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1.
J Colloid Interface Sci ; 655: 809-821, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37979287

RESUMO

HYPOTHESIS: Tumor recurrence, bacterial infection, and wound healing remain significant clinical challenges after skin-tumor resection. In this study, we tested the hypothesis that a multifunctional nanocomposite platform containing nanoparticles (NPs) with the photothermal agent IR820 and bioactive drug curcumin (Cur) would be able to prevent tumor recurrence, limit bacterial wound infections, and promote wound healing. EXPERIMENTS: In this study, we developed a near-infrared light-activated nanocomposite hydrogel system (Hydrogel/Cur@IR820) by incorporating self-assembled NPs (Cur@IR820) in solutions containing Pluronic F127 modified with aldehyde groups (F127-CHO) and polyethyleneimine-grafted F127 (F127-PEI). FINDINGS: The Hydrogel/Cur@IR820 platform exhibited inherent multifunctional properties, including superior injectability, self-healing behavior, photothermal effects, and free radical scavenging ability. The Cur@IR820 NPs led to photonic hyperthermia and near-infrared (NIR)-triggered Cur release, which drove synergistic therapeutic effects against bacteria and tumor cells. Furthermore, the Hydrogel/Cur@IR820 system promoted wound repair and tissue regeneration by reducing inflammation through the antioxidant properties of Cur. Overall, the results of this study have clinical implications for inhibiting tumor growth, treating bacterial infections, and accelerating tissue regeneration.


Assuntos
Curcumina , Recidiva Local de Neoplasia , Humanos , Nanogéis , Recidiva Local de Neoplasia/patologia , Hidrogéis/farmacologia , Pele , Curcumina/farmacologia , Antibacterianos/farmacologia
2.
Food Chem ; 437(Pt 1): 137771, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37897825

RESUMO

Nanocarrier-delivered bioactive compounds are highly desirable for their improved stability and applicability, but their bioavailability is still limited due to the strong mucus and epithelial cell barriers. Herein, a series of self-assembled soy protein nanoparticles (SPNPs) with different mucus permeabilities were prepared and their delivery efficiency upon Curcumin (Cur) encapsulation was evaluated. Results demonstrated that the formed SPNPs-Cur exhibited high compatibility and cellular antioxidant accessibility. Besides, SPNPs enhanced the cellular uptake and transmembrane permeation of Cur, especially promoted the transportation of proto-Cur in addition to Cur metabolites. The SPNPs with the rapid mucus diffusion capacity presented more efficient transcytosis across the Caco-2 cell monolayer, which was mediated by a combination of paracellular and transcellular pathways. This work verified that mucus-permeable soy protein nanoparticles could be a promising delivery system for improving the bioavailability of bioactive compounds.


Assuntos
Curcumina , Nanopartículas , Humanos , Curcumina/farmacologia , Curcumina/metabolismo , Células CACO-2 , Proteínas de Soja/metabolismo , Transcitose , Muco/metabolismo , Portadores de Fármacos , Tamanho da Partícula
3.
Acta Neurol Taiwan ; 33(3): 90-102, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37848242

RESUMO

BACKGROUND: Paraquat is known to cause damage to various organs, including the brain. Although curcumin have anti-inflammatory and anti-oxidant properties, it is not yet clear how they relate to PQ-induced neurotoxicity. This study's objective was to compare the effects of curcumin and nanocurcumin on PQ-induced neurotoxicity in male rats. CONCLUSIONS: Treatment with curcumin and nano-curcumin improves brain function in PQ toxicity and nanocurcumin was more advantageous than ordinary curcumin.


Assuntos
Curcumina , Paraquat , Ratos , Masculino , Animais , Paraquat/toxicidade , Curcumina/farmacologia , Curcumina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Anti-Inflamatórios
4.
Carbohydr Polym ; 323: 121434, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37940300

RESUMO

Although various drug delivery systems that regulated Ca2+ concentration has been developed for tumor therapy, their application still presented significant challenges due to the complex preparation and introduction of a large number of inorganic molecules that might cause serious toxic effects. To solve these problems, a folate-functionalized carboxymethyl chitosan (CMCS)/calcium phosphate hybrid nanoparticle (CF/CaP) with Ca2+ production was designed to treat breast cancer combined with the Ca2+ inhibitory effect of encapsulated curcumin (Cur). It was demonstrated that the optimal CF/CaP nanoparticles loaded with Cur (C@CF/CaP) were spherical nanoparticles, which exhibited a smaller size at about 179 nm than non-targeted nanoparticles with size at about 234 nm. C@CF/CaP had good biocompatibility, high stability and acid responsive drug release. Compared with the neutral environment, the cumulative release of Cur was >70 % after culture for 36 h at pH 5.0. Compared with non-targeted nanoparticles, C@CF/CaP could specifically target tumor tissues and then enter tumor cells through folate receptor-mediated endocytosis. C@CF/CaP could cause mitochondrial Ca2+ overload, trigger the mitochondrial apoptotic pathway, destroy the mitochondrial structure and finally have good anti-tumor efficiency. The results proved that Ca2+ nanomodulators based on CMCS might provide a potential organelle targeting strategy for cancer therapy.


