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High entropy material (HEM) has emerged as an appealing material platform for various applications, and specifically, the electrochemical performances of HEM could be further improved through self-assembled structure design. However, it remains a big challenge to construct such high-entropy self-assemblies primarily due to the compositional complexity. Herein, we propose a bottom-up directional freezing route to self-assemble high-entropy hydrosols into porous nanosheets. Taking Prussian blue analogue (PBA) as an example, the simultaneous coordination-substitution reactions yield stable high-entropy PBA hydrosols. During subsequent directional freezing process, the anisotropic growth of ice crystals could guide the two-dimensional confined assembly of colloidal nanoparticles, resulting in high-entropy PBA nanosheets (HE-PBA NSs). Thanks to the high-entropy and self-assembled structure design, the HE-PBA NSs manifests markedly enhanced sodium storage kinetics and performances in comparison with medium/low entropy nanosheets and high entropy nanoparticles.
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Reactive carbonyl species (RCS), including acrolein (ACR), methylglyoxal (MGO), and glyoxal (GO), are typically generated in food processing and accumulate in the body for ages, triggering various chronic diseases. Here, we investigated the capture capability and reaction pathways of mangiferin one-to-one and one-to-many on RCS in high temperatures using UPLC-MS/MS. We found that mangiferin can capture ACR/MGO/GO to form their adducts, yet, the ability to capture RCS is arranged in different orders, with ACR > MGO > GO for a single RCS and MGO > ACR > GO for multiple RCS. After synthesizing and identifying the structures of the ACR- and MGO-adducts of MGF, our results indicated that MGF-ACR-MGO produced in the multiple-RCS-MGF system was formed by capturing MGO through MGF-ACR rather than through MGF-MGO capturing ACR, which resulting in higher inhibitory activity of MGF against MGO than against ACR. Then, the capture ability and path of MGF on RCS were verified in the coffee-leaves tea and cake.
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Prodigiosin (PG) is a red tripyrrole pigment from the prodiginine family that has attracted widespread attention due to its excellent biological activities, including anticancer, antibacterial and anti-algal activities. The synthesis and production of PG is of particular significance, as it has the potential to be utilized in a number of applications, including those pertaining to clinical drug development, food safety, and environmental management. This paper provides a systematic review of recent research on PG, covering aspects like chemical structure, bioactivity, biosynthesis, gene composition and regulation, and optimization of production conditions, with a particular focus on the biosynthesis and regulation of PG in Serratia marcescens. This provides a solid theoretical basis for the drug development and production of PG, and is expected to promote the further development of PG in medicine and other applications.
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There is considerable research evidence that α-dicarbonyl compounds, including glyoxal (GO) and methylglyoxal (MGO), are closely related to many chronic diseases. In this work, after comparison of the capture capacity, reaction pathway, and reaction rate of synephrine (SYN) and neohesperidin (NEO) on GO/MGO in vitro, experimental mice were administrated with SYN and NEO alone and in combination. Quantitative data from UHPLC-QQQ-MS/MS revealed that SYN/NEO/HES (hesperetin, the metabolite of NEO) could form the GO/MGO-adducts in mice (except SYN-MGO), and the levels of GO/MGO-adducts in mouse urine and fecal samples were dose-dependent. Moreover, SYN and NEO had a synergistic scavenging effect on GO in vivo by promoting each other to form more GO adducts, while SYN could promote NEO to form more MGO-adducts, although it could not form MGO-adducts. Additionally, human experiments showed that the GO/MGO-adducts of SYN/NEO/HES found in mice were also detected in human urine and fecal samples after drinking flowers of Citrus aurantium L. var. amara Engl. (FCAVA) tea using UHPLC-QTOF-MS/MS. These findings provide a novel strategy to reduce endogenous GO/MGO via the consumption of dietary FCAVA rich in SYN and NEO.
