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1.
Artigo em Inglês | MEDLINE | ID: mdl-38870511

RESUMO

Objective: This work investigated the clinical intervention effect of evidence-based nursing (EBN) measures for patients in the recovery stage after general anesthesia (GA), aiming to provide a nursing reference for patients in the recovery stage after surgery. Methods: The enrolled participants were 102 patients who underwent surgical treatment in our hospital from December 2021 to December 2022. According to the principle of randomized control, they were enrolled into an observation group (51 cases, Obs group) and a control group (51, cases, Ctrl group), and the general nursing methods and EBN measures were respectively implemented. The incidence of restlessness, complication rate, and nursing satisfaction were compared among patients. The recovery period and visual analog scale (VAS) were evaluated. Results: The eye-opening time, palm-holding time, and extubation time in the Obs group were shorter than those in the Ctrl group (P < .05). The incidence of agitation during convalescence under GA in the Obs group was significantly lower than in the Ctrl group, with a statistically significant difference among both groups (P < .05). Compared to the Ctrl group, the VAS score of patients in the Obs group receiving the EBN was lower at 6 h, 12 h, and 24 h after the surgery (P < .05). The patients in the Obs group presented a substantially lower complication rate and remarkably higher nursing satisfaction (P < .05). Conclusion: The application of EBN measures in patients after GA could effectively shorten the recovery time, lower the incidence of agitation and complication rate during the recovery, and improve nursing satisfaction.

2.
BMC Cancer ; 24(1): 420, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580922

RESUMO

BACKGROUND: Clear cell carcinoma of the kidney is a common urological malignancy characterized by poor patient prognosis and treatment outcomes. Modulation of vasculogenic mimicry in tumor cells alters the tumor microenvironment and the influx of tumor-infiltrating lymphocytes, and the combination of its inducers and immune checkpoint inhibitors plays a synergistic role in enhancing antitumor effects. METHODS: We downloaded the data from renal clear cell carcinoma samples and vasculogenic mimicry-related genes to establish a new vasculogenic mimicry-related index (VMRI) using a machine learning approach. Based on VMRI, patients with renal clear cell carcinoma were divided into high VMRI and low VMRI groups, and patients' prognosis, clinical features, tumor immune microenvironment, chemotherapeutic response, and immunotherapeutic response were systematically analyzed. Finally, the function of CDH5 was explored in renal clear cell carcinoma cells. RESULTS: VMRI can be used for prognostic and immunotherapy efficacy prediction in a variety of cancers, which consists of four vasculogenic mimicry-related genes (CDH5, MMP9, MAPK1, and MMP13), is a reliable predictor of survival and grade in patients with clear cell carcinoma of the kidney and has been validated in multiple external datasets. We found that the high VMRI group presented higher levels of immune cell infiltration, which was validated by pathological sections. We performed molecular docking prediction of vasculogenic mimicry core target proteins and identified natural small molecule drugs with the highest affinity for the target protein. Knockdown of CDH5 inhibited the proliferation and migration of renal clear cell carcinoma. CONCLUSIONS: The VMRI identified in this study allows for accurate prognosis assessment of patients with renal clear cell carcinoma and identification of patient populations that will benefit from immunotherapy, providing valuable insights for future precision treatment of patients with renal clear cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Simulação de Acoplamento Molecular , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Prognóstico , Neoplasias Renais/genética , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Imunoterapia , Microambiente Tumoral/genética
3.
Adv Healthc Mater ; 13(13): e2400068, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38320299

RESUMO

Cancer nanovaccines have attracted widespread attention by inducing potent cytotoxic T cell responses to improve immune checkpoint blockade (ICB) therapy, while the lack of co-stimulatory molecules limits their clinical applications. Here, a genetically engineered cancer cytomembrane nanovaccine is reported that simultaneously overexpresses co-stimulatory molecule CD40L and immune checkpoint inhibitor PD1 to elicit robust antitumor immunity for cancer immunotherapy. The CD40L and tumor antigens inherited from cancer cytomembranes effectively stimulate dendritic cell (DC)-mediated immune activation of cytotoxic T cells, while the PD1 on cancer cytomembranes significantly blocks PD1/PD-L1 signaling pathway, synergistically stimulating antitumor immune responses. Benefiting from the targeting ability of cancer cytomembranes, this nanovaccines formula shows an enhanced lymph node trafficking and retention. Compared with original cancer cytomembranes, this genetically engineered nanovaccine induces twofold DC maturation and shows satisfactory precaution efficacy in a breast tumor mouse model. This genetically engineered cytomembrane nanovaccine offers a simple, safe, and robust strategy by incorporating cytomembrane components and co-stimulatory molecules for enhanced cancer immunotherapy.