Assuntos
Neoplasias da Mama , Quitosana , Curcumina , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Cálcio , Quitosana/química , Ácido Fólico , Sistemas de Liberação de Medicamentos/métodos , Curcumina/farmacologia , Curcumina/uso terapêutico , Nanopartículas/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio
5.
Future Med Chem ; 15(22): 2051-2064, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37929594

RESUMO

Rheumatoid arthritis (RA) is an inflammatory disease. Curcumin can inhibit NF-κB and reduce the expression of inflammation-related genes. Aim: To evaluate the potential development of 6d in the clinical treatment of inflammatory diseases such as RA. Methods: Using a skeleton fusion strategy to synthesize curcumin analogues for 6d. This work evaluates anti-inflammatory activity by conducting anti-arthritis experiments (adjuvant-induced RA models) on rats. Western blot and ELISA were used to detect the expression of inflammatory-related proteins and cytokines. Molecular docking analysis confirmed the binding effect of 6d with active sites. Conclusion: 6d inhibits NF-κB has a protective effect on arthritis caused by RA.


Assuntos
Artrite Reumatoide , Curcumina , Piperidonas , Ratos , Animais , Curcumina/farmacologia , Curcumina/uso terapêutico , NF-kappa B , Piperidonas/farmacologia , Piperidonas/uso terapêutico , Simulação de Acoplamento Molecular , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Inflamação
6.
Inflammopharmacology ; 31(6): 3063-3079, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37934384

RESUMO

OBJECTIVE: Bronchoconstriction, along with inflammation and hyperresponsiveness is the characteristic feature associated with asthma, contributing to variable airflow obstruction, which manifests shortness of breath, cough and wheeze, etc. Histone deacetylases 8 (HDAC8) is the member of class I HDAC family and known to regulate microtubule integrity and muscle contraction. Therefore, we aimed to investigate the effects of HDAC8 inhibition in murine model of asthma using Pan-HDAC inhibitor curcumin (CUR) and HDAC8-specific inhibitor PCI-34051 (PCI), alone and in combination. MATERIALS AND METHODS: To develop asthmatic mouse model, Balb/c mice were sensitized and challenged with ovalbumin (OVA). CUR (10 mg/kg, pre, post, alone and combined treatment) and PCI (0.5 mg/kg), were administered through intranasal (i.n) route, an hour before OVA aerosol challenge. Effects of HDAC8 inhibition by CUR and PCI pretreatments were evaluated in terms of inflammation, oxidative stress and fibrosis markers. Efficacy of curcumin post-treatment (CUR(p)) was also evaluated simultaneously. RESULTS: Inflammatory cell recruitment, oxidative stress (reactive oxygen species, nitric oxide), histamine and Immunoglobulin E (IgE) levels and expression of fibrosis markers including hydroxyproline, matrix metalloproteinases-9 and alpha smooth muscle actin (MMP-9 and α-SMA) were significantly reduced by CUR, CUR(p), PCI-alone and combined treatments. Protein expressions of HDAC8, Nuclear factor-κB (NF-κB) accompanied by MAPKs (mitogen-activated protein kinases) were significantly reduced by the treatments. Structural alterations were examined by histopathological analysis and linked with the fibrotic changes. CONCLUSIONS: Present study indicates protective effects of HDAC8 inhibition in asthma using HDAC8 using CUR and PCI alone or in combination, attenuates airway inflammation, fibrosis and remodeling; hence, bronchoconstriction was accompanied through modulation of MAP kinase pathway.


