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1.
Nanoscale ; 13(35): 14879-14899, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34533177

RESUMO

Colorectal cancer (CRC) has a poor prognosis and urgently needs better therapeutic approaches. 5-Aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) based photodynamic therapy (PDT) is already used in the clinic for several cancers but not yet well investigated for CRC. Currently, systemic administration of ALA offers a limited degree of tumour selectivity, except for intracranial tumours, limiting its wider use in the clinic. The combination of effective ALA-PDT and chemotherapy may provide a promising alternative approach for CRC treatment. Herein, theranostic Ag2S quantum dots (AS-2MPA) optically trackable in near-infrared (NIR), conjugated with endothelial growth factor receptor (EGFR) targeting Cetuximab (Cet) and loaded with ALA for PDT monotherapy or ALA/5-fluorouracil (5FU) for the combination therapy are proposed for enhanced treatment of EGFR(+) CRC. AS-2MPA-Cet exhibited excellent targeting of the high EGFR expressing cells and showed a strong intracellular signal for NIR optical detection in a comparative study performed on SW480, HCT116, and HT29 cells, which exhibit high, medium and low EGFR expression, respectively. Targeting provided enhanced uptake of the ALA loaded nanoparticles by strong EGFR expressing cells and formation of higher levels of PpIX. Cells also differ in their efficiency to convert ALA to PpIX, and SW480 was the best, followed by HT29, while HCT116 was determined as unsuitable for ALA-PDT. The therapeutic efficacy was evaluated in 2D cell cultures and 3D spheroids of SW480 and HT29 cells using AS-2MPA with either electrostatically loaded, hydrazone or amide linked ALA to achieve different levels of pH or enzyme sensitive release. Most effective phototoxicity was observed in SW480 cells using AS-2MPA-ALA-electrostatic-Cet due to enhanced uptake of the particles, fast ALA release and effective ALA-to-PpIX conversion. Targeted delivery reduced the effective ALA concentration significantly which was further reduced with codelivery of 5FU. Delivery of ALA via covalent linkages was also effective for PDT, but required a longer incubation time for the release of ALA in therapeutic doses. Phototoxicity was correlated with high levels of reactive oxygen species (ROS) and apoptotic/necrotic cell death. Hence, both AS-2MPA-ALA-Cet based PDT and AS-2MPA-ALA-Cet-5FU based chemo/PDT combination therapy coupled with strong NIR tracking of the nanoparticles demonstrate an exceptional therapeutic effect on CRC cells and excellent potential for synergistic multistage tumour targeting therapy.


Assuntos
Neoplasias Colorretais , Fotoquimioterapia , Pontos Quânticos , Ácido Aminolevulínico/farmacologia , Linhagem Celular Tumoral , Cetuximab/farmacologia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/tratamento farmacológico , Humanos , Imagem Óptica , Fármacos Fotossensibilizantes/farmacologia , Protoporfirinas
2.
Eur J Pharm Sci ; 157: 105639, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33188925

RESUMO

There is considerable interest in biomedical applications of quantum dot (QD) nanoparticles, in particular their use as imaging agents for diagnostic applications. In order to investigate the in vivo biodistribution and the potential toxicity of quantum dots (QDs), it is crucial to develop pharmacokinetic (PK) models as basis for prediction of QDs exposure profiles over time. Here, we investigated the in vivo biodistribution of novel indium-based QDs in mice for up to three months after intravenous administration and subsequently developed a translational population PK model to scale findings to humans. This evaluation was complemented by a comprehensive overview of the in vivo toxicology of QDs in rats. The QDs were primarily taken up by the liver and spleen and were excreted via hepatobiliary and urinary pathways. A non-linear mixed effects modelling approach was used to describe blood and organ disposition characteristics of QDs using a multi-compartment PK model. The observed blood and tissue exposure to QDs was characterised with an acceptable level of accuracy at short and long-term. Of note is the fast distribution of QDs from blood into liver and spleen in the first 24 h post-injection (half-life of 28 min) followed by a long elimination profile (half-life range: 47-90 days). This is the first study to assess the PK properties of QDs using a population pharmacokinetic approach to analyse in vivo preclinical data. No organ damage was observed following systemic administration of QDs at doses as high as 48 mg/kg at 24 h, 1 week and 5 weeks post-injection. In conjunction with the data arising from the toxicology experiments, PK parameter estimates provide insight into the potential PK properties of QDs in humans, which ultimately allow prediction of their disposition and enable optimisation of the design of first-in-human QDs studies.


