RESUMEN
Achieving long-term (>3 months) colloidal stability of upconversion nanoparticles (UCNPs) in biologically relevant buffers has been a major challenge, which has severely limited practical implementation of UCNPs in bioimaging and nanomedicine applications. To address this challenge, nine unique copolymers formulations were prepared and evaluated as UCNP overcoatings. These polymers consisted of a poly(isobutylene-alt-maleic anhydride) (PIMA) backbone functionalized with different ratios and types of phosphonate anchoring groups and poly(ethylene glycol) (PEG) moieties. The syntheses were done as simple, one-pot nucleophilic addition reactions. These copolymers were subsequently coated onto NaYF4:Yb3+,Er3+ UCNPs, and colloidal stability was evaluated in 1 × PBS, 10 × PBS, and other buffers. UCNP colloidal stability improved (up to 4 months) when coated with copolymers containing greater proportions of anchoring groups and higher phosphonate valences. Furthermore, small molecules could be conjugated to these overcoated UCNPs by use of copper-free click chemistry, as was done to demonstrate suitability for sensor and bioprobe development.
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Nanopartículas , Organofosfonatos , Nanopartículas/química , Polietilenglicoles/química , Polímeros/química , Yoduro de PotasioRESUMEN
Multimodal therapeutic approach towards colorectal cancer (CRC) holds great promise. There is, however, no convincing strategy reported to date that employs a multimodal strategy in CRC treatment. The present study reports an intense green-emitting core-shell photoluminescent upconversion (CSGU) nanocrystal engineered to synergistically perform photodynamic and enzyme-triggered delivery of the chemotherapeutic agent for an enhanced therapeutic outcome on HT-29 colon carcinoma cells in vitro. The photodynamic activity is achieved by the energy transfer between CSGU and the chemically conjugated Rose Bengal (RB) molecules that are further protected by a mesoporous silica (MS) layer. The chemical assay demonstrates a remarkable FRET mediated generation of 1O2 under NIR (980 nm) excitation. The outermost MS layer of the nanoplatform is utilized for the loading of the 5FU anticancer drug, which is further capped with a guar gum (GG) polysaccharide polymer. The release of the 5FU is specifically triggered by the degradation of the GG cap by specific enzymes secreted from colonic microflora, which otherwise showed 'zero-release behavior' in the absence of any enzymatic trigger in various simulated gastro-intestinal (GI) conditions. Furthermore, the enhanced therapeutic efficacy of the nanoplatform (CSGUR-MSGG/5FU) was evaluated through in vitro studies using HT-29 CRC cell lines by various biochemical and microscopic assays by the simultaneous triggering effect of colonic enzyme and 980 nm laser excitation. In addition, the strong visible emission from the nanoplatform has been utilized for NIR-induced cellular bioimaging.
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Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Galactanos/química , Mananos/química , Gomas de Plantas/química , Rosa Bengala/administración & dosificación , Antimetabolitos Antineoplásicos/farmacología , Preparaciones de Acción Retardada/química , Fluorouracilo/farmacología , Células HT29 , Humanos , Rayos Infrarrojos , Nanocompuestos/química , Nanopartículas/química , Fotoquimioterapia , Rosa Bengala/farmacología , Dióxido de Silicio/químicaRESUMEN
Upconversion nanoparticles (UCNPs) are materials that provide unique advantages for biomedical applications. There are constantly emerging customized UCNPs with varying compositions, coatings, and upconversion mechanisms. Cellular uptake is a key parameter for the biological application of UCNPs. Uptake experiments have yielded highly varying results, and correlating trends between cellular uptake with different types of UCNP coatings remains challenging. In this report, the impact of surface polymer coatings on the formation of protein coronas and subsequent cellular uptake of UCNPs by macrophages and cancer cells was investigated. Luminescence confocal microscopy and elemental analysis techniques were used to evaluate the different coatings for internalization within cells. Pathway inhibitors were used to unravel the specific internalization mechanisms of polymer-coated UCNPs. Coatings were chosen as the most promising for colloidal stability, conjugation chemistry, and biomedical applications. PIMA-PEG (poly(isobutylene-alt-maleic) anhydride with polyethylene glycol)-coated UCNPs were found to have low cytotoxicity, low uptake by macrophages (when compared with PEI, poly(ethylenimine)), and sufficient uptake by tumor cells for surface-loaded drug delivery applications. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) studies revealed that PIMA-coated NPs were preferentially internalized by the clathrin- and caveolar-independent pathways, with a preference for clathrin-mediated uptake at longer time points. PMAO-PEG (poly(maleic anhydride-alt-1-octadecene) with polyethylene glycol)-coated UCNPs were internalized by energy-dependent pathways, while PAA- (poly(acrylic acid)) and PEI-coated NPs were internalized by multifactorial mechanisms of internalization. The results indicate that copolymers of PIMA-PEG coatings on UCNPs were well suited for the next-generation of biomedical applications.