Assuntos
Asma , Curcumina , Animais , Camundongos , Curcumina/farmacologia , Asma/tratamento farmacológico , Pulmão , Inflamação/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fibrose , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Modelos Animais de Doenças
7.
Proc Inst Mech Eng H ; 237(12): 1348-1365, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38031395

RESUMO

In this study, carboxylated carbon nanotube (CNT)-loaded curcumin (CUR) was blended into calcium phosphate cement (CPC) owing to the poor mechanical properties and single function of CPC as a bone-filling material, and CNT-CUR-CPC with improved strength and antitumor properties was obtained. The failure strength, hydrophilicity, in vitro bioactivity, bacteriostatic activity, antitumor activity, and cell safety of CNT-CUR-CPC were evaluated. The experimental results indicated that the failure strength of CNT-CUR-CPC increased from 25.05 to 45.05 MPa (p < 0.001) and its contact angle decreased from 20.37° to 15.27° (p < 0.001) after the CNT-CUR complex was added into CPC at the rate of 5 wt% and blended. Following soaking in simulated body fluid (m-SBF), the main components of CNT-CUR-CPC were hydroxyapatite (HA) and carbonate hydroxyapatite (HCA). The incorporation of CNT-CUR was beneficial for the deposition of PO43- and CO32-, and it promoted the crystallization of HA and HCA. For CNT-CUR-CPC, the inhibition zone diameter on Staphylococcus aureus was 10.2 ± 1.02 mm (p < 0.001) and it exhibited moderate sensitivity, whereas the inhibition zone diameter on Escherichia coli was 8.3 ± 0.23 mm (p < 0.001) and it exhibited low sensitivity. When compared with the CPC, the cell proliferation rate (RGR %) of the CNT-CUR-CPC decreased by 7.73% (p > 0.05) at 24 h, 17.89% (p < 0.05) at 48 h, and 24.43% (p < 0.001) at 72 h when MG63 cells were cultured on it. In particular, after the MG63 cells were cultured with the CNT-CUR-CPC for 48 h, the number of newly proliferating MG63 cells was significantly reduced, and their growth and adhesion on the surface of the CNT-CUR-CPC were inhibited when compared with the CPC. When 3T3-E1 cells were exposed to the m-SBF immersion solution of CNT-CUR-CPC, the cell proliferation rate (RGR %) was ≥80% (p > 0.05) and the cytotoxicity grade was 0-1. The 3T3-E1 cells were cultured with the m-SBF soaking solution of CNT-CUR-CPC for 24 h, and no significant changes in cell morphology or cytotoxicity were observed. After the 3T3-E1 cells were cultured on CNT-CUR-CPC for 48 h, they could stick to and grow on its surface without adverse reactions. CNT-CUR-CPC had a hemolysis rate of 4.3% (p > 0.05) and did not result in hemolysis and hemagglutination. The obtained CNT-CUR-CPC scaffold material exhibited effective antibacterial activity and cell safety, and could achieve a certain antitumor effect, which has a wide application potential in bone tissue engineering.


Assuntos
Curcumina , Nanotubos de Carbono , Humanos , Cimentos Ósseos/farmacologia , Cimentos Ósseos/química , Teste de Materiais , Curcumina/farmacologia , Hemólise , Força Compressiva , Fosfatos de Cálcio/química , Durapatita/farmacologia , Durapatita/química
8.
Cells ; 12(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37998354

RESUMO

AIM: The semisynthetic derivatives MePip-SF5 and isogarcinol, which are aligned with the natural products curcumin and garcinol, were tested for their antitumor effects in a preclinical model of pulmonary melanoma metastasis. METHODS AND RESULTS: MePip-SF5 was almost five times more effective in inhibiting B16F10 melanoma cell proliferation than its original substance of curcumin (IC50 MePip-SF5 2.8 vs. 13.8 µM). Similarly, the melanoma cytotoxicity of isogarcinol was increased by 40% compared to garcinol (IC50 3.1 vs. 2.1 µM). The in vivo toxicity of both drugs was assessed in healthy C57BL/6 mice challenged with escalating doses. Isogarcinol induced toxicity above a dose of 15 mg/kg, while MePip-SF5 showed no in vivo toxicity up to 60 mg/kg. Both drugs were tested in murine pulmonary metastatic melanoma. C57BL/6 mice (n = 10) received 500,000 B16F10 melanoma cells intravenously. After intraperitoneal injection of MePip-SF5 (60 mg/kg) or isorgarcinol (15 mg/kg) at days 8, 11 and 14 and sacrifice at day 16, the MePip-SF5-treated mice showed a significantly (p < 0.05) lower pulmonary macroscopic and microscopic tumor load than the vehicle-treated controls, whereas isogarcinol was ineffective. The pulmonary RNA levels of the mitosis marker Bub1 and the inflammatory markers TNFα and Ccl3 were significantly (p < 0.05) reduced in the MePip-SF5-treated mice. Both drugs were well tolerated, as shown by an organ inspection and normal liver- and kidney-related serum parameters. CONCLUSIONS: The novel curcuminoid MePip-SF5 showed a convincing antimetastatic effect and a lack of systemic toxicity in a relevant preclinical model of metastasized melanoma.