Assuntos
Vacinas Anticâncer , Células Dendríticas , Imunoterapia , Animais , Imunoterapia/métodos , Camundongos , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Feminino , Humanos , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linhagem Celular Tumoral , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Engenharia Genética/métodos , Nanopartículas/química , Camundongos Endogâmicos BALB C , Linfócitos T Citotóxicos/imunologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Nanovacinas
4.
Int J Biol Macromol ; 254(Pt 1): 127806, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37918593

RESUMO

Bacterial infection and chronic inflammation are two major risks in diabetic wound healing, which increase patient mortality. In this study, a multifunctional sprayable nanogel (Ag-G@CS) based on chitosan has been developed to synergistically inhibit bacterial infection, eradicate biofilm, and relieve inflammation of diabetic wounds. The nanogel is successfully crafted by encapsulating with a nitric oxide (NO) donor and performing in-situ reduction of silver nanoparticles (Ag). The released NO enhances the antibacterial efficacy of Ag, nearly achieving complete eradication of biofilms in vitro. Upon application on both normal or diabetic chronic wounds, the combination effects of released NO and Ag offer a notable antibacterial effect. Furthermore, after bacteria inhibition and biofilm eradication, the NO released by the nanogel orchestrates a transformation of M1 macrophages into M2 macrophages, significantly reducing tumor necrosis factor α (TNF-α) release and relieving inflammation. Remarkably, the released NO also promotes M2a to M2c macrophages, thereby facilitating tissue remodeling in chronic wounds. More importantly, it upregulates the expression of vascular endothelial growth factor (VEGF), further accelerating the wound healing process. Collectively, the formed sprayable nanogel exhibits excellent inhibition of bacterial infections and biofilms, and promotes chronic wound healing via inflammation resolution, which has excellent potential for clinical use in the future.


Assuntos
Infecções Bacterianas , Quitosana , Diabetes Mellitus Experimental , Nanopartículas Metálicas , Animais , Humanos , Quitosana/farmacologia , Óxido Nítrico/farmacologia , Nanogéis , Fator A de Crescimento do Endotélio Vascular/farmacologia , Diabetes Mellitus Experimental/metabolismo , Prata/farmacologia , Cicatrização , Antibacterianos/farmacologia , Macrófagos , Bactérias , Biofilmes , Inflamação
5.
Front Bioeng Biotechnol ; 11: 1225937, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37485315

RESUMO

Introduction: Radiotherapy (RT) is one of the key methods for treating breast cancer. However, the effect of single RT is often poor because of insufficient deposition of X-rays in tumor sites and radiation resistance induced by the abnormal tumor microenvironment (overexpression of glutathione (GSH)). The development of multifunctional RT sensitizers and synergetic therapeutic strategies is, therefore, a promising area for enhancing the anticancer effect of RT. Methods: In this study, a multifunctional nanozyme hydrogel based on Cu-doped polypyrrole (CuP) was designed to work concertedly with a second near-infrared thermal RT. The CuP-based hydrogel (CH) reached the tumor site when injected in-situ and achieved long-term storage. Results: Once stimulated with 1064-nm laser irradiation, the heated and softened hydrogel system released CuP nanozyme to provide photothermal therapy, thereby inhibiting the repair of DNA damage caused by RT. In addition, CuP with dual nanozyme activity depleted the intracellular GSH to reduce the antioxidant capacity of the tumor. Moreover, CuP converted H2O2 to produce ·OH to directly kill the tumor cells, thus enhancing the capability of low-dose RT to inhibit tumor growth. In vivo experiments showed that the CH system used in combination with a low-power 1064-nm laser and low-dose RT (4 Gy) exhibited good synergistic anticancer effects and biological safety. Discussion: As a new light-responsive hydrogel system, CH holds immense potential for radio-sensitization.