Assuntos
Nanopartículas , Pontos Quânticos , Animais , Índio/toxicidade , Fígado , Camundongos , Pontos Quânticos/toxicidade , Ratos , Distribuição Tecidual
3.
Int J Mol Sci ; 21(9)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32366058

RESUMO

In this study we explored the efficacy of combining low dose photodynamic therapy using a porphyrin photosensitiser and dactinomycin, a commonly used chemotherapeutic agent. The studies were carried out on compressed collagen 3D constructs of two human ovarian cancer cell lines (SKOV3 and HEY) versus their monolayer counterparts. An amphiphilc photosensitiser was employed, disulfonated tetraphenylporphine, which is not a substrate for ABC efflux transporters that can mediate drug resistance. The combination treatment was shown to be effective in both monolayer and 3D constructs of both cell lines, causing a significant and synergistic reduction in cell viability. Compared to dactinomycin alone or PDT alone, higher cell kill was found using 2D monolayer culture vs. 3D culture for the same doses. In 3D culture, the combination therapy resulted in 10 and 22 times higher cell kill in SKOV3 and HEY cells at the highest light dose compared to dactinomycin monotherapy, and 2.2 and 5.5 times higher cell kill than PDT alone. The combination of low dose PDT and dactinomycin appears to be a promising way to repurpose dactinomycin and widen its therapeutic applications.


Assuntos
Antineoplásicos/farmacologia , Dactinomicina/farmacologia , Neoplasias Ovarianas/metabolismo , Fotoquimioterapia/métodos , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Feminino , Humanos
4.
Nanoscale ; 12(19): 10609-10622, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32373810

RESUMO

Cadmium-free quantum dots (QD) were combined with crystal violet photosensitising dye and incorporated into medical grade polyurethane via a non-covalent dipping process known as 'swell-encapsulation-shrink'. The antibacterial efficacy of the prepared quantum dot-crystal violet polyurethane substrates (QD + CV PU) was investigated under low power visible light illumination at similar intensities (500 lux) to those present in clinical settings. The antibacterial performance of QD + CV PU was superior to the constituent polymer substrates, eliminating ∼99.9% of an environmental P. aeruginosa strain, a clinical P. aeruginosa strain from a cystic fibrosis patient and a clinical E. coli strain. The nature of the reactive oxygen species (ROS) involved in antibacterial activity of the QD + CV PU surface was investigated using ROS inhibitors and time-resolved optical spectroscopy. The photo-physical interactions of the green-emitting QDs with CV lead to a combination of Type I and II electron transfer and energy transfer processes, with the highly potent ROS singlet oxygen playing a dominant role. This study is the first to demonstrate highly efficient synergistic killing of clinical and environmental strains of intrinsically resistant and multi-drug resistant Gram-negative bacteria using light-activated surfaces containing biocompatible cadmium-free QDs and crystal violet dye at ambient light levels.


Assuntos
Pontos Quânticos , Cádmio , Escherichia coli , Humanos , Polímeros
5.
ACS Appl Mater Interfaces ; 11(13): 12367-12378, 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30855136

