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1.
Acta Biomater ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38849021

RESUMO

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. STATEMENT OF SIGNIFICANCE: The advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.

2.
Adv Healthc Mater ; : e2400943, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856967

RESUMO

Cancer cells support their uncontrolled proliferation primarily by regulating energy metabolism. Inhibiting tumor growth by blocking the supply of nutrients is an effective treatment strategy. Fasting-mimicking diet (FMD), as a low-calorie, low-protein, low-sugar, high-fat diet, can effectively reduce the nutrient supply to tumor cells. However, the significant biological barrier presented by the tumor microenvironment imposes greater demands and challenges for drug design. This study constructs the multifunctional nanocomposite ZnFe2O4@TiO2@CHC@Orl-FA (ZTCOF), which has great potential to overcome the aforementioned drawbacks. ZnFe2O4@TiO2 could produce 1O2 with ultrasound, and stimulate the Fenton-like conversion of endogenous H2O2 to ·OH, achieving a combined therapeutic effect of sonodynamic therapy (SDT) and chemodynamic therapy (CDT). Orl (Orlistat) and CHC (α-cyano-4-hydroxycinnamic acid) not only block tumor cell energy metabolism but also increase sensitivity to reactive oxygen species, enhancing the cytotoxic effect on tumor cells. Furthermore, combining the treatment strategies with FMD condition control can further inhibit cancer cell energy metabolism, achieving significant synergistic anti-tumor therapy. Both in vitro and in vivo experiments confirm that ZTCOF with SDT/CDT/starvation can achieve effective tumor suppression and destruction. This work provides theoretical and technical support for anti-tumor multimodal synergistic therapy.

3.
J Control Release ; 370: 438-452, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38701885

RESUMO

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an "active" state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the "immunosilent" TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a "reactive oxygen species (ROS) storm". Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.


Assuntos
Clorofilídeos , Cobre , Imunoterapia , Camundongos Endogâmicos BALB C , Porfirinas , Piroptose , Espécies Reativas de Oxigênio , Microambiente Tumoral , Piroptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Porfirinas/administração & dosagem , Imunoterapia/métodos , Animais , Cobre/administração & dosagem , Linhagem Celular Tumoral , Humanos , Feminino , Terapia por Ultrassom/métodos , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Camundongos
4.
ACS Appl Mater Interfaces ; 16(20): 26590-26603, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38742307

RESUMO

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) has been widely used in the treatment of a variety of tumors. Compared with other therapeutic methods, this treatment has the advantages of high efficiency, strong penetration, and controllable treatment range. PDT kills tumors by generating a large amount of reactive oxygen species (ROS), which causes oxidative stress in the tumor. However, this killing effect is significantly inhibited by the tumor's own resistance to ROS. This is because tumors can either deplete ROS by high concentration of glutathione (GSH) or stimulate autophagy to eliminate ROS-generated damage. Furthermore, the tumor can also consume ROS through the lactic acid metabolic pathway, ultimately hindering therapeutic progress. To address this conundrum, we developed a UCNP-based nanocomposite for enhanced PDT by reducing tumor ROS resistance. First, Ce6-doped SiO2 encapsulated UCNPs to ensure the efficient energy transfer between UCNPs and Ce6. Then, the biodegradable tetrasulfide bond-bridged mesoporous organosilicon (MON) was coated on the outer layer to load chloroquine (CQ) and α-cyano4-hydroxycinnamic acid (CHCA). Finally, hyaluronic acid was utilized to modify the nanomaterials to realize an active-targeting ability. The obtained final product was abbreviated as UCNPs@MON@CQ/CHCA@HA. Under 980 nm laser irradiation, upconverted red light from UCNPs excited Ce6 to produce a large amount of singlet oxygen (1O2), thus achieving efficient PDT. The loaded CQ and CHCA in MON achieved multichannel enhancement of PDT. Specifically, CQ blocked the autophagy process of tumor cells, and CHCA inhibited the uptake of lactic acid by tumor cells. In addition, the coated MON consumed a high level of intracellular GSH. In this way, these three functions complemented each other, just as the "three musketeers" punctured ROS resistance in tumors from multiple angles, and both in vitro and in vivo experiments had demonstrated the elevated PDT efficacy of nanomaterials.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Animais , Humanos , Camundongos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/metabolismo , Dióxido de Silício/química , Cloroquina/farmacologia , Cloroquina/química , Camundongos Endogâmicos BALB C
5.
Int J Nanomedicine ; 19: 3555-3575, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38638364