Assuntos
Citrus , Hesperidina/análogos & derivados , Aldeído Pirúvico , Humanos , Animais , Camundongos , Glioxal , Sinefrina , Espectrometria de Massas em Tandem , Óxido de Magnésio , FloresRESUMO
α-Dicarbonyl compounds, such as glyoxal (GO) and methylglyoxal (MGO), are a series of chemical hazards that exist in vivo and in vitro, posing a threat to human health. We aimed to explore the scavenging effects on GO/MGO by synephrine (SYN) alone or in combination with neohesperidin (NEO). First, through LC-MS/MS, we confirmed that both SYN and NEO could effectively remove GO and form GO adducts, while NEO could also clear MGO by forming MGO adducts, and its ability to clear MGO was stronger than that of GO. Second, a synergistic inhibitory effect on GO was found when SYN and NEO were used in combination by using the Chou-Talalay method; on the other hand, SYN could promote NEO to clear more MGO, although SYN could not capture MGO. Third, after synthesizing four GO/MGO-adducts (SYN-GO-1, SYN-GO-3, NEO-GO-7, and NEO-MGO-2) and identifying their structure through NMR, strict correlations between the GO/MGO-adducts and the GO/MGO-clearance rate were found when using SYN and NEO alone or in combination. Furthermore, it was inferred that the synergistic effect between SYN and NEO stems from their mutual promotion in capturing more GO by the quantitative analysis of the adducts in the combined model. Finally, a study was conducted on flowers of Citrus aurantium L. var. amara Engl. (FCAVA, an edible tea) rich in SYN and NEO, which could serve as an effective GO and MGO scavenger in the presence of both GO and MGO. Therefore, our study provided well-defined evidence that SYN and NEO, alone or in combination, could efficiently scavenge GO/MGO at high temperatures, whether in the pure form or located in FCAVA.
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Glioxal , Hesperidina/análogos & derivados , Aldeído Pirúvico , Humanos , Aldeído Pirúvico/química , Glioxal/química , Sinefrina , Cromatografia Líquida , Óxido de Magnésio , Temperatura , Espectrometria de Massas em TandemRESUMO
One of the crucial issues for applying electret/triboelectric power generators in the Internet of Things (IoT) is to take full advantage of specific high voltage signals and enable self-powered sensing. Therefore, inspired by Miura-origami, we present an innovative origami power generator (OPG) constructed from only one piece of electret thin film. The Miura-origami architecture realizes a generator with excellent deformability and stretchability and makes it unnecessary for any auxiliary support structure during the compress-release cycle. Various parameters of the generator are intensively investigated, including the excitation accelerations, excitation displacements, numbers of power generation units and deformation degree of the device. When stimulated with 5.0 g acceleration at 15 Hz frequency, the generator with 8 generation units can obtain an instantaneous peak-to-peak voltage and a remarkable optimum peak power of 328 V and 2152 µW at 50 MΩ, respectively. In addition, the regulable shape and multiple generation modes of the device greatly improve its applicability in various vibration energy collection requirements. Based on the above results, a hexagonal electret generator integrated with six-phase OPGs is developed as a "Buoy on Sky," after which the signal waveforms generated from internal power generators are recognized with 92% accuracy through a neural network algorithm that identifies the vibration conditions of transmission lines. This work demonstrates that a fusion of origami art and energy conversion techniques can achieve a multifunctional generator design satisfying the requirements for IoT applications.
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It is unclear whether membrane vitamin D receptor (mVDR) exists on the macrophage membrane or whether mVDR is associated with lipopolysaccharide (LPS) tolerance. Herein, we report that interfering with caveolae and caveolae-dependent lipid rafts inhibited the formation of LPS tolerance. VDR was detected as co-localized with membrane molecular markers. VDR was detected on the cell membrane and its level was higher in LPS-tolerant cells than that in only LPS treatment cells. Anti-VDR antibodies could abolish the effect of artesunate (AS) to reverse LPS tolerance, and the wild-type peptides (H397 and H305) of VDR, but not the mutant peptide (H397D and H305A), led to the loss of AS's effect. AS decreased the mVDR level in LPS-tolerant cells. In vivo, AS significantly reduced VDR level in the lung tissue of LPS-tolerant mice. In summary, mVDR exists on the cell membrane of macrophages and is closely associated with the formation of LPS tolerance and the effects of AS. Video Abstract.