Assuntos
Curcumina , Neoplasias Pulmonares , Melanoma , Animais , Camundongos , Curcumina/farmacologia , Curcumina/uso terapêutico , Diarileptanoides/uso terapêutico , Camundongos Endogâmicos C57BL , Melanoma/tratamento farmacológico , Melanoma/patologia , Neoplasias Pulmonares/patologia
9.
J Cell Biochem ; 124(11): 1764-1778, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37909649

RESUMO

Curcumin, a kind of natural compound, has been previously proven to inhibit the autophagy in hepatic stellate cells (HSCs) and induce their apoptosis. However, it is not clear whether the enhanced apoptosis of activated HSCs (aHSCs) caused by curcumin depends on autophagy inhibition. We aim to verify this hypothesis and explore the potential mechanisms in this study. Immortalized human HSC line LX-2 was used as an experimental specimen and pretreated with transforming growth factor ß1(TGF-ß1) for 24 h to activate it before drug application. The levels of autophagy, apoptosis, cell activity, lipid metabolism, and the activity of the PI3K/Akt/mTOR signal pathway were evaluated by multiple methods, such as Western blotting, mcherry-EGFP-LC3B adenoviruses transfection, immunofluorescence, Nile Red staining, flow cytometry among others. Our results showed that rapamycin, an autophagy activator, could partly offset the effects of curcumin on autophagy and apoptosis of LX-2 cells, while 3-Methyladenine (3-MA), an autophagy inhibitor, could enhance these effects. Furthermore, curcumin could promote the activity of the PI3K/Akt/mTOR signal pathway in LX-2 cells, while PI3K inhibitor could partly offset this effect and increase the autophagy level. Overall, we demonstrated that curcumin could inhibit the activity and promote LX-2 cells apoptosis by suppressing autophagy by activating the PI3K/Akt/mTOR signal pathway. In addition, lipid recovery and energy deprivation due to autophagy inhibition may be the exact mechanism by which curcumin attenuates the pro-fibrotic activity of LX-2.


Assuntos
Curcumina , Células Estreladas do Fígado , Humanos , Células Estreladas do Fígado/metabolismo , Curcumina/farmacologia , Curcumina/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Cirrose Hepática/metabolismo
10.
J Mater Chem B ; 11(45): 10836-10844, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37929670

RESUMO

The efficiency of photodynamic therapy (PDT) is related to the subcellular localization of photosensitizers (PSs) because organelles are associated with many fundamental life-sustaining activities. In this work, we synthesized a PS (CN) based on curcumin (CUR) and obtained enhanced PDT efficiency by simultaneously targeting lipid droplets (LDs) and the endoplasmic reticulum (ER). Compared with CUR, CN with a D-π-A-π-D structure possessed stronger intramolecular charge transfer features, resulting in longer absorption and emission wavelengths. In cell imaging experiments of CN using a confocal laser scanning microscope, a bright green emission in LDs and a weak orange emission in the ER were simultaneously observed due to its sensitivity to polarity. Surprisingly, CN with low singlet oxygen yields (0.13) exhibited an excellent photodynamic effect. Further experimental results showed that the phototoxicity of CN resulted in apoptosis by destroying the ER and ferroptosis by oxidizing polyunsaturated fatty acids (PUFAs) in LDs. This work paves the way for developing more effective photosensitizers with superior dual-targeting specificity.


Assuntos
Curcumina , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Curcumina/farmacologia , Fotoquimioterapia/métodos , Retículo Endoplasmático , Oxigênio Singlete
11.
ACS Nano ; 17(22): 22355-22370, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37930078

RESUMO

Burns are among the most common causes of trauma worldwide. Reducing the healing time of deep burn wounds has always been a major challenge. Traditional dressings not only require a lengthy medical procedure but also cause unbearable pain and secondary damage to patients. In this study, we developed an exudate-absorbing and antimicrobial hydrogel with a curcumin-loaded magnesium polyphenol network (Cur-Mg@PP) to promote burn wound healing. That hydrogel was composed of an ε-poly-l-lysine (ε-PLL)/polymer poly(γ-glutamic acid) (γ-PGA) hydrogel (PP) and curcumin-loaded magnesium polyphenol network (Cur-Mg). Because of the strong water absorption property of ε-PLL and γ-PGA, Cur-Mg@PP powder can quickly absorb the wound exudate and transform into a moist and viscous hydrogel, thus releasing payloads such as magnesium ion (Mg2+) and curcumin (Cur). The released Mg2+ and Cur demonstrated good therapeutic efficacy on analgesic, antioxidant, anti-inflammation, angiogenesis, and tissue regeneration. Our findings provide a strategy for accelerating burn wound healing.