RESUMO

Background: Neutrophils rapidly accumulate in large numbers at sites of tissue damage, exhibiting not only their well-known bactericidal capabilities but also playing crucial roles in angiogenesis and tissue repair. While exosomes derived from human umbilical cord mesenchymal stem cells (HucMSC-Exo) have emerged as a promising therapeutic tool, their exact mechanisms of action remain partly elusive. We hypothesize that HucMSC-Exo treatment may modulate neutrophil phenotypes, thereby significantly influencing wound healing outcomes. Methods: HucMSC-Exo were isolated via ultracentrifugation and subsequently administered through subcutaneous injection into full-thickness cutaneous wounds in mice. To determine the impact of host neutrophils on the healing effects of HucMSC-Exo in skin injuries, strategies including neutrophil depletion and adoptive transfer were employed. Flow cytometry was used to evaluate the proportion of N2 subtype neutrophils in both normal and diabetic wounds, and the effect of HucMSC-Exo on this proportion was assessed. Furthermore, the mitochondrial metabolic reprogramming driven by HucMSC-Exo during N2 polarization was investigated through JC1 staining, ATP quantification, fatty acid uptake assays, and assessment of FAO-related genes (Cpt1b, Acadm, and Acadl). Results: Depleting host neutrophils strikingly dampened prohealing effect of HucMSC-Exo on skin injury, while adoptive transfer of bone marrow neutrophils rescued this process. During normal healing process, some neutrophils expressed N2 markers, in contrast, diabetic wounds exhibited a reduced expression of N2 markers. After treatment with HucMSC-Exo, most neutrophils increased the phosphorylation of STAT6, leading to mitochondrial metabolic reprogramming and thus acquired an N2 phenotype. These N2 neutrophils, polarized by HucMSC-Exo, boosted the release of proangiogenic factors, particularly BV8, a myeloid cell-derived proangiogenic factor, and induced angiogenesis thereby favoring tissue restoration. Conclusion: This research uniquely demonstrates the identification of N2 neutrophils in skin injury and shows that HucMSC-Exo could skew neutrophils toward N2 phenotype, enhancing our insight into how cells react to HucMSC-Exo.


Assuntos
Diabetes Mellitus , Exossomos , Células-Tronco Mesenquimais , Camundongos , Humanos , Animais , Neutrófilos , Angiogênese , Cicatrização , Células-Tronco Mesenquimais/metabolismo , Diabetes Mellitus/metabolismo , Exossomos/metabolismo , Cordão Umbilical
6.
Adv Healthc Mater ; 13(4): e2302095, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37975590