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Lipopolissacarídeos , Receptores de Calcitriol , Camundongos , Animais , Receptores de Calcitriol/metabolismo , Lipopolissacarídeos/farmacologia , Artesunato/farmacologia , Membrana Celular/metabolismo , Macrófagos/metabolismoRESUMO
Herein, a multi-functional nanoplatform (PDA-DTC/Cu-MnO2) was established, which has been employed for MR imaging-guided multi-therapy (CDT, PTT and chemotherapy) for cancer treatment. The in vitro and in vivo results confirmed that the biocompatible nanoplatform could significantly induce tumor cell death and inhibit tumor growth.
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Antineoplásicos/farmacologia , Imageamento por Ressonância Magnética , Nanopartículas/química , Neoplasias de Mama Triplo Negativas/diagnóstico por imagem , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Ditiocarb/química , Ditiocarb/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Indóis/química , Indóis/farmacologia , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/tratamento farmacológico , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Camundongos , Estrutura Molecular , Imagem Óptica , Óxidos/química , Óxidos/farmacologia , Tamanho da Partícula , Polímeros/química , Polímeros/farmacologiaRESUMO
[This corrects the article DOI: 10.3389/fchem.2019.00853.].
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A combination of chemotherapy and phototherapy has been proposed as a promising treatment for esophageal cancer (EC). Irinotecan as a first-line treatment option is widely prescribed for metastatic EC, however, its clinical application is extremely restricted by the low conversion rate to SN38, severe myelosuppression and diarrhea. As a more potent active metabolite of irinotecan, SN38 is a better substitution for irinotecan, but the poor water solubility and the difficulty of encapsulation hindered its medical application. Herein, a multifunctional SN38-conjugated nanosystem (FA-PDA@PZM/SN38@BSA-MnO2, denoted as FA-PPSM) is designed for overcoming the above-mentioned drawbacks and achieving collaborative chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT). The tumor acidic microenvironment induces decomposition of BSA-MnO2 nanoparticles into O2 and Mn2+, thus enhancing oxygen-dependent PDT efficacy; meanwhile, Mn2+ can be employed as a magnetic resonance imaging (MRI) contrast agent. Under 650 and 808 nm laser irradiation, the FA-PPSM nanocomposites exhibit superior antitumor efficacy in Eca-109-tumor bearing mice. Notably, there is low gastrointestinal toxicity and myelosuppression in the FA-PPSM treated mice compared with those treated with irinotecan (alone). Taken together, this work highlights the great potential of the FA-PPSM nanocomposites for MRI-guided chemotherapy in combination with endoscopic light therapy for esophageal cancer.
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Neoplasias Esofágicas , Nanopartículas , Animais , Linhagem Celular Tumoral , Diarreia , Neoplasias Esofágicas/tratamento farmacológico , Irinotecano , Compostos de Manganês , Camundongos , Óxidos , Fototerapia , Microambiente TumoralRESUMO
Inhibition of Tau protein aggregation is an attractive therapeutic target for Alzheimer's disease. However, most of the inhibitors have failed in clinical trials due to the superficial understanding of inhibition mechanism and drug-transfer pharmacokinetics. Innovation of design strategy has become a top priority. To afford a hairpinlike molecular inhibitor, we introduced tannic acid, a multibranched polyphenol molecule, and its moiety, gallic acid. We showed that tannic acid could effectively inhibit Tau aggregation through a multidentate chelation mode. We then encapsulated tannic acid in a non-neurotoxic liposome by lecithin/ß-sitosterol, overcoating with Tween 80. Using transwell devices, we cytologically demonstrated that tannic acid liposome can successfully be transferred across the model of a blood-brain barrier made up of mouse brain microvascular endothelial cell bEnd.3 and effectively reduce Tau aggregation induced by fibrils of Tau peptide R3 in human neuroblastoma cell SK-N-SH. This result indicates the potential therapeutic effect of tannic acid liposome on Alzheimer's disease.
