optical properties. The TME also affects the self-assembly or aggregation state of nanoparticles, which can be used to design activatable imaging probes. Moreover, acoustic-based imaging probes and therapeutic agents can be coencapsulated into one nanocarrier to develop nanotheranostic probes, achieving tumor imaging and cooperative therapy. Satisfactorily, ultrasound waves not only accelerate the release of encapsulated therapeutic agents but also activate therapeutic agents to exert or enhance their therapeutic performance. Meanwhile, various photoacoustic probes can convert photon energy into heat under irradiation, achieving photoacoustic imaging and cooperative photothermal therapy. In this review, we focus on the recently developed TME-triggered ultrasound and photoacoustic theranostic probes for precise tumor imaging and targeted tumor therapy.


Assuntos
Neoplasias , Fototerapia , Humanos , Fototerapia/métodos , Medicina de Precisão , Microambiente Tumoral , Nanomedicina Teranóstica/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Acústica
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