6.
ACS Nano ; 17(11): 10206-10217, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37183977

RESUMO

Cuproptosis shows good application prospects in tumor therapy. However, the copper efflux mechanism and highly expressed intracellular reducing substances can inhibit the cuproptosis effects. In this study, a platelet vesicle (PV) coated cuprous oxide nanoparticle (Cu2O)/TBP-2 cuproptosis sensitization system (PTC) was constructed for multiple induction of tumor cuproptosis. PTC was prepared by physical extrusion of AIE photosensitizer (TBP-2), Cu2O, and PV. After the biomimetic modification, PTC can enhance its long-term blood circulation and tumor targeting ability. Subsequently, PTC was rapidly degraded to release copper ions under acid conditions and hydrogen peroxides in tumor cells. Then, under light irradiation, TBP-2 quickly enters the cell membrane and generates hydroxyl radicals to consume glutathione and inhibit copper efflux. Accumulated copper can cause lipoylated protein aggregation and iron-sulfur protein loss, which result in proteotoxic stress and ultimately cuproptosis. PTC treatment can target and induce cuproptosis in tumor cells in vitro and in vivo, significantly inhibit lung metastasis of breast cancer, increase the number of central memory T cells in peripheral blood, and prevent tumor rechallenge. It provides an idea for the design of nanomedicine based on cuproptosis.


Assuntos
Cobre , Neoplasias Cutâneas , Humanos , Cobre/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Biomimética , Apoptose , Melanoma Maligno Cutâneo
7.
Int J Mol Sci ; 24(3)2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36768966

RESUMO

Liposomes, the most widely studied nano-drug carriers in drug delivery, are sphere-shaped vesicles consisting of one or more phospholipid bilayers. Compared with traditional drug delivery systems, liposomes exhibit prominent properties that include targeted delivery, high biocompatibility, biodegradability, easy functionalization, low toxicity, improvements in the sustained release of the drug it carries and improved therapeutic indices. In the wake of the rapid development of nanotechnology, the studies of liposome composition have become increasingly extensive. The molecular diversity of liposome composition, which includes long-circulating PEGylated liposomes, ligand-functionalized liposomes, stimuli-responsive liposomes, and advanced cell membrane-coated biomimetic nanocarriers, endows their drug delivery with unique physiological functions. This review describes the composition, types and preparation methods of liposomes, and discusses their targeting strategies in cancer therapy.


Assuntos
Lipossomos , Neoplasias , Humanos , Lipossomos/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Portadores de Fármacos/uso terapêutico , Nanotecnologia/métodos
8.
Biomaterials ; 295: 122034, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36746049

RESUMO

Radioresistance of Cancer stem cell (CSC) is an important cause of tumor recurrence after radiotherapy (RT). Herein, we designed a type I aggregation-induced emission (AIE) photosensitiser-loaded biomimetic mesoporous organosilicon nanosystem (PMT) for precise depletion of CSC to prevent tumor recurrence after RT. This PMT system is composed of a type I AIE photosensitiser (TBP-2) loaded mesoporous organosilicon nanoparticles (MON) with an outer platelet membrane. The PMT system is able to specifically target CSC. Intracellular glutathione activity leads to MON degradation and the release of TBP-2. Type I photodynamic therapy is activated by exposure to white light, producing a large amount of hydroxyl radicals to promote CSC death. The results of in vivo experiments demonstrated specific removal of CSC following PMT treatment, with no tumor recurrence observed when combined with RT. However, tumor recurrence was observed in mice that received RT only. The expression of CSC markers was significantly reduced following PMT treatment. We demonstrate the development of a system for the precise removal of CSC with good biosafety and high potential for clinical translation. We believe the PMT nanosystem represents a novel idea in the prevention of tumor recurrence.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/metabolismo , Biomimética , Células-Tronco Neoplásicas/patologia , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
9.
Macromol Biosci ; 23(1): e2200329, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36250413