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Doença de Alzheimer , Lipossomos , Doença de Alzheimer/tratamento farmacológico , Barreira Hematoencefálica/metabolismo , Humanos , Peptídeos , Taninos , Proteínas tau/metabolismoRESUMO
Maximizing the accumulation of anticancer medicine in the tumor is the priority to achieve minimal invasive cancer therapy, which raises high demands on tumor-targeting ability of drug delivery systems. Herein, we adopted an emerging "cell-drug" strategy via the nanoplatform construction to achieve high aggregation and intratumoral distribution. We fabricated gold nanostars (GNSs) with HER-2 monoclonal antibody (trastuzumab) and near-infrared region (NIR) photosensitizer indocyanine green (ICG) to obtain GNS@ICG-Ab, which combined the photothermal therapy with photodynamic therapy (PTT/PDT) that rely on enhanced photothermal conversion efficiency of GNS and 1O2 generator ICG under the exposure of a NIR laser. Tumor-tropism CIK cells loaded with GNS@ICG-Ab were able to migrate into tumors and make a difference in efficient accumulation and uniform distribution of the GNS@ICG-Ab-CIK nanoplatform inside tumors based on fluorescence, photoacoustic (PA), and computed tomography (CT) imaging observations. Encouraged by the improvements in tumor targeting and retention presented by real-time imaging, we employed the novel nanoplatform to synergistically inhibit the progression of tumors in SK-BR-3 tumor-bearing mice via PTT/PDT and immunotherapy-implemented by CIK cells for activating the immune response, and with the specific linkage between trastuzumab and SK-BR-3 tumor cells, our platform could exert a precise strike of PDT/PTT. Taken together, the integrating tri-modal imaging with tri-modal therapy endows CIK-GNS@ICG-Ab with promising potential in cancer theranostics and lays a solid foundation for the development of immune cell application in nanomedicine delivery.
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Células Matadoras Induzidas por Citocinas/imunologia , Nanopartículas Metálicas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Trastuzumab/uso terapêutico , Animais , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/uso terapêutico , Linhagem Celular Tumoral , Ouro/química , Humanos , Verde de Indocianina/química , Verde de Indocianina/efeitos da radiação , Verde de Indocianina/uso terapêutico , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Receptor ErbB-2/imunologia , Nanomedicina Teranóstica , Trastuzumab/química , Trastuzumab/imunologiaRESUMO
Despite its great potential in cancer therapy, phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), often cause metastasis of tumors. Immunotherapy has revolutionized the cancer treatment owing to the capability of activating immune system to eliminate tumors. However, the integration of phototherapy and immunotherapy in a single nanoagent for cancer therapy is still a challenging task. Here, we fabricated (Cu9S5@mSiO2-PpIX@MnO2@CpG (CSPM@CpG)) as a synergistic therapeutic model for phototherapy enhanced immunotherapy. The intracellular uptake of cytosine-phosphate-guanine (CpG) promoted the infiltration of cytotoxic T lymphocytes (CTLs) in tumor tissue, further stimulating the production of interferon gamma (IFN-γ) and remarkably elevating the immune response level. Excellent anti-tumor effects have been achieved by synergistic PTT/PDT/immunotherapy. The metastasis of tumors was effectively inhibited by the immune response of CpG. Thus, our proposed work provides a strategy to combine phototherapy with immunotherapy to enhance the therapeutic efficiency and further inhibit metastasis of tumors.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Cobre/química , Sistemas de Liberação de Medicamentos , Temperatura Alta , Nanopartículas Metálicas/administração & dosagem , Fotoquimioterapia/métodos , Animais , Antineoplásicos/química , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Citosina/química , Liberação Controlada de Fármacos , Feminino , Guanina/química , Humanos , Imunoterapia , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Óxidos/química , Fosfatos/química , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Multifunctional nanotheranostic systems with both therapeutic and imaging functions are highly desired for the development of more effective and less toxic anti-tumor drugs. Herein, a simple but effective method is reported to fabricate a novel PCN-CuS-FA-ICG-based nanoplatform for dual-modal imaging-guided synergistic photothermal/photodynamic therapy. Porphyrinic metal-organic frameworks with CuS NPs are obtained in aqueous solution via a simple post-synthesis strategy. Furthermore, to obtain a more effective therapy, indocyanine green (ICG) was incorporated into the multifunctional theranostic platform to promote the photothermal therapeutic effect. The as-prepared PCN-CuS-FA-ICG not only exhibits an excellent 1O2 generation efficiency under 650 nm irradiation to achieve remarkable photodynamic cell killing, but also presents outstanding photothermal conversion under 808 nm irradiation to destroy tumor tissues by hyperthermia. In particular, the nanotherapeutic agent realized fluorescence and thermal imaging dual-modal imaging-guided cancer treatment. Meanwhile, in vivo experiments confirmed the evident accumulation of nanoparticles (NPs) at local tumors, and tumor growth was inhibited obviously via synergistic photothermal/photodynamic therapy with negligible side effects.