Assuntos
Anti-Infecciosos , Queimaduras , Curcumina , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , Hidrogéis/uso terapêutico , Magnésio , Cicatrização , Anti-Infecciosos/uso terapêutico , Queimaduras/tratamento farmacológico
12.
Turk J Med Sci ; 53(4): 883-893, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38031951

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide. Many factors such as stress, lifestyle, and dietary habits are known to play a role in the initiation and progression of the disease. Herbal therapeutic agents including curcumin can hold a great potential against cancer treatment; however, their efficacy on CRC is still under investigation. Herein, we evaluated the anticancer mechanism of curcumin on four different CRC cell lines. METHODS: Cells were treated with curcumin for 24, 48 and 72 h, and IC50 doses for each cell line were calculated. Mechanistic studies were conducted with the lowest IC50 dose determined for each cell line by evaluating apoptosis and necrosis, cell division, and NLRP3-mediated pyroptosis. RESULTS: Curcumin treatment significantly decreased viability while increasing the SubG1 phase in all cell lines tested, indicating apoptosis is the main programmed cell death pathway activated upon curcumin treatment in CRC. In terms of pyroptosis, components of NLRP3 inflammasome were found to be elevated in SW480 and HCT116 cell lines, although to a lesser extent in the latter, and NLRP3 inflammasome activation was not observed in LoVo and HT29 cells. DISCUSSION: Our results reveal that while curcumin effectively induces apoptosis, its effects on NLRP3-inflammasome mediated pyroptosis vary. Our results underline the need for further research focusing on the other inflammasome complexes to confirm the differential effects of curcumin on CRC.


Assuntos
Neoplasias Colorretais , Curcumina , Humanos , Inflamassomos/metabolismo , Inflamassomos/farmacologia , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Curcumina/farmacologia , Apoptose , Neoplasias Colorretais/tratamento farmacológico
13.
Molecules ; 28(22)2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-38005258

RESUMO

Photodynamic therapy (PDT) is an anticancer/antibacterial strategy in which photosensitizers (PSs), light, and molecular oxygen generate reactive oxygen species and induce cell death. PDT presents greater selectivity towards tumor cells than conventional chemotherapy; however, PSs have limitations that have prompted the search for new molecules featuring more favorable chemical-physical characteristics. Curcumin and its derivatives have been used in PDT. However, low water solubility, rapid metabolism, interference with other drugs, and low stability limit curcumin use. Chemical modifications have been proposed to improve curcumin activity, and metal-based PSs, especially ruthenium(II) complexes, have attracted considerable attention. This study aimed to characterize six Ru(II)-arene curcuminoids for anticancer and/or antibacterial PDT. The hydrophilicity, photodegradation rates, and singlet oxygen generation of the compounds were evaluated. The photodynamic effects on human colorectal cancer cell lines were also assessed, along with the ability of the compounds to induce ROS production, apoptotic, necrotic, and/or autophagic cell death. Overall, our encouraging results indicate that the Ru(II)-arene curcuminoid derivatives are worthy of further investigation and could represent an interesting option for cancer PDT. Additionally, the lack of significant in vivo toxicity on the larvae of Galleria mellonella is an important finding. Finally, the photoantimicrobial activity of HCurc I against Gram-positive bacteria is indeed promising.


Assuntos
Antineoplásicos , Complexos de Coordenação , Curcumina , Fotoquimioterapia , Rutênio , Humanos , Fármacos Fotossensibilizantes/química , Rutênio/farmacologia , Rutênio/química , Curcumina/farmacologia , Diarileptanoides , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Antineoplásicos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
14.
Sci Rep ; 13(1): 20770, 2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38008819