RESUMO

Pyroptosis, as an inflammatory cell death, has been widely applied in tumor therapy, but its systemic adverse reactions caused by nonspecific activation still seriously hinder its application. Herein, a near-infrared (NIR) light-triggered thermoresponsive pyroptosis strategy is designed for on-demand initiation of pyroptosis and synergistic tumor immunotherapy. Specifically, glucose oxidase (GOx) loaded and heat-sensitive material p(OEOMA-co-MEMA) (PCM) modified mesoporous Pt nanoparticles (abbreviated as PCM Pt/GOx) are prepared as the mild-temperature triggered pyroptosis inducer. Pt nanoparticles can not only serve as nanozyme with catalase-like activity to promote GOx catalytic reaction, but also act as photothermal agent to achieve mild-temperature photothermal therapy (PTT) and thermoresponsive GOx release on-demand under the irradiation of NIR light, thereby activating and promoting pyroptosis. In vitro and in vivo experiments prove that NIR light-triggered thermoresponsive pyroptosis system exhibits excellent antitumor immunity activity as well as significantly inhibits tumor growth. The precise control of pyroptosis by NIR light as well as pyroptosis cooperated with mild-temperature PTT for synergistically attenuated tumor immunotherapy are reported for the first time. This work provides a new method to initiate pyroptosis on demand, which is of great significance for spatiotemporally controllable pyroptosis and immunotherapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Piroptose , Raios Infravermelhos , Neoplasias/terapia , Imunoterapia , Linhagem Celular Tumoral , Fototerapia , Microambiente Tumoral
7.
Small Methods ; 8(3): e2300945, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37906051

RESUMO

Traditionally referred to as "metabolic junk", lactate has now been recognized as essential "energy currency" and crucial "messenger" that contributes to tumor evolution, immunosuppression, etc., thus presenting a promising strategy for antitumor interventions. Similarly, kynurenine (Kyn) also exerts an immunosuppressive function, thereby significantly compromising the effectiveness of immunotherapy. This study proposes and validates a strategy for enhancing immunotherapy through photothermal-assisted depletion of lactate sustained by cycle-like O2 supply, with blocking the tryptophan (Trp)/Kyn metabolic pathway. In brief, a nanozyme therapeutic agent (PNDPL) is constructed, which mainly consists of PtBi nanozymes, lactate oxidase (LOX) and the indoleamine 2,3-dioxygenase (IDO) inhibitor NLG919. The PtBi nanozymes, which exhibit a catalase (CAT)-like activity, form a positive feedback loop with LOX to consume lactate while self-supplying O2 . Moreover, PtBi nanozymes retain enzyme-like performance even in a slightly acidic tumor microenvironment. Under 1064 nm irradiation, photothermal therapy (PTT) not only induces tumor cell death but also accelerates lactate exhaustion. Therefore, the combination of lactate depletion-induced starvation therapy and PTT, along with the blocking of IDO-mediated immune escape, effectively inhibits tumor growth and reverses immunosuppressive microenvironment, thus preventing tumor metastasis. This study represents the first investigation into the synergistic antitumor effects by lactate metabolism regulation and IDO-related immunotherapy.


Assuntos
Cinurenina , Neoplasias , Humanos , Cinurenina/metabolismo , Ácido Láctico/farmacologia , Triptofano/farmacologia , Imunoterapia , Neoplasias/terapia , Microambiente Tumoral
8.
Small Methods ; : e2301231, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126694

RESUMO

Despite significant breakthroughs in immunotherapy, the limitations of inadequate immune stimulation and stubborn immune resistance continue to present opportunities and challenges. Therefore, a two-pronged approach, encompassing the activation of immunogenic cell death (ICD) and blocking the indoleamine 2,3-dioxygenase (IDO)-mediated pathway, is devised to elicit systemic anti-tumor immunity and alleviate immunosuppression. Herein, a tumor microenvironment (TME)-specific driven nanoagent is composed of a tetrasulfide bond-bridged mesoporous silica layer (MON) coated up-conversion nanoparticles as a nano-carrier, combines Fe2+ , curcumin, and indoximod for operating chemodynamic therapy/chemotherapy/immunotherapy. The consumption of glutathione (GSH) caused by MON degradation, the Fenton reaction of Fe2+ , and curcumin triggering mitochondrial damage collectively exacerbate the oxidative stress, leading to a violent immunoreaction and reversal of the immunosuppressive TME through a combination of IDO-inhibitors. Meanwhile, upconversion luminescence (UCL) imaging serves as a significant guiding tool for drug delivery and the treatment of nanoagents. In vivo and in vitro experiment results demonstrate that the nanosystem not only effectively inhibits the growth of primary tumors but also induces immune priming and memory effects to reject re-challenged tumors. The strategy as a complementary approach displays great potential for future immunotherapy along with other multimodal treatment modes.