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Antineoplásicos/farmacologia , Corantes/farmacologia , Hipertermia Induzida , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Fotoquimioterapia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cobre/química , Cobre/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Raios Infravermelhos , Teste de Materiais , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Imagem Óptica , Tamanho da Partícula , Oxigênio Singlete/análise , Oxigênio Singlete/metabolismo , Propriedades de Superfície , Células Tumorais CultivadasRESUMO
Despite drug delivery nanoplatforms receiving extensive attention, development of a simple, effective, and multifunctional theranostics nanoplatform still remains a challenge. Herein, a versatile nanoplatform based on a zirconium framework (UiO-66-N3 ) was synthesized, which demonstrated a combined photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy (CT) for cancer treatment. A RuII polypyridyl alkyne complex (Ra) as a photosensitizer was modified into a nanoplatform by click reactions for the first time. When exposed to suitable light irradiation, the as-prepared multifunctional nanoplatform (UiO-Ra-DOX-CuS) not only demonstrated efficient 1 O2 generation, but also exhibited excellent photothermal conversion ability. In particular, the nanotherapeutic agent presented a dual-stimuli response; either acidic environment or NIR laser irradiation would trigger the drug release. The synergetic efficacy of UiO-Ra-DOX-CuS combined PDT, PTT, and CT, which was evaluated by cell experiments. Moreover, the design could promote the development of RuII polypyridyl alkyne complexes based multifunctional nanoparticles and multimodal cancer treatment.
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Alcinos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Compostos de Rutênio/química , Terapia Combinada , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Quimioterapia Combinada , Humanos , Estruturas Metalorgânicas , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Nanomedicina TeranósticaRESUMO
Photodynamic therapy (PDT) has shown great promise in breast cancer treatment. However, simplex target ligand modification or stimuli release cannot meet the requirement of effective drug delivery to solid tumor tissue. To overcome continuous bio-barriers existing in the tumor microenvironment, multi-stage response drug delivery was desirable. Herein, we developed a unique tumor microenvironment tailored nanoplatform for chlorin e6 (Ce6) delivery. We chose bovine serum albumin (BSA) as "mother ships" material for effective tumor periphery resident, cyclopamine (CYC) as extracellular matrix (ECM) inhibitor and synergistic anti-tumor agent, and diselenide containing amphiphilic hyaluronic acid-chlorin e6 polymers (HA-SeSe-Ce6) synthesized as "small bombs" for internal tissue destruction. The above three distinct function compositions were integrated into an independent CYC and HA-SeSe-Ce6 co-delivery albumin nano-system (ABN@HA-SeSe-Ce6/CYC). The obtained nano-system presents good biocompatible, long circulation and effective tumor accumulation. After entering tumor microenvironment, CYC gradually releases to disrupt the ECM barrier to open the way for further penetration of HA-SeSe-Ce6. Subsequently, targeted tumor cell internalization and intracellular redox response release of Ce6 would achieve. Moreover, CYC could also make up the deficiency of Ce6 in hypoxia area, owing to its anti-tumor effect. Improved therapeutic efficacy was verified in a breast cancer cell line and tumor-bearing mice model.