RESUMO

The rising incidence of antibiotic-resistant infections from contaminated surfaces in hospitals or implanted medical devices has led to increasing interest in new antibacterial surfaces. Photoactivatable surfaces that can generate cytotoxic reactive oxygen species under exposure to ambient light is a promising approach to inactivation of surface-borne microorganisms. There is growing interest in the use of quantum dots (QDs) as light-harvesting agents for photobactericidal applications, but the cadmium in commonly used QDs will restrict clinical application. Herein, the photobactericidal activity of novel polyurethane substrates containing cadmium-free QDs was tested against clinical multidrug-resistant Gram-positive and Gram-negative bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA) and a carbapenemase-producing strain of Escherichia coli ( E. coli). To enhance the capacity for reactive oxygen species generation, QDs were incorporated into the polymer with a photosensitizing dye, crystal violet. Close proximity between the QD and dye enables electron and energy transfer processes leading to generation of cytotoxic singlet oxygen and superoxide radicals. A QD solution in cyclohexane was premixed with a solution of CV in the more polar solvent, dichloromethane, to promote the formation of QD-CV nanocomposite complexes via CV adsorption. This solution was then used to embed the QDs and crystal violet into medical grade polyurethane via swell-encapsulation. The combination of QD and CV elicited significant synergistic antibacterial activity under visible light against MRSA within 1 h (99.98% reduction) and E. coli within 4 h (99.96% reduction). Photoluminescence lifetime and singlet oxygen phosphorescence measurements demonstrated that interaction between the QDs and the crystal violet occurs within the polymer and leads to enhanced generation of reactive oxygen species. Strong inhibition of kill was observed using the superoxide scavenger, superoxide dismutase. The efficacy of these QD-CV polymer substrates, that can harvest light across the visible spectrum, against multidrug-resistant bacteria demonstrates the feasibility of this approach.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Violeta Genciana , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Pontos Quânticos/química , Antibacterianos/química , Antibacterianos/farmacologia , Cádmio , Violeta Genciana/química , Violeta Genciana/farmacologia
6.
Nanoscale ; 10(43): 20366-20376, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30376028

RESUMO

Endosomal entrapment is a key issue for the intracellular delivery of many nano-sized biotherapeutics to their cytosolic or nuclear targets. Photochemical internalisation (PCI) is a novel light-based solution that can be used to trigger the endosomal escape of a range of bioactive agents into the cytosol leading to improved efficacy in pre-clinical and clinical studies. PCI typically depends upon the endolysosomal colocalisation of the bioactive agent with a suitable photosensitiser that is administered separately. In this study we demonstrate that both these components may be combined for codelivery via a novel multifunctional liposomal nanocarrier, with a corresponding increase in the biological efficacy of the encapsulated agent. As proof of concept, we show here that the cytotoxicity of the 30 kDa protein toxin, saporin, in MC28 fibrosarcoma cells is significantly enhanced when delivered via a cell penetrating peptide (CPP)-modified liposome, with the CPP additionally functionalised with a photosensitiser that is targeted to endolysosomal membranes. This innovation opens the way for the efficient delivery of a range of biotherapeutics by the PCI approach, incorporating a clinically proven liposome delivery platform and using bioorthogonal ligation chemistries to append photosensitisers and peptides of choice.


Assuntos
Citosol/metabolismo , Citotoxinas/metabolismo , Lipossomos/química , Fármacos Fotossensibilizantes/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/química , Citotoxinas/química , Citotoxinas/farmacologia , Fibrossarcoma/metabolismo , Fibrossarcoma/patologia , Luz , Lipossomos/síntese química , Maleimidas/química , Microscopia Confocal , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/metabolismo , Ratos , Saporinas/química , Saporinas/metabolismo
7.
Br J Radiol ; 91(1092): 20180325, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30179039

RESUMO

A multi-disciplinary cooperative for nanoparticle-enhanced radiotherapy (NERT) has been formed to review the current status of the field and identify key stages towards translation. Supported by the Colorectal Cancer Healthcare Technologies Cooperative, the cooperative comprises a diverse cohort of key contributors along the translation pathway including academics of physics, cancer and radio-biology, chemistry, nanotechnology and clinical trials, clinicians, manufacturers, industry, standards laboratories, policy makers and patients. Our aim was to leverage our combined expertise to devise solutions towards a roadmap for translation and commercialisation of NERT, in order to focus research in the direction of clinical implementation, and streamline the critical pathway from basic science to the clinic. A recent meeting of the group identified barriers to and strategies for accelerated clinical translation. This commentary reports the cooperative's recommendations. Particular emphasis was given to more standardised and cohesive research methods, models and outputs, and reprioritised research drivers including patient quality of life following treatment. Nanoparticle design criteria were outlined to incorporate scalability of manufacture, understanding and optimisation of biological mechanisms of enhancement and in vivo fate of nanoparticles, as well as existing design criteria for physical and chemical enhancement. In addition, the group aims to establish a long-term and widespread international community to disseminate key findings and create a much-needed cohesive body of evidence necessary for commercial and clinical translation.