9.
Heliyon ; 9(11): e21332, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37964821

RESUMO

Photoacoustic imaging is a good method for biological imaging, for this purpose, materials with strong near infrared (NIR) absorbance are required. In the present study, machine learning models are used to predict the light absorption behavior of polymers. Molecular descriptors are utilized to train a variety of machine learning models. Building blocks are searched from chemical databases, as well as new building blocks are designed using chemical library enumeration method. The Breaking Retrosynthetically Interesting Chemical Substructures (BRICS) method is employed for the creation of 10,000 novel polymers. These polymers are designed based on the input of searched and selected building blocks. To enhance the process, the optimal machine learning model is utilized to predict the UV/visible absorption maxima of the newly designed polymers. Concurrently, chemical similarity analysis is also performed on the selected polymers, and synthetic accessibility of selected polymers is calculated. In summary, the polymers are all easy to synthesize, increasing their potential for practical applications.

11.
Adv Healthc Mater ; 12(32): e2301728, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37602576

RESUMO

Notwithstanding that immunotherapy has made eminent clinical breakthroughs, activating the immunogenicity and breaking the immunosuppressive tumor microenvironment (ITME) remains tempting yet challenging. Herein, a customized-designed immunostimulant is engineered for attenuating ITME and eliciting an immune response to address this challenge head-on. This immunostimulant is equipped with dual silica layers coated upconversion nanoparticles (UCNPs) as nanocarriers modified with endoplasmic reticulum (ER)-targeted molecular N-p-Tosylglycine, in which the dense silica for chlorin e6 (Ce6) and the glutathione (GSH)-responsive degradable silica for loading resveratrol (RES) - (UCSMRER ). On the one hand, this precise ER-targeted photodynamic therapy (PDT) can generate reactive oxygen species (ROS) in situ under the 980 nm laser irradiation, which not only induced severe cell death directly but also caused intense ER stress-based immunogenic cell death (ICD). On the other hand, tumor hypoxia aggravated by the PDT is alleviated by RES released on-demand, which reduced oxygen consumption by impairing the mitochondrial electron transport chain (ETC). This integrated precise ER-targeted and oxygen-compensated strategy maximized the PDT effect and potentiated ICD-associated immunotherapy, which availed to attenuate ITME, activate tumor immunogenicity, and further magnify the anti-tumor effect. This innovative concept about PDT and immunotherapy sheds light on cancer-related clinical application.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Oxigênio , Linhagem Celular Tumoral , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/uso terapêutico , Nanopartículas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício , Retículo Endoplasmático/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia
12.
Nanoscale ; 15(33): 13617-13627, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37575088

RESUMO

The emergence of multidrug-resistant (MDR) bacterial infections calls for novel strategies for effective bacterial inhibition and wound healing. Phototherapeutic approaches are promising in treating bacterial infection because of their high efficiency, noninvasiveness, and few side effects; however, their antibacterial effect is limited by the formation of biofilms in wounds. Herein, we report novel composite nanoparticles (mPt/ICG-αA NPs) combining mesoporous platinum (mPt) nanoparticles, indocyanine green (ICG) and α-amylase (αA) for combating MDR bacteria and treating wound infection, which integrates a triple bacterial inhibition mechanism arising from the combination of photodynamic therapy (PDT), photothermal therapy (PTT) and α-amylase enzymatic activities. The combination of mPt and ICG significantly enhances the effect of PTT and the temperature can be increased up to 80.8 °C to induce efficacious bacterial degeneration. Meanwhile, mPt/ICG-αA (mPIA) NPs with a low concentration of 25 µg mL-1 exhibited a remarkable catalase activity (CAT) and could continuously decompose endogenous H2O2 into O2 in a hypoxic microenvironment, thereby enhancing the PDT effect to achieve broad-spectrum bactericidal activity. mPIA NPs showed excellent MDR antibacterial efficiency against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and the bactericidal rate reached up to 99.0% and 97.2% with single 808 nm near-infrared light irradiation, respectively. mPIA NPs also exhibited an excellent ability to destroy biofilms and biocompatibility. Animal experiments further suggested that mPIA NPs could achieve the successful repairment of wounds infected with S. aureus in living systems, while this platform demonstrated negligible toxicity towards mice. Considering the superior performances of mPIA NPs, the synergistic αA-CAT-PDT-PTT boosted therapeutic activity presented in the current work provides a promising method to effectively fight against biofilm-related infectious diseases and wound healing.