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Based on the Pt nanozyme modified mesoporous polydopamine in situ, a multi-functional nanoplatform was established, which could overcome tumour hypoxia by catalyzing overexpressed H2O2 in tumour cells to enhance photodynamic therapy. In vivo results confirmed that the tumour growth was inhibited efficiently by synergetic therapy.
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Antineoplásicos/química , Indóis/química , Nanopartículas Metálicas/química , Polímeros/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Clorofilídeos , Doxorrubicina/química , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Peróxido de Hidrogênio/metabolismo , Lasers , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Platina/química , Porosidade , Porfirinas/química , Soroalbumina Bovina/químicaRESUMO
Cancer immunotherapy has achieved promising clinical responses in recent years owing to the potential of controlling metastatic disease. However, there is a limited research to prove the superior therapeutic efficacy of immunotherapy on breast cancer compared with melanoma and non-small-cell lung cancer because of its limited expression of PD-L1, low infiltration of cytotoxic T lymphocytes (CTLs), and high level of myeloid-derived suppressor cells (MDSCs). Herein, a multifunctional nanoplatform (FA-CuS/DTX@PEI-PpIX-CpG nanocomposites, denoted as FA-CD@PP-CpG) for synergistic phototherapy (photodynamic therapy (PDT), photothermal therapy (PTT) included) and docetaxel (DTX)-enhanced immunotherapy is successfully developed. The nanocomposites exhibit excellent PDT efficacy and photothermal conversion capability under 650 and 808 nm irradiation, respectively. More significantly, FA-CD@PP-CpG with no obvious side effects can remarkably inhibit the tumor growth in vivo based on a 4T1-tumor-bearing mice modal. A low dosage of loaded DTX in FA-CD@PP-CpG can promote infiltration of CTLs to improve efficacy of anti-PD-L1 antibody (aPD-L1), suppress MDSCs, and effectively polarize MDSCs toward M1 phenotype to reduce tumor burden, further to enhance the antitumor efficacy. Taken together, FA-CD@PP-CpG nanocomposites offer an efficient synergistic therapeutic modality in docetaxel-enhanced immunotherapy for clinical application of breast cancer.
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Docetaxel/química , Oligonucleotídeos/química , Linfócitos T Citotóxicos/imunologia , Animais , Anticorpos Monoclonais Humanizados/química , Anticorpos Monoclonais Humanizados/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Portadores de Fármacos/química , Ácido Fólico/química , Humanos , Imunoterapia , Lasers , Camundongos , Nanocompostos/química , Fototerapia , Polietilenoimina/química , Protoporfirinas/química , Espécies Reativas de Oxigênio/metabolismo , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Combination chemotherapy is considered to be one of the most effective treatments for breast cancer by reducing the emergence of drug resistance. In this study, a novel drug delivery system based on bovine serum albumin nanoparticles (BSA NPs) was successfully developed. Doxorubicin (DOX) and cyclopamine (CYC), a potential anti-cancer agent that inhibits the hedgehog signaling pathway were entrapped into BSA NPs through electrostatic interactions and hydrophobic interactions, respectively. Rather than simple combination of two different chemotherapeutics, the CYC also increased the intracellular DOX accumulation by decreasing the expression of P-glycoprotein (P-gp), which could thus reverse the DOX resistance. Tumor-targeting property of nanoparticles was the prerequisite for its further application. Interestingly, retention of fluorescently-labeled particles in vivo indicated that the dual-drug-loaded BSA NPs could not only target the primary tumors, but also target the metastatic lymph nodes, which would simultaneously inhibit the tumor growth and distant metastasis. Taken together, this study provides a promising strategy for co-delivery of drugs, tumor and metastatic lymph node targeting, and DOX resistance reversing in breast cancer chemotherapy.