RESUMO

Chemodynamic therapy (CDT) based on Fenton-like reaction is often limited by the tumor microenvironment (TME), which has insufficient hydrogen peroxide, and single CDT treatment is often less efficacious. To overcome these limitations, a hydrogel-based system is designed to enhance the redox stress (EOH) by loading the composite nanomaterial Cu-Hemin-Au, into the agarose hydrogels. The hydrogels can reach the tumor site upon intratumoral injection, and then coagulate and stay for extended period. Once irradiated with near-infrared light, the Cu-Hemin-Au act as a photothermal agent to convert the light energy into heat, and the EOH gradually heated up and softened, releasing the Cu-Hemin-Au residing in it to achieve photothermal therapy (PTT). Benefiting from the glucose oxidase (GOx)-like activity of the Au nanoparticles, glucose in the tumor cells is largely consumed, and hydrogen peroxide (H2 O2 ) is generated in situ, and then Cu-Hemin-Au react with sufficient H2 O2 to generate a large amount of reactive oxygen species, which promote the complete inhibition of tumor growth in mice during the treatment cycle. The hydrogel system for the synergistic enhancement of oxidative stress achieves good PTT/CDT synergy, providing a novel inspiration for the next generation of hydrogels for application in antitumor therapy.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Neoplasias , Animais , Camundongos , Hidrogéis/farmacologia , Ouro , Hemina , Peróxido de Hidrogênio/farmacologia , Microambiente Tumoral , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
10.
Front Bioeng Biotechnol ; 10: 1024089, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246356

RESUMO

Chemodynamic therapy (CDT) is an effective anti-tumor method, while CDT alone cannot achieve a good therapeutic effect. Moreover, the overexpression of glutathione (GSH) in tumor cells dramatically limits the efficiency of CDT. Here, we proposed a hydrogel co-loading SO2 prodrug and FeGA nanoparticles (NPs) for enhancing CDT by photothermal-triggered SO2 gas therapy (FBH) system by mixing benzothiazolyl sulfonates (BTS) and FeGA NPs in a certain ratio and encapsulating them in a heat-sensitive hydrogel. FeGA NPs could accelerate the release of Fe2+ under acidic conditions and light, and combine with excess H2O2 in the tumor for chemokinetic treatment. BTS, as a water-soluble prodrug of SO2, can accurately control the release of SO2 gas by virtue of the excellent photothermal conversion ability of FeGA NPs and the acidic pH value of tumor site. SO2 can not only induce cell apoptosis, but also consume excess GSH in cancer cells and increase the content of reactive oxygen species, which seriously destroyed the redox balance in cancer cells and further promotes the therapeutic effect of Fenton reaction. The intelligent FBH system provided a new approach for the synergistic treatment of CDT and SO2 gas, which demonstrated good anticancer effects both in vivo and in vitro.

11.
Oxid Med Cell Longev ; 2022: 5089857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246405

RESUMO

Single-atom nanozymes (SAZs) with reaction specificity and optimized catalytic properties have great application prospects in tumor therapy. But the complex tumor microenvironment (low content of H2O2) limits its therapeutic effect. In this study, we developed a bionic mesoporous Fe SAZs/DDP nanosystem (CSD) for enhanced nanocatalytic therapy (NCT)/chemotherapy by simultaneously encapsulating the chemotherapeutic drugs cisplatin (DDP) and Fe SAZs with high peroxidase (POD) activity into the cancer cell membrane. CSD could evade immune recognition and actively targets tumor sites, and DDP upregulates endogenous H2O2 levels by activating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, thereby enhancing SAZs-mediated hydroxyl radical (·OH) production, which subsequently leads to mitochondrial damage and intolerance to chemotherapy drug. We used the HGC27/DDP cell line for in vitro and in vivo experiments. The results showed that CSD achieved good therapeutic benefits, without any side effects such as inflammatory reaction. This system can induce multiple antitumor effect with H2O2 self-supply, mitochondrial damage, and ATP downregulation and eventually lead to chemosensitization.