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Nanopartículas , Corona de Proteínas , Corona de Proteínas/química , Corona de Proteínas/metabolismo , Humanos , Nanopartículas/química , Ratones , Animales , Células RAW 264.7 , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Polietilenglicoles/química , Polímeros/química , Propiedades de Superficie , Anhídridos Maleicos/química , Línea Celular Tumoral , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacologíaRESUMEN
Lanthanide-doped upconversion nanoparticles (UCNPs) possess the remarkable ability to convert multiple near-infrared (NIR) photons into higher energy ultraviolet-visible (UV-vis) photons, making them a prime candidate for several advanced applications within the realm of nanotechnology. Compared to traditional organic fluorophores and quantum dots (QDs), UCNPs possess narrower emission bands (fwhm of 10-50 nm), large anti-Stokes shifts, low toxicity, high chemical stability, and resistance to photobleaching and blinking. In addition, unlike UV-vis excitation, NIR excitation is nondestructive at lower power intensities and has high tissue penetration depths (up to 2 mm) with low autofluorescence and scattering. Together, these properties make UCNPs exceedingly favored for advanced bioanalytical and theranostic applications, where these systems have been well-explored. UCNPs are also well-suited for bioimaging, optically modulating chemistries, forensic science, and other state-of-the-art research applications. In this review, an up-to-date account of emerging applications in UCNP research, beyond bioanalytical and theranostics, are presented including optogenetics, super-resolution imaging, encoded barcodes, fingerprinting, NIR vision, UCNP-assisted photochemical manipulations, optical tweezers, 3D printing, lasing, NIR-II imaging, UCNP-molecule nanohybrids, and UCNP-based persistent luminescent nanocrystals.
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Elementos de la Serie de los Lantanoides , Nanopartículas , Puntos Cuánticos , Elementos de la Serie de los Lantanoides/química , Nanopartículas/química , Luminiscencia , Diagnóstico por ImagenRESUMEN
In an attempt to integrate photodynamic therapy (PDT) with photothermal therapy and chemotherapy for enhanced anticancer activity, we have rationally synthesized a multifunctional upconversion nanoplatform using NaYF4:Yb/Tm/Er/Fe nanoparticles (NPs) as the core and NaYbF4:1% Tm as a shell. The as-synthesized core-shell upconversion (CSU) NPs exhibited diverse and enhanced photoluminescence emissions in a wide range (UV to NIR) consequent upon Fe3+ doping in the core and fabrication of an active shell. Subsequently, CSU was first decorated with titania NPs as photosensitizers. Next, the mesoporous silica (MS) shell loaded with doxorubicin (DOX) via a photocleavable Ru complex as the gating molecule was developed around titania-containing CSU. Finally, gold nanorods (GNRs) with localized surface plasmon resonance (LSPR) at 800 nm were incorporated around the MS layer to obtain the multifunctional nanoplatform. We demonstrated that the UV, blue, and NIR emissions from the CSU produced ROS-mediated PDT through titania activation, induced DOX release through photocleavage of the Ru complex, and generated hyperthermia by LSPR activity of GNRs, respectively, upon a single NIR excitation through FRET. The therapeutic efficacy was validated on HeLa cell lines in vitro by various microscopic and biochemical studies under a significantly milder NIR irradiation and lower dosage of the nanoplatforms, which have been further demonstrated as diagnostic nanoprobes for cell imaging.
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Nanocompuestos/química , Fotoquimioterapia , Fototerapia , Antibióticos Antineoplásicos/síntesis química , Antibióticos Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Doxorrubicina/síntesis química , Doxorrubicina/química , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Oro/química , Células HeLa , Humanos , Rayos Infrarrojos , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/química , Tamaño de la Partícula , Porosidad , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Silicio/química , Propiedades de SuperficieRESUMEN
In the global context of increasing colonic diseases, colon specific oral drug delivery systems have shown promise as an effective therapeutic modality. Herein, we developed a mesoporous silica nanoparticle (MSN) based enzyme responsive materials for colon specific drug delivery. We have utilized guar gum, a natural carbohydrate polymer as a capping layer to contain a model drug, such as 5-flurouracil (5FU) within the mesoporous channels of MSN. Analytical characterization including electron microscopy, PXRD, nitrogen sorption, thermogravimetric analysis and FTIR, confirmed that the synthesized MSN with size less than 100nm is of MCM-41type. The studies further showed that the MSN maintained their discrete nanoparticle identity after guar gum capping through non-covalent interaction. The release of 5FU from guar gum capped MSN (GG-MSN) was specifically triggered via enzymatic biodegradation of guar gum by colonic enzymes in the simulated colonic microenvironment. Subsequently, the released drug manifested anticancer activity in colon cancer cell lines in vitro confirmed by flow cytometry and biochemical assay. The drug loaded GG-MSN system also demonstrated near perfect 'zero release' property in absence of enzymes in different simulated conditions of the gastrointestinal tract. Our study provides an important intermediate step to apply such GG-MSN based engineered nanomaterials for further detailed in vivo investigation.