RESUMO

Tumor-associated inflammation plays a vital role in cancer progression. Among the various stromal cells, cancer-associated fibroblasts are promising targets for cancer therapy. Several reports have indicated potent anti-inflammatory effects attributed to Curcumin. This study aimed to investigate whether inhibiting the inflammatory function of cancer-associated fibroblasts (CAFs) with Curcumin can restore anticancer immune responses. CAFs were isolated from breast cancer tissues, treated with Curcumin, and co-cultured with patients' PBMCs to evaluate gene expression and cytokine production alterations. Blood and breast tumor tissue samples were obtained from 12 breast cancer patients with stage II/III invasive ductal carcinoma. Fibroblast Activation Protein (FAP) + CAFs were extracted from tumor tissue, treated with 10 µM Curcumin, and co-cultured with corresponding PBMCs. The expression of smooth muscle actin-alpha (α-SMA), Cyclooxygenase-2(COX-2), production of PGE2, and immune cell cytokines were evaluated using Real-Time PCR and ELISA, respectively. Analyzes showed that treatment with Curcumin decreased the expression of genes α-SMA and COX-2 and the production of PGE2 in CAFs. In PBMCs co-cultured with Curcumin-treated CAFs, the expression of FoxP3 decreased along with the production of TGF-ß, IL-10, and IL-4. An increase in IFN-γ production was observed that followed by increased T-bet expression. According to our results, Curcumin could reprogram the pro-tumor phenotype of CAFs and increase the anti-tumor phenotype in PBMCs. Thus, CAFs, as a component of the tumor microenvironment, are a suitable target for combination immunotherapies of breast cancer.


Assuntos
Neoplasias da Mama , Fibroblastos Associados a Câncer , Curcumina , Humanos , Feminino , Neoplasias da Mama/genética , Fibroblastos Associados a Câncer/metabolismo , Curcumina/farmacologia , Curcumina/uso terapêutico , Curcumina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Fibroblastos/metabolismo , Inflamação/patologia , Linhagem Celular Tumoral , Microambiente Tumoral
15.
Lasers Med Sci ; 38(1): 254, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932526

RESUMO

This study aimed to evaluate the effectiveness of antimicrobial photodynamic therapy (aPDT) utilizing nanotechnology-applied curcumin activated by blue LED (450 nm) on the elimination of microorganisms arranged in multispecies biofilms inside the root canals of extracted human teeth. Forty single-rooted human teeth were used; these were randomized into four experimental groups, each comprising 10 teeth: control group, no treatment; photosensitizer (PS) group, nanotechnology-applied curcumin alone; light group, blue LED used separately; and aPDT group, nanotechnology-applied curcumin activated by blue LED. To carry out the tests, the interiors of the root canals were inoculated with species of Candida albicans (ATCC 90029), Enterococcus faecalis (ATCC 29212), Escherichia coli (ATCC 25922), and methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), using a multispecies biofilm. After the incubation period, the canals were treated according to the experimental groups, with no treatment given in the control group. Studied inasmuch as the antimicrobial effectiveness of aPDT was concerned, it was observed that the greatest reduction in microbial counts using aPDTs was achieved against MRSA (mean reduction = 2.48 Log10 CFU/mL), followed by Escherichia coli (mean reduction = 1.72), and Enterococcus faecalis (mean reduction = 1.65); a reduction greater than 1.5 Log10 CFU/mL showed relevant effectiveness of aPDT against these microorganisms. Of note, aPDT has also shown considerable effectiveness against Candida albicans (mean reduction = 0.71), with a statistical difference in the reduction between the groups. aPDT was effective in reducing all microorganisms examined. The average reduction was greater than 1.5 Log10 in all microorganisms except for Candida albicans. HIGHLIGHTS: • aPDT was a viable treatment for root canals; • Nanotechnological curcumin aPDT was effective in reducing multispecies biofilm microorganisms; • aPDT technique showed efficacy under the worst microbiological conditions , such as mature multispecies biofilm; • Nanotechnological curcumin aPDT was able to reduce Gram positive, negative bacterial and yeasts in root canals.


Assuntos
Anti-Infecciosos , Curcumina , Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Humanos , Curcumina/farmacologia , Cavidade Pulpar , Fotoquimioterapia/métodos , Anti-Infecciosos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Candida albicans , Biofilmes , Escherichia coli
16.
Sci Rep ; 13(1): 19389, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938669