Assuntos
Nanopartículas , Radioterapia/métodos , Humanos
8.
Acta Biomater ; 81: 80-92, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30267880

RESUMO

Photochemical internalisation (PCI) is a method for enhancing delivery of drugs to their intracellular target sites of action. In this study we investigated the efficacy of PCI using a porphyrin photosensitiser and a cytotoxic agent on spheroid and non-spheroid compressed collagen 3D constructs of ovarian cancer versus conventional 2D culture. The therapeutic responses of two human carcinoma cell lines (SKOV3 and HEY) were compared using a range of assays including optical imaging. The treatment was shown to be effective in non-spheroid constructs of both cell lines causing a significant and synergistic reduction in cell viability measured at 48 or 96 h post-illumination. In the larger spheroid constructs, PCI was still effective but required higher saporin and photosensitiser doses. Moreover, in contrast to the 2D and non-spheroid experiments, where comparable efficacy was found for the two cell lines, HEY spheroid constructs were found to be more susceptible to PCI and a lower dose of saporin could be used. PCI treatment was observed to induce death principally by apoptosis in the 3D constructs compared to the mostly necrotic cell death caused by PDT. At low oxygen levels (1%) both PDT and PCI were significantly less effective in the constructs. STATEMENT OF SIGNIFICANCE: Assessment of new drugs or delivery systems for cancer therapy prior to conducting in vivo studies often relies on the use of conventional 2D cell culture, however 3D cancer constructs can provide more physiologically relevant information owing to their 3D architecture and the presence of an extracellular matrix. This study investigates the efficacy of Photochemical Internalisation mediated drug delivery in 3D constructs. In 3D cultures, both oxygen and drug delivery to the cells are limited by diffusion through the extracellular matrix unlike 2D models, and in our model we have used compressed collagen constructs where the density of collagen mimics physiological values. These 3D constructs are therefore well suited to studying drug delivery using PCI. Our study highlights the potential of these constructs for identifying differences in therapeutic response to PCI of two ovarian carcinoma lines.


Assuntos
Citotoxinas , Modelos Biológicos , Neoplasias Ovarianas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Piroptose/efeitos dos fármacos , Linhagem Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacocinética , Citotoxinas/farmacologia , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia
9.
Nanomedicine ; 14(8): 2644-2655, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30048815

RESUMO

Quantum dot (QD) nanoparticles are highly promising contrast agents and probes for biomedical applications owing to their excellent photophysical properties. However, toxicity concerns about commonly used cadmium-based QDs hinder their translation to clinical applications. In this study we describe the in vivo biodistribution and toxicology of indium-based water soluble QDs in rats following intravenous administration. The biodistribution measured at up to 90 days showed that QDs mainly accumulated in the liver and spleen, with similar elimination kinetics to subcutaneous administration. Evidence for QD degradation in the liver was found by comparing photoluminescence measurements versus elemental analysis. No organ damage or histopathological lesions were observed for the QDs treated rats after 24 h, 1 and 4 weeks following intravenous administration at 12.5 mg/kg or 50 mg/kg. Analysis of serum biochemistry and complete blood counts found no toxicity. This work supports the strong potential of indium-based QDs for translation into the clinic.