Assuntos
Verde de Indocianina , Nanopartículas , Camundongos , Animais , Verde de Indocianina/farmacologia , Platina/farmacologia , Escherichia coli , Staphylococcus aureus , alfa-Amilases , Peróxido de Hidrogênio , Nanopartículas/uso terapêutico , Cicatrização , Antibacterianos/farmacologia
13.
Small ; 19(44): e2303596, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37394715

RESUMO

Breaking immunosuppressive tumor microenvironment (TME) has unique effects on inhibiting tumor growth and recurrence. Here, an endoplasmic reticulum (ER) targeted PdPtCu nanozyme (PNBCTER ) is prepared to boost immunotherapy. First, PNBCTER has three kinds of enzyme activities, including catalase (CAT), glutathione oxidase (GSHOx), and peroxidase (POD)-like activities, which can reshape the TME. Second, PNBCTER kills tumor cells by photodynamic therapy (PDT) and photothermal therapy (PTT). Third, guided by TER , PNBCTER not only realizes the combination therapy of PDT, PTT and chemodynamic therapy (CDT), but also damages the ER of tumor cells and actives antitumor immune response, which breaks through the immune blockade of TME. Finally, the NLG919 blocks the tryptophan/kynurenine immune escape pathway and reverses the immunosuppressive TME. The strategy that reshaping the TME by enzyme catalysis and breaking immunosuppression provides a novel way for the application of combination therapy in tumor.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Imunoterapia , Estresse do Retículo Endoplasmático , Catálise , Terapia Combinada , Linhagem Celular Tumoral
14.
Front Oncol ; 13: 1117622, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37182154

RESUMO

Background: Hypopharyngeal squamous cell cancer (HSCC) is one of the most malignant tumors of the head and neck. It is not easy to detect in the early stage due to its hidden location; thus, lymph node metastasis is highly likely at diagnosis, leading to a poor prognosis. It is believed that epigenetic modification is related to cancer invasion and metastasis. However, the role of m6A-related lncRNA in the tumor microenvironment (TME) of HSCC remains unclear. Methods: The whole transcriptome and methylation sequencing of 5 pairs of HSCC tissues and adjacent tissues were performed to identify the methylation and transcriptome profiles of lncRNAs. The biological significance of lncRNAs differentially expressing the m6A peak was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. By constructing an m6A lncRNA-microRNA network, the mechanism of m6A lncRNAs in HSCC was analyzed. The relative expression levels of selected lncRNAs were examined by quantitative polymerase chain reaction. The CIBERSORT algorithm was used to evaluate the relative proportion of immune cell infiltration in HSCC and paracancerous tissues. Results: Based on an in-depth analysis of the sequencing results, 14413 differentially expressed lncRNAs were revealed, including 7329 up-regulated and 7084 down-regulated lncRNAs. Additionally, 4542 up-methylated and 2253 down-methylated lncRNAs were detected. We demonstrated methylation patterns and gene expression profiles of lncRNAs of HSCC transcriptome. In the intersection analysis of lncRNAs and methylated lncRNAs, 51 lncRNAs with up-regulated transcriptome and methylation and 40 lncRNAs with down-regulated transcriptome and methylation were screened, and significantly differentiated lncRNAs were further studied. In the immune cell infiltration analysis, B cell memory was significantly elevated in cancer tissue, while γδT cell amount was significantly decreased. Conclusion: m6A modification of lncRNAs might be involved in HSCC pathogenesis. Infiltration of immune cells in HSCC might provide a new direction for its treatment. This study provides new insights for exploring the possible HSCC pathogenesis and searching for new potential therapeutic targets.