RESUMO

In recent years, several nanocarrier synthesis methods have been developed. In cancer therapy, the use of smart nanocarriers is of interest. Smart nanocarriers respond to their environment and can release their cargo in a controlled manner under the action of internal or external stimuli. In this work, we report on the development of an aerosol-assisted method for the synthesis of curcumin-loaded chitosan/alginate-based polymeric nanocarrier (CurNCs). A custom-fabricated multi-nebulizer system was utilized for the synthesis of CurNCs. The developed system comprises three main parts a sprayer, an electric heater tunnel, and a collector. Curcumin and chitosan solutions were sprayed using a pneumatic multinebulizer into the electric heater tunnel to form chitosan-curcumin assemblies. Then, the aerosol was guided into the collector solution containing sodium alginate and tri-poly phosphate aqueous solution for further cross-linkage. The synthesized CurNCs were characterized using TEM, DLS, and FTIR techniques. The TEM size of the nanoparticles was 8.62 ± 2.25 nm. The release experiments revealed that the nanocarrier is sensitive to the environment pH as more curcumin is released at acidic pH values (as is the case for cancerous tissues) compared to physiological pH. The curcumin content of the nanocarrier was 77.27 mg g-1 with a drug loading efficiency of 62%. The in-vitro cytotoxicity of the synthesized nanocarrier was evaluated against the MCF7 breast cancer cell line. The IC50 concentrations for CurNCs and curcumin were obtained as 14.86 and 16.45 mg mL-1, respectively. The results showed that while the empty nanocarrier shows non-significant cytotoxicity, the CurNCs impact the cell culture and cause prolonged cell deaths. Overall, pH-responsive curcumin polymeric nanocarrier was synthesized using a custom fabricated aerosol-based method. The method enabled fast and feasible synthesis of the nanocarrier with high efficiency.


Assuntos
Antineoplásicos , Quitosana , Curcumina , Curcumina/farmacologia , Aerossóis , Alginatos , Polímeros , Antineoplásicos/farmacologia , Concentração de Íons de Hidrogênio
17.
AAPS PharmSciTech ; 24(8): 222, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37935931

RESUMO

This study reports on the synthesis of Mn1 - xZnxFe2O4 (Mn, Zn ferrite) magnetic nanoparticles (MNPs) as drug delivery carriers for effective therapeutic outcomes. The MNPs were prepared using the coprecipitation method, and their magnetic properties were investigated based on their composition. Among the compositions tested, Mn0.8Zn0.2Fe2O4 MNPs exhibited superparamagnetic properties with a saturation magnetization moment of 34.6 emu/g at room temperature (25°C). To enhance the water solubility of curcumin (Cur), known for its hydrophobic nature, it was successfully loaded onto alginate (Alg)/chitosan (Chit)@Mn0.8Zn0.2Fe2O4 nanoparticles (NPs). The nanocomposite was characterized by field emission scanning electron microscopy (FE-SEM) which revealed a particle size of approximately 20 nm. The crystalline structure of the NPs was analyzed using X-ray diffraction, while Fourier-transform infrared (FTIR), energy-dispersive X-ray, and map analysis techniques were employed for further characterization. In terms of drug release, there was an initial burst release of Cur (around 18%) within the first hour, followed by a slower release (approximately 61%) over the next 36 h. The anti-tumor properties of the Cur-loaded NPs were evaluated using the Methyl Thiazol Tetrazolium (MTT) assay and quantitative real-time polymerase chain reaction. The MTT assay confirmed a higher cytotoxic effect of Cur-loaded Alg/Chit@Mn0.8Zn0.2Fe2O4 NPs on the MCF-7 breast cancer cell line compared to free Cur, highlighting the significance of incorporating Cur into nano-sized carrier systems.


Assuntos
Neoplasias da Mama , Quitosana , Curcumina , Nanopartículas , Humanos , Feminino , Curcumina/farmacologia , Curcumina/química , Quitosana/química , Alginatos/química , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Nanopartículas/química , Zinco , Tamanho da Partícula
18.
Lasers Med Sci ; 38(1): 260, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37946038

RESUMO

This study aimed to investigate the photodynamic effects of curcumin, nanomicelle curcumin, and erythrosine on Lactobacillus casei (L. casei). Various concentrations of curcumin (1.5 g/L, 3 g/L), nano-curcumin (3 g/L), and erythrosine (100 µM/L, 250 µM/L) were tested either alone or combined with light irradiation (PDT effect) against L. casei in planktonic and biofilm cultures. The light was emitted from a light-emitting diode (LED) with a central wavelength of 450 nm. A 0.12% chlorhexidine digluconate (CHX) solution served as the positive control, and a solution containing neither photosensitizer nor light was the negative control group. The number of viable microorganisms was determined using serial dilution. There was a significant difference in the viability of L. casei in both planktonic and biofilm forms (P < 0.05). In the planktonic culture, the antibacterial effects of CHX and PDT groups with curcumin 3 g/L and erythrosine 250 µM/L were significantly greater than the other groups (P < 0.05). For L. casei biofilms, the greatest toxic effects were observed in CHX and PDT groups with curcumin 3 g/L, erythrosine 250 µmol/L, erythrosine 100 µmol/L, and nanomicelle curcumin 3 g/L, with a significant difference to other groups (P < 0.05). The antibacterial effects of all photosensitizers (except erythrosine 250 µmol/L at planktonic culture) enhanced significantly when combined with light irradiation (P < 0.05). PDT with curcumin 3 g/L or erythrosine 250 µmol/L produced comparable results to CHX against L. casei at both planktonic and biofilm cultures. Alternatively, PDT with erythrosine 100 µmol/L or nanomicelle curcumin 3 g/L could be suggested to kill L. casei biofilms.