Assuntos
Cádmio , Índio/farmacocinética , Índio/toxicidade , Fígado/efeitos dos fármacos , Nanopartículas/toxicidade , Pontos Quânticos/toxicidade , Animais , Feminino , Fígado/metabolismo , Modelos Animais , Nanopartículas/metabolismo , Pontos Quânticos/metabolismo , Ratos , Distribuição Tecidual , Testes de Toxicidade
10.
Nanoscale ; 10(4): 1570-1581, 2018 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-29308480

RESUMO

Photodynamic therapy (PDT) is the subject of considerable research in experimental cancer models mainly for the treatment of solid cancerous tumours. Recent studies on the use of nanoparticles as photosensitiser carriers have demonstrated improved PDT efficacy in experimental cancer therapy. Experiments typically employ conventional monolayer cell culture but there is increasing interest in testing PDT using three dimensional (3D) cancer models. 3D cancer models can better mimic in vivo models than 2D cultures by for example enabling cancer cell interactions with a surrounding extracellular matrix which should enable the treatment to be optimised prior to in vivo studies. The aim of this review is to discuss recent research using PDT in different types of 3D cancer models, from spheroids to nano-fibrous scaffolds, using a range of photosensitisers on their own or incorporated in nanoparticles and nanodelivery systems.


Assuntos
Técnicas de Cultura de Células , Sistemas de Liberação de Medicamentos , Nanoestruturas , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Matriz Extracelular , Humanos , Fármacos Fotossensibilizantes/administração & dosagem
11.
Sci Rep ; 7(1): 6059, 2017 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-28729656

RESUMO

A major problem with many promising nano-sized biotherapeutics including macromolecules is that owing to their size they are subject to cellular uptake via endocytosis, and become entrapped and then degraded within endolysosomes, which can significantly impair their therapeutic efficacy. Photochemical internalisation (PCI) is a technique for inducing cytosolic release of the entrapped agents that harnesses sub-lethal photodynamic therapy (PDT) using a photosensitiser that localises in endolysosomal membranes. Using light to trigger reactive oxygen species-mediated rupture of the photosensitised endolysosomal membranes, the spatio-temporal selectivity of PCI then enables cytosolic release of the agents at the selected time after administration so that they can reach their intracellular targets. However, conventional photosensitisers used clinically for PDT are ineffective for photochemical internalisation owing to their sub-optimal intracellular localisation. In this work we demonstrate that such a photosensitiser, chlorin e6, can be repurposed for PCI by conjugating the chlorin to a cell penetrating peptide, using bioorthogonal ligation chemistry. The peptide conjugation enables targeting of endosomal membranes so that light-triggered cytosolic release of an entrapped nano-sized cytotoxin can be achieved with consequent improvement in cytotoxicity. The photoproperties of the chlorin moiety are also conserved, with comparable singlet oxygen quantum yields found to the free chlorin.


Assuntos
Endossomos/metabolismo , Lisossomos/metabolismo , Porfirinas/farmacologia , Animais , Biomarcadores , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Humanos , Estrutura Molecular , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Transporte Proteico , Ratos
12.
Biomaterials ; 104: 182-91, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27454064

RESUMO

Quantum dots (QDs) are attractive photoluminescence probes for biomedical imaging due to their unique photophysical properties. However, the potential toxicity of QDs has remained a major obstacle to their clinical use because they commonly incorporate the toxic heavy metal cadmium within the core of the QDs. In this work, we have evaluated a novel type of heavy metal-free/cadmium-free and biocompatible QD nanoparticles (bio CFQD(®) nanoparticles) with a good photoluminescence quantum yield. Sentinel lymph node mapping is an increasingly important treatment option in the management of breast cancer. We have demonstrated their potential for lymph node mapping by ex vivo imaging of regional lymph nodes after subcutaneous injection in the paw of rats. Using photoluminescence imaging and chemical extraction measurements based on elemental analysis by inductively coupled plasma mass spectroscopy, the quantum dots are shown to accumulate quickly and selectively in the axillary and thoracic regional lymph nodes. In addition, lifetime imaging microscopy of the QD photoluminescence indicates minimal perturbation to their photoluminescence properties in biological systems.


