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1.
Pharm Res ; 37(8): 162, 2020 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-32749542

RESUMEN

PURPOSE: The goal of this study was to develop chemotherapeutic drug-loaded photoactivable stealth polymer-coated silica based- mesoporous titania nanoplatforms for enhanced antitumor activity. METHODS: Both in vitro and in vivo models of solvothermal treated photoactivable nanoplatforms were evaluated for efficient chemo-photothermal activity. A versatile nanocomposite that combined silica based- mesoporous titania nanocarriers (S-MTN) with the promising photoactivable agent, graphene oxide (G) modified with a stealth polymer (P) was fabricated to deliver chemotherapeutic agent, imatinib (I), (referred as S-MTN@IG-P) for near-infrared (NIR)-triggered drug delivery and enhanced chemo-photothermal therapy. RESULTS: The fabricated S-MTN@IG-P nanoplatform showed higher drug loading (~20%) and increased drug release (~60%) in response to light in acidic condition (pH 5.0). As prepared nanoplatform significantly converted NIR light into thermal energy (43.2°C) to produce reactive oxygen species (ROS). The pronounced cytotoxic effect was seen in both colon cancer cells (HCT-116 and HT-29) that was mediated through the chemotherapeutic effect of imatinib and the photothermal and ROS generation effects of graphene oxide. In vivo study also showed that S-MTN@IG-P could significantly accumulate into the tumor area and suppress the tumor growth under NIR irradiation without any biocompatibility issues. CONCLUSION: Cumulatively, the above results showed promising effects of S-MTN@IG-P for effective chemo-phototherapy of colon cancer.


Asunto(s)
Antineoplásicos/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Nanopartículas/química , Nanopartículas/uso terapéutico , Fotoquimioterapia/métodos , Titanio/química , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Portadores de Fármacos/química , Liberación de Fármacos , Células HCT116 , Células HT29 , Humanos , Mesilato de Imatinib/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Especies Reactivas de Oxígeno , Dióxido de Silicio
2.
J Control Release ; 346: 1-19, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35398173

RESUMEN

Parkinson's disease (PD) is a debilitating neurodegenerative condition characterized by the loss of dopaminergic neurons within the substantia nigra. The specific molecular mechanisms through which PD-associated neuronal loss occurs remain unclear, and there is no available effective treatment against PD-related neurodegeneration. Resveratrol (RSV) has exhibited promising neuroprotective effects via antioxidant and anti-inflammatory activity. However, its poor bioavailability in the brain represents a challenge for its application in PD treatment. In this study, we synthesized RSV-loaded PLGA nanoparticles (RSV-PLGA-NPs) conjugated with lactoferrin (Lf) to enhance RSV diffusion into the brain and assessed whether this formulation improved the neuroprotective effects of RSV in experimental PD models. The Lf-conjugated RSV-PLGA-NPs (Lf-RSV-PLGA-NPs) exhibited enhanced internalization into SH-SY5Y and human brain microvascular endothelial cells as compared to RSV-PLGA-NPs and free RSV. Further, Lf-RSV-PLGA-NPs were more effective than RSV-PLGA-NPs and free RSV in attenuating the MPP+-induced generation of reactive oxygen species, reduction of mitochondrial membrane potential, and cell death. Importantly, Lf conjugation specifically increased the accumulation of RSV-PLGA-NPs in the brain as determined via bioluminescent imaging analyses. Our formulation substantially enhanced the neuroprotective effects of RSV in the MPTP-induced PD model. Hence, Lf-RSV-PLGA-NPs represent a promising tool for improving RSV bioavailability and neuroprotection within the brain.


Asunto(s)
Nanopartículas , Neuroblastoma , Fármacos Neuroprotectores , Enfermedad de Parkinson , Barrera Hematoencefálica , Células Endoteliales , Humanos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Resveratrol
3.
Biomaterials ; 284: 121511, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35398587

RESUMEN

The significant advances in nano-drug delivery systems (NDDS) for anticancer agents have led to the development of computational techniques, such as machine learning and neural networks to identify the optimal architectural and compositional design in a wide variety of therapeutic nanoformulations. On the other hand, few studies have examined downsized plug-in reaction-ware embodied in an autonomous platform for the instant reconfigurable production of engineered nanomaterials to guide optimal NDDS designs and delivery strategies. This paper describes an on-demand system for an electrically operable, continuously processible material produced by sequential spray pyrolysis and vibrating spray for single-pass NDDS assembly. In particular, a mild chemotherapeutic NDDS consisting of amorphous boron nitride (a-BN; a stable base material for loading), doxorubicin (DOX; an anticancer drug), and folic acid-chitosan conjugate (FACHI; a targeting and antiopsonic agent), called a-BN-DOX@FACHI, was fabricated using the developed system. a-BN-DOX@FACHI was assessed for the pH-responsive release of DOX, targeting of the folate receptor, and its resistance to opsonization and macrophage phagocytosis. a-BN-DOX@FACHI was found to be a mild cancer chemotherapeutic with reasonable biosafety. Integrating a metal ablation device with the developed on-demand system enabled the reconfiguration of NDDS from a-BN-DOX@FACHI to a-BN-Au-DOX@FACHI or a-BN-Pt-cisplatin@bovine serum albumin to add a photothermal effect with a range of architectures and compositions.