Assuntos
Cisplatino , Neoplasias , Trifosfato de Adenosina , Biomimética , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Peróxido de Hidrogênio , Radical Hidroxila , NADP , NADPH Oxidases/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Peroxidases , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral
12.
Front Bioeng Biotechnol ; 10: 1003777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105600

RESUMO

Chemodynamic therapy (CDT) is a kind of anti-tumor strategy emerging in recent years, but the concentration of hydrogen peroxide (H2O2) in the tumor microenvironment is insufficient, and it is difficult for a single CDT to completely inhibit tumor growth. Here, we designed a CuS nanoparticles (NPs) and camptothecin (CPT) co-loaded thermosensitive injectable hydrogel (SCH) with self-supplied H2O2 for enhanced CDT. SCH is composed of CuS NPs and CPT loaded into agarose hydrogel according to a certain ratio. We injected SCH into the tumor tissue of mice, and under the irradiation of near-infrared region (NIR) laser at 808 nm, CuS NPs converted the NIR laser into heat to realize photothermal therapy (PTT), and at the same time, the agarose hydrogel was changed into a sol state and CPT was released. CPT activates nicotinamide adenine dinucleotide phosphate oxidase, increases the level of H2O2 inside the tumor, and realizes the self-supply of H2O2. At the same time, CuS can accelerate the release of Cu2+ in an acidic environment and light, combined with H2O2 generated by CPT for CDT treatment, and consume glutathione in tumor and generate hydroxyl radical, thus inducing tumor cell apoptosis. The SCH system we constructed achieved an extremely high tumor inhibition rate in vitro and in vivo, presenting a new idea for designing future chemical kinetic systems.

13.
Front Bioeng Biotechnol ; 10: 998571, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110320

RESUMO

Due to its responsiveness to the tumour microenvironment (TME), chemodynamic therapy (CDT) based on the Fenton reaction to produce cytotoxic reactive oxygen species (ROS) to destroy tumor has drawn more interest. However, the Fenton's reaction potential for therapeutic use is constrained by its modest efficacy. Here, we develop a novel injectable hydrogel system (FMH) on the basis of FeGA/MoS2 dual quantum dots (QDs), which uses near-infrared (NIR) laser in order to trigger the synergistic catalysis and photothermal effect of FeGA/MoS2 for improving the efficiency of the Fenton reaction. Mo4+ in MoS2 QDs can accelerate the conversion of Fe3+ to Fe2+, thereby promoting the efficiency of Fenton reaction, and benefiting from the synergistically enhanced CDT/PTT, FMH combined with NIR has achieved good anti-tumour effects in vitro and in vivo experiments. Furthermore, the quantum dots are easily metabolized after treatment because of their ultrasmall size, without causing any side effects. This is the first report to study the co-catalytic effect of MoS2 and Fe3+ at the quantum dot level, as well as obtain a good PTT/CDT synergy, which have implications for future anticancer research.

14.
Nanoscale Adv ; 4(18): 3950-3956, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36133353

RESUMO

Alkyl radicals (R˙), which do not rely on oxygen generation for causing cellular stress, have been applied in tumor treatment, but a large amount of glutathione (GSH) in the tumor cells reacts with alkyl radicals, thereby reducing their antitumor effect. In this study, an enhanced alkyl radical generation system responsive to near-infrared light was designed. The alkyl radical trigger 2,2'-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) and nanozyme pyrite (FeS2) were encapsulated in agarose hydrogel to prepare the AIPH-FeS2-hydrogel (AFH) system. FeS2 can be used as a photothermal agent to convert near-infrared light energy into heat energy, leading to the dissolution of the hydrogel. AIPH is simultaneously induced to produce alkyl radicals. FeS2 can also be used as an oxidative stress amplifier to reduce intracellular GSH content, thereby boosting the therapeutic effect of alkyl radicals. Eventually, the oxygen-independent free radicals generated by the AFH system under near-infrared laser irradiation and photothermal treatment can kill cancer cells through the synergistic oxidation/photothermal effect. The AFH system developed herein provides new insights into enhancing the therapeutic effect of alkyl radicals.

15.
Front Oncol ; 12: 904960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847856

RESUMO

Single photothermal therapy (PTT) has many limitations in tumor treatments. Multifunctional nanomaterials can cooperate with PTT to achieve profound tumor killing performance. Herein, we encapsulated chemotherapeutic drug camptothecin (CPT) and pyrite (FeS2) with dual enzyme activity (glutathione oxidase (GSH-OXD) and peroxidase (POD) activities) into an injectable hydrogel to form a CFH system, which can improve the level of intratumoral oxidative stress, and simultaneously realize FeS2-mediated PTT and nanozymes catalytic treatment. After laser irradiation, the hydrogel gradually heats up and softens under the photothermal agent FeS2. The CPT then released from CFH to tumor microenvironment (TME), thereby enhancing the H2O2 level. As a result, FeS2 can catalyze H2O2 to produce ·OH, and cooperate with high temperature to achieve high-efficiency tumor therapy. It is worth noting that FeS2 can also deplete excess glutathione (GSH) in the cellular level, further amplifying oxidative stress. Both in vivo and in vitro experiments show that our CFH exhibits good tumor-specific cytotoxicity. The CFH we developed provides new insights for tumor treatment.