15.
Inorg Chem ; 61(18): 6852-6860, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35477242

RESUMO

Combined photothermal/photodynamic therapy is a promising strategy to achieve an enhanced anticancer effect. However, hypoxia is one of the representative characteristics of the microenvironment of solid tumors, which not only attenuates the therapeutic effects but also promotes tumor invasion and metastasis. Herein, a PtBi-ß-CD-Ce6 nanoplatform for the generation of sustained O2 was constructed for more effective tumor therapy. In detail, the catalase (CAT)-like nanozyme, PtBi, which could decompose H2O2 to produce O2, was modified with ß-cyclodextrin (ß-CD). O2 would be converted into 1O2 by PtBi-ß-CD-Ce6 for enhanced photodynamic therapy (PDT) under 650 nm laser irradiation. In addition, by reason of excellent absorption in the near-infrared-II (NIR-II) region, PtBi-ß-CD-Ce6 was used for photoacoustic imaging (PA) and photothermal imaging (PT)-guided photothermal therapy (PTT) in the NIR-II biowindow. Furthermore, PtBi-ß-CD-Ce6 could be elected to serve as a contrast agent for X-ray computed tomography (CT) imaging due to the apparent X-ray attenuation capability of the Pt and Bi elements themselves. Therefore, by integrating the advantages of overcoming the hypoxia function and photothermal effect into a single nanoplatform, PtBi-ß-CD-Ce6 showed an immense possibility in multimodal imaging-guided combined PDT/PTT.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , beta-Ciclodextrinas , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio , Hipóxia/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Microambiente Tumoral , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/uso terapêutico
16.
RSC Adv ; 12(9): 5595-5611, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35425539

RESUMO

In order to study the photoelectric properties of the adsorption of different metal atoms on a two-dimensional (2D) perovskite surface, in this article, we built many models of Ag, Au, and Bi atoms adsorbed on 2D perovskite. We studied the rules influencing 2D perovskite adsorbing metal atoms with different n values (the n value is the number of inorganic layers of 2D perovskite; here n = 1, 2, and 3). Based on n = 2 2D perovskite, we successively used Ag, Au, and Bi metal atoms to adsorb on the 2D perovskite surface. Firstly, we calculated their adsorption energies. Based on the lowest energy principle, we found that Bi atom adsorption on the 2D perovskite surface gave the most stable structure among the three metal adsorptions because the energy of the Bi adsorption system was the smallest. Secondly, the electron transport process takes place from the s to the p orbital when Au and Ag atoms adsorb on the 2D perovskite surface, but in the Bi atom adsorption, the electron transport process takes place from the p to the p orbital, because the p-p orbital transport energy is lower than that of the s-p orbital. Therefore, Bi atom adsorption on the 2D perovskite surface can improve charge carrier transfer. Thirdly, we calculated the bond angles and bond energies of different metal adsorptions on 2D perovskite. Bi adsorption has greater interaction with the surface atoms of 2D perovskite than Ag or Au atom adsorption, which effectively enhances the surface polarization effects, and enhances the photoelectric properties of 2D perovskite. The light absorption spectrum further confirms that Bi atom adsorption has a greater impact on the 2D perovskite than the action of Ag or Au adsorption. Finally, in an experiment, we fabricated a 2D perovskite solar cell with an ITO/PEDOT:PSS/2D perovskite/PEI/Ag (Au, Bi) structure. The Bi electrode solar cell achieves the highest photoelectric conversion efficiency (PCE) of 15.16% among the three cells with forward scanning, which is consistent with the theoretical analysis. We believe that the adsorption of metals like Bi on a 2D perovskite surface as an electrode is conducive to improving the charge transport performance.