Assuntos
Medições Luminescentes/métodos , Nanopartículas Metálicas/química , Pontos Quânticos/química , Linfonodo Sentinela/química , Linfonodo Sentinela/patologia , Animais , Feminino , Índio/química , Metais Pesados , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual
13.
Small ; 10(24): 5106-15, 2014 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-25164061

RESUMO

Photocatalytic generation of reactive oxygen species (ROS) from quantum dots (QDs) has been widely reported yet quantitative studies of ROS formation and their quantum yields are lacking. This study investigates the generation of ROS by water soluble PEGylated CdSe/ZnS QDs with red emission. PEGylation of QDs is commonly used to confer water solubility and minimise uptake by organs of the reticuloendothelial system; therefore studies of ROS formation are of biomedical relevance. Using non-photolytic visible wavelength excitation, the superoxide anion radical is shown to be the primary ROS species generated with a quantum efficiency of 0.35%. The yield can be significantly enhanced in the presence of the electron donor, nicotinamide adenine dinucleotide (NADH), as demonstrated by oxygen consumption measurements and electron paramagnetic resonance spectroscopy with in situ illumination. Direct production of singlet oxygen is not detectable from the QDs alone. A comparison is made with ROS generation by the same QDs complexed with a sulfonated phthalocyanine which can generate singlet oxygen via Förster resonance energy transfer between the QDs and the phthalocyanine.


Assuntos
Luz , Polietilenoglicóis/química , Pontos Quânticos , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Consumo de Oxigênio
14.
Small ; 10(4): 782-92, 2014 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-24031023

RESUMO

The interaction of Tat-conjugated PEGylated CdSe/ZnS quantum dots (QD) with the amphiphilic disulfonated aluminium phthalocyanine photosensitiser is investigated in aqueous solution and in a human breast cancer cell line. In aqueous solution, the QDs and phthalocyanine form stable nanocomposites. Using steady-state and time-resolved fluorescence measurements combined with singlet oxygen detection, efficient Förster resonance energy transfer (FRET) is observed with the QDs acting as donors, and the phthalocyanine photosensitiser, which mediates production of singlet oxygen, as acceptors. In cells, the Tat-conjugated QDs localise in lysosomes and the QD fluorescence lifetimes are close to values observed in aqueous solution. Strong FRET-induced quenching of the QD lifetime is observed in cells incubated with the nanocomposites using fluorescence lifetime imaging microscopy (FLIM). Using excitation of the QDs at wavelengths where phthalocyanine absorption is negligible, FRET-induced release of QDs from endo/lysosomes is confirmed using confocal imaging and FLIM, which is attributed to photooxidative damage to the endo/lysosomal membranes mediated by the phthalocyanine acceptor.


Assuntos
Transferência Ressonante de Energia de Fluorescência/métodos , Indóis/farmacologia , Espaço Intracelular/metabolismo , Nanopartículas/química , Imagem Óptica/métodos , Fármacos Fotossensibilizantes/farmacologia , Pontos Quânticos/metabolismo , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Humanos , Células MCF-7 , Microscopia de Fluorescência
15.
Nanoscale ; 5(13): 6106-16, 2013 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-23728482

RESUMO

PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data suggest the interference of the stealth-conferring layer (PEG) with small targeting agents, but not with bulky antibodies. Moreover, we showed that selective photokilling of tumour cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Siloxanas , Anticorpos Antineoplásicos/química , Anticorpos Antineoplásicos/farmacologia , Receptores ErbB/antagonistas & inibidores , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Siloxanas/química , Siloxanas/farmacologia
16.
Nanomedicine (Lond) ; 4(3): 353-63, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19331542

RESUMO

Semiconductor quantum dots have received considerable interest in recent years as a result of their unique optical properties, leading to many applications in biology. This review examines their potential for photosensitization in photodynamic therapy compared with, and in combination with, conventional photosensitizing organic dyes. Photodynamic therapy is used for treating a range of malignant tumors and certain non-malignant pathologies, and conventional photosensitizers are based on organic dyes that are efficient generators of cytotoxic reactive oxygen species. By exploiting the unique optical properties of quantum dots, the conjugation of quantum dots with photosensitizers and targeting agents could provide a new class of versatile multifunctional nanoparticles for both diagnostic imaging and therapeutic applications.


Assuntos
Nanomedicina , Fotoquimioterapia/métodos , Pontos Quânticos , Diagnóstico por Imagem/métodos , Humanos , Nanomedicina/métodos , Nanomedicina/tendências , Fotoquimioterapia/tendências , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
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