16.
Front Oncol ; 12: 918416, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847901

RESUMO

Near-infrared (NIR) organic small molecule indocyanine green (ICG) could respond well to 808 nm laser to promote local high temperature and ROS generation for realizing photothermal therapy (PTT)/photodynamic therapy (PDT). However, the high content of GSH in the tumor microenvironment (TME) limited the further therapeutic performance of ICG. Herein, injectable agarose in situ forming NIR-responsive hydrogels (CIH) incorporating Cu-Hemin and ICG were prepared for the first time. When CIH system was located to the tumor tissue through local injection, the ICG in the hydrogel could efficiently convert the light energy emitted by the 808 nm laser into thermal energy, resulting in the heating and softening of the hydrogel matrix, which releases the Cu-Hemin. Then, the over-expressed GSH in the TME could also down-regulated by Cu-Hemin, which amplified ICG-mediated PDT. In vivo experiments validated that ICG-based PDT/PTT and Cu-Hemin-mediated glutathione depletion could eliminate cancer tissues with admirable safety. This hydrogel-based GSH-depletion strategy is instructive to improve the objective response rate of PDT.

17.
Front Oncol ; 12: 888855, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35860592

RESUMO

Sonosensitizer-mediated sonodynamic therapy (SDT) has emerged as a promising anti-tumor strategy. However, this strategy of continuous oxygen consumption further exacerbates the hypoxic tumor microenvironment, which limits its therapeutic efficacy. In this study, we designed a multifunctional hydrogel (PB+Ce6@Hy) that simultaneously co-delivers nanozyme prussian blue (PB) and sonosensitizer chlorin e6 (Ce6) for the realization of photothermal therapy (PTT) and enhanced SDT. When the hydrogel reaches the tumor tissue through local injection, the 808 nm laser can induce the hydrogel to warm up and soften, thereby triggering the release of PB and Ce6. PB can interact with endogenous H2O2 in situ and generate sufficient oxygen to promote the Ce6-mediated SDT effect. Besides, due to the good encapsulation ability of the hydrogel, the nanomaterials can be released in a controlled manner by changing laser parameter, irradiation time, etc. The experimental results show that the PB+Ce6@Hy system we developed can generate a large amount of reactive oxygen species (ROS), which can be combined with the photothermal effect to kill tumor cells, as a result, tumor proliferation has been adequately inhibited. This combined PTT/SDT dynamic strategy provides a new perspective for Ce6-induced cancer therapy, showing great potential for clinical application.

18.
Biosens Bioelectron ; 213: 114425, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35688024

RESUMO

The isolation and analysis of scarce circulating tumor cells (CTCs) with immunomagnetic nanoparticles (IMNs) have shown promising outcomes in noninvasive cancer diagnosis. However, the IMNs adsorb nonspecific proteins after entering into biofluids and the formed protein coronas cover surface targeting ligands, limiting the detection efficiency of IMNs. In addition, the interaction between surface targeting ligands and white blood cells (WBCs) significantly limits the purity of CTCs isolated by IMNs. Furthermore, the interfacial collision of nanoparticles and cells has negative effects on the viability of isolated CTCs. All of these limitations synthetically restrict the isolation and analysis of rare CTCs for early diagnosis and precision medicine. Here, we proposed that surface functionalization of IMNs with neutrophil membranes can simultaneously reduce nonspecific protein adsorption, enhance the interaction with CTCs, reduce the distraction from WBCs, and improve the viability of isolated CTCs. In spiked blood samples, our neutrophil membrane-coated IMNs (Neu-IMNs) exhibited a superior separation efficiency from 41.36% to 96.82% and an improved purity from 40.25% to 90.68% when compared to bare IMNs. Additionally, we successfully isolated CTCs in 19 out of total 20 blood samples from breast cancer patients using Neu-IMNs and further confirmed the feasibility of the isolated CTCs for downstream cell sequencing. Our work provides a new perspective on engineered IMNs for efficient isolation and analysis of CTCs, paving the way for early noninvasive diagnosis of cancer.