Asunto(s)
Antineoplásicos , Sistemas de Liberación de Medicamentos , Aerosoles , Antineoplásicos/farmacología , Línea Celular Tumoral , Doxorrubicina/farmacología , Portadores de Fármacos , Sistemas de Liberación de Medicamentos/métodos , Sistema de Administración de Fármacos con Nanopartículas
4.
J Control Release ; 329: 645-664, 2021 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-33022330

RESUMEN

Tumor-associated macrophages (TAM) constitute up to 50-80% of stromal cells in breast cancer (BC), and are correlated with poor prognosis. As epidermal growth factor receptor (EGFR) is overexpressed in 60-80% of patients with triple negative breast cancer (TNBC), photoimmunotherapy (PIT) with cetuximab-targeted gold nanorods (CTX-AuNR) is an attractive therapeutic strategy for TNBC. The 3D cell culture model can mimic drug resistance conferred by the tumor microenvironment and its 3D organization; therefore, TAM and non-TAM embedded TNBC spheroids were constructed to evaluate the therapeutic efficacy of CTX-AuNR plus near infrared (NIR) irradiation. Cytotoxicity, reactive oxygen species (ROS) generation, and protein expression were compared in TNBC (± TAM) spheroids. The IC50 values of doxorubicin (DOX) in TAM-embedded TNBC spheroids were significantly higher than those in TNBC spheroids, demonstrating drug resistance, which could be explained by activation of IL-10/IL-10 receptor/STAT3/Bcl-2 signaling. However, 3D in vitro and in vivo results demonstrated that the efficacy of CTX-AuNR plus NIR irradiation was not significantly different in (± TAM) embedded TNBC cells. By enhancing ROS generation, CTX-AuNR plus NIR irradiation reprogrammed TAM polarization to the M1 anti-tumor phenotype, as indicated by macrophage mannose receptor (MMR) downregulation. Thus, CTX-AuNR plus NIR can serve as a potent PIT strategy for treating EGFR-overexpressing TNBC cells.


Asunto(s)
Nanotubos , Neoplasias de la Mama Triple Negativas , Línea Celular Tumoral , Cetuximab , Resistencia a Medicamentos , Oro , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Microambiente Tumoral , Macrófagos Asociados a Tumores
5.
Int J Pharm ; 582: 119330, 2020 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-32298743

RESUMEN

The hindrances in achieving clinically translatable anticancer platforms are being tackled through nanotechnology-based formulations. In this study, stimuli-responsive, phytoactive constituent-loaded nanophytoliposomes were fabricated for designing a specific antitumor platform. Ursolic acid (UA)-loaded nanophytoliposomes (UA-PLL-HA.P) enwrapped in a poly-L-lysine (PLL) coat and hyaluronic acid (HA) were nanosized; these nanophytoliposomes had spherical morphology, slightly negative charge, and an in-range polydispersity index (~0.25). Successful fabrication of the nanosystem was proven through several characterization methods and the pH- and enzyme-responsiveness of the nanosystem was assessed through a release study. The cellular internalization in CD44 receptor-expressing cell lines was amplified by enhanced permeation and retention as well as by active targeting. In vitro antitumor behavior was confirmed through in vitro cytotoxic and apoptotic activity of the nanosystem. Similarly, in vivo imaging showed exceptional biodistribution in the tumor in agreement with the in vitro findings. Moreover, the tumor inhibitory rate of UA-PLL-HA.P was significantly higher, and was ascribed to the targeting potential and stimuli-responsiveness. In summary, UA-PLL-HA.P exhibited pronounced anticancer effect and could open a number of possibilities for discovering novel phytoconstituent-incorporated nanoformulations.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Ácido Hialurónico/química , Nanopartículas , Neoplasias/tratamiento farmacológico , Polilisina/química , Polímeros de Estímulo Receptivo/química , Triterpenos/farmacología , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Composición de Medicamentos , Liberación de Fármacos , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Liposomas , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias/metabolismo , Neoplasias/patología , Distribución Tisular , Triterpenos/química , Triterpenos/metabolismo , Ácido Ursólico
6.
Carbohydr Polym ; 249: 116815, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-32933663

RESUMEN

Hyaluronic acid (HA) assisted effective internalization into CD44 receptor-overexpressing cancer cells, which could offer an excellent cytotoxic profile and tumor alterations. In this study, duo-photothermal agents (copper sulfide (CuS) and graphene oxide (GO)), chemotherapeutic drug (doxorubicin (DOX)), and targeting moiety (HA) were incorporated into a complexed nanoconstruct for trio-responsive chemo-phototherapy. The nanosystem (CuS(DOX)-GO-HA) was demonstrating its responsive drug release and escalated photothermal behavior. The hyperthermia and photodynamic effect were observed along with efficient ROS generation in the presence of dual photosensitizers. The in vivo biodistribution and photothermal profile reflected a high accumulation and retention of the nanoconstruct in the tumor. Importantly, nanoconstructs effectively inhibit tumor growth based on tumor volume analysis and the altered expression of apoptosis, cell proliferation, and angiogenesis markers. Collectively, these findings suggest that this nanoconstruct has excellent antitumor effects in CD44 overexpressed cells showing the potential for clinical translation in the future.


Asunto(s)
Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/terapia , Carcinoma de Células Escamosas/terapia , Doxorrubicina/farmacología , Ácido Hialurónico/administración & dosificación , Nanopartículas/administración & dosificación , Fotoquimioterapia , Animales , Antibióticos Antineoplásicos/química , Apoptosis , Neoplasias de la Mama/patología , Carcinoma de Células Escamosas/patología , Proliferación Celular , Terapia Combinada , Cobre/química , Doxorrubicina/química , Femenino , Grafito/química , Humanos , Ácido Hialurónico/química , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/química , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
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