Assuntos
Anti-Infecciosos , Curcumina , Lacticaseibacillus casei , Fotoquimioterapia , Eritrosina/farmacologia , Fotoquimioterapia/métodos , Curcumina/farmacologia , Streptococcus mutans/efeitos da radiação , Fármacos Fotossensibilizantes/farmacologia , Anti-Infecciosos/farmacologia , Biofilmes , Antibacterianos/farmacologia
19.
ACS Appl Bio Mater ; 6(11): 5086-5096, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37943145

RESUMO

The autoluminescence nanoplatform based on a single-atom catalyst has the potential to achieve accurate tumor diagnosis and treatment. Taking advantage of this, glycyrrhetinic acid (GA) and chitosan-modified single Fe-N-C atom catalysts (SAF NPs) loaded with luminol-curcumin (Cur) were fabricated (SAF-LCCG). Once delivered to the tumor, this autoluminescence SAF-LCCG could target the mitochondria to restrain tumor metastasis and promote the production of hydrogen peroxide (H2O2). Then, SAF NPs with Fenton-like properties could actively utilize intracellular H2O2 to produce ·OH for chemodynamic therapy. After that, excess ·OH and H2O2 were transmitted to luminol to emit blue-violet chemiluminescence (CL) for cancer cell imaging. Synchronously, light was transferred to Cur to produce reactive oxygen species (ROS) which realized photodynamic therapy. Besides, Cur could be served as a chemotherapeutic drug to enhance intracellular ROS for penetrating therapy. More importantly, the massive accumulation of ROS in cancer cells can promote the CL intensity of luminol, which realized the cyclic ROS amplification. This autoluminescence nanoplatform was developed for accurate cancer cell imaging, effective inhibition of tumor metastasis, and synergistic and penetrated treatment of tumors.


Assuntos
Curcumina , Neoplasias , Humanos , Peróxido de Hidrogênio , Luminol , Espécies Reativas de Oxigênio , Curcumina/farmacologia , Curcumina/uso terapêutico , Mitocôndrias , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
20.
Int J Mol Sci ; 24(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37958582

RESUMO

In both healthcare and agriculture, antibiotic resistance is an alarming issue. Biocompatible and biodegradable ingredients (e.g., curcumin) are given priority in "green" criteria supported by the Next Generation EU platform. The solubility and stability of curcumin would be significantly improved if it were enclosed in nanobubbles (NB), and photoactivation with the correct wavelength of light can increase its antibacterial efficacy. A continuous release of curcumin over a prolonged period was provided by using innovative chitosan-shelled carriers, i.e., curcumin-containing nanobubbles (Curc-CS-NBs) and oxygen-loaded curcumin-containing nanobubbles (Curc-Oxy-CS-NBs). The results demonstrated that after photoactivation, both types of NBs exhibited increased effectiveness. For Staphylococcus aureus, the minimum inhibitory concentration (MIC) for Curc-CS-NBs remained at 46 µg/mL following photodynamic activation, whereas it drastically dropped to 12 µg/mL for Curc-Oxy-CS-NBs. Enterococcus faecalis shows a decreased MIC for Curc-CS-NB and Curc-Oxy-CS-NB (23 and 46 µg/mL, respectively). All bacterial strains were more effectively killed by NBs that had both oxygen and LED irradiation. A combination of Curc-Oxy-CS-NB and photodynamic stimulation led to a killing of microorganisms due to ROS-induced bacterial membrane leakage. This approach was particularly effective against Escherichia coli. In conclusion, this work shows that Curc-CS-NBs and Curc-Oxy-CS-exhibit extremely powerful antibacterial properties and represent a potential strategy to prevent antibiotic resistance and encourage the use of eco-friendly substitutes in agriculture and healthcare.


Assuntos
Anti-Infecciosos , Quitosana , Curcumina , Curcumina/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Quitosana/farmacologia , Solubilidade
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