Assuntos
Técnicas Biossensoriais , Nanopartículas , Células Neoplásicas Circulantes , Linhagem Celular Tumoral , Separação Celular , Humanos , Separação Imunomagnética , Ligantes , Células Neoplásicas Circulantes/patologia , Neutrófilos/patologia
19.
Eur Radiol ; 32(12): 8692-8705, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35616733

RESUMO

OBJECTIVES: Accurate evaluation of bowel fibrosis in patients with Crohn's disease (CD) remains challenging. Computed tomography enterography (CTE)-based radiomics enables the assessment of bowel fibrosis; however, it has some deficiencies. We aimed to develop and validate a CTE-based deep learning model (DLM) for characterizing bowel fibrosis more efficiently. METHODS: We enrolled 312 bowel segments of 235 CD patients (median age, 33 years old) from three hospitals in this retrospective study. A training cohort and test cohort 1 were recruited from center 1, while test cohort 2 from centers 2 and 3. All patients performed CTE within 3 months before surgery. The histological fibrosis was semi-quantitatively assessed. A DLM was constructed in the training cohort based on a 3D deep convolutional neural network with 10-fold cross-validation, and external independent validation was conducted on the test cohorts. The radiomics model (RM) was developed with 4 selected radiomics features extracted from CTE images by using logistic regression. The evaluation of CTE images was performed by two radiologists. DeLong's test and a non-inferiority test were used to compare the models' performance. RESULTS: DLM distinguished none-mild from moderate-severe bowel fibrosis with an area under the receiver operator characteristic curve (AUC) of 0.828 in the training cohort and 0.811, 0.808, and 0.839 in the total test cohort, test cohorts 1 and 2, respectively. In the total test cohort, DLM achieved better performance than two radiologists (*1 AUC = 0.579, *2 AUC = 0.646; both p < 0.05) and was not inferior to RM (AUC = 0.813, p < 0.05). The total processing time for DLM was much shorter than that of RM (p < 0.001). CONCLUSION: DLM is better than radiologists in diagnosing intestinal fibrosis on CTE in patients with CD and not inferior to RM; furthermore, it is more time-saving compared to RM. KEY POINTS: • Question Could computed tomography enterography (CTE)-based deep learning model (DLM) accurately distinguish intestinal fibrosis severity in patients with Crohn's disease (CD)? • Findings In this cross-sectional study that included 235 patients with CD, DLM achieved better performance than that of two radiologists' interpretation and was not inferior to RM with significant differences and much shorter processing time. • Meaning This DLM may accurately distinguish the degree of intestinal fibrosis in patients with CD and guide gastroenterologists to formulate individualized treatment strategies for those with bowel strictures.


Assuntos
Doença de Crohn , Aprendizado Profundo , Humanos , Adulto , Doença de Crohn/patologia , Intestino Delgado/patologia , Estudos Retrospectivos , Estudos Transversais , Tomografia Computadorizada por Raios X/métodos , Fibrose , Radiologistas
20.
Biomark Res ; 9(1): 85, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34798902

RESUMO

Histopathological examination (biopsy) is the "gold standard" for the diagnosis of colorectal cancer (CRC). However, biopsy is an invasive method, and due to the temporal and spatial heterogeneity of the tumor, a single biopsy cannot reveal the comprehensive biological characteristics and dynamic changes of the tumor. Therefore, there is a need for new biomarkers to improve CRC diagnosis and to monitor and treat CRC patients. Numerous studies have shown that "liquid biopsy" is a promising minimally invasive method for early CRC detection. A liquid biopsy mainly samples circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNA (miRNA) and extracellular vesicles (EVs). CTCs are malignant cells that are shed from the primary tumors and/or metastases into the peripheral circulation. CTCs carry information on both primary tumors and metastases that can reflect dynamic changes in tumors in a timely manner. As a promising biomarker, CTCs can be used for early disease detection, treatment response and disease progression evaluation, disease mechanism elucidation, and therapeutic target identification for drug development. This review will discuss currently available technologies for plasma CTC isolation and detection, their utility in the management of CRC patients and future research directions.

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