18.
Genomics ; 114(1): 31-37, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34843904

RESUMO

Evidence has suggested the potential of tumor-educated platelets as a biomarker trove for cancer diagnostics, but the difficulty in isolation limits its application. Since most of the circulating RNAs are derived from platelets, the change of RNA profile in platelets may lead to altered RNA expression in serum. Here, we identified a panel of platelet-associated long non-coding RNAs (lncRNAs) and evaluated its diagnostic capacity in serum of colorectal cancer (CRC) patients. Four lncRNAs, LNCAROD, SNHG20, LINC00534, and TSPOAP-AS1, were upregulated in both platelets and serum of CRC patients. A binary logistic model derived from them has validated area under roc curve of 0.78 indicating great performance. Furthermore, the expression levels of LNCAROD and TSPOAP-AS1 were correlated with cancer staging and tumor location. Together, our results add novel lncRNA biomarkers to the list of blood tests for CRC diagnostics and provide molecular evidence for the cross-talk between CRC platelets and serum.


Assuntos
Ácidos Nucleicos Livres , Neoplasias Colorretais , RNA Longo não Codificante , Biomarcadores , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Longo não Codificante/genética , Curva ROC
19.
Adv Sci (Weinh) ; 8(12): 2004510, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34194931

RESUMO

In this article, two different types of spacer cations, 1,4-butanediamonium (BDA2+) and 2-phenylethylammonium (PEA+) are co-used to prepare the perovskite precursor solutions with the formula of (BDA)1- a (PEA2) a MA4Pb5X16. By simply mixing the two spacer cations, the self-assembled polycrystalline films of (BDA)0.8(PEA2)0.2MA4Pb5X16 are obtained, and BDA2+ is located in the crystal grains and PEA+ is distributed on the surface. The films display a small exciton binding energy, uniformly distributed quantum wells and improved carrier transport. Besides, utilizing mixed spacer cations also induces better crystallinity and vertical orientation of 2D perovskite (BDA)0.8(PEA2)0.2MA4Pb5X16 films. Thus, a power conversion efficiency (PCE) of 17.21% is achieved in the optimized perovskite solar cells with the device structure of ITO/PEDOT:PSS/Perovskite/PCBM/BCP/Ag. In addition, the complementary humidity and thermal stability are obtained, which are ascribed to the enhanced interlayer interaction by BDA2+ and improved moisture resistance by the hydrophobic group of PEA+. The encapsulated devices are retained over 95% or 75% of the initial efficiency after storing 500 h in ambient air under 40 ± 5% relative humidity or 100 h in nitrogen at 60 °C.

20.
Opt Express ; 29(2): 2162-2171, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33726417

RESUMO

Measurement of high dynamic range objects is an obstacle in structured light 3D measurement. They entail both over-exposed and low-exposed pixels in a single exposure. This paper proposed a polarization-enhanced fringe pattern (PEFP) method that a high dynamic range image can be obtained within a single exposure time. The degree of linear polarization (DOLP) is calculated using the polarization properties of reflected light and a linear polarizer in fixed azimuth in this method. The DOLP is efficiently estimated by the projected polarization-state-encode (PSE) pattern, and it does not need to change the state of the polarizer. The DOLP depends on light intensity rather than the reflectivity of the object surfaces indicated in experimental results. The contrast of fringe patterns was enhanced, and the quality of fringe patterns was improved by the proposed method. More sufficient 3D point clouds and high-quality shape can be recovered using this method.

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