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The infectious diseases resulting from pathogenic microbes are highly contagious and the source of infection is difficult to control, which seriously endangers life and public health safety. Although the emergence of antibiotics has a good therapeutic effect in the early stage, the massive abuse of antibiotics has brought about the evolution of pathogens with drug resistance, which has gradually weakened the lethality and availability of antibiotics. Cancer is a more serious disease than pathogenic bacteria infection, which also threatens human life and health. Traditional treatment methods have limitations such as easy recurrence, poor prognosis, many side effects, and high toxicity. These two issues have led to the exploration and development of novel therapeutic agents (such as conjugated polymers) and therapeutic strategies (such as phototherapy) to avoid the increase of drug resistance and toxic side effects. As a class of organic polymer biological functional materials with excellent photoelectric properties, Conjugated polymers (CPs) have been extensively investigated in biomedical fields, such as the detection and treatment of pathogens and tumors due to their advantages of easy modification and functionalization, good biocompatibility and low cost. A rare comprehensive overview of CPs-based detection and treatment applications has been reported. This paper reviews the design strategies and research status of CPs used in biomedicine in recent years, introduces and discusses the latest progress of their application in the detection and treatment of pathogenic microorganisms and tumors according to different detection or treatment methods, as well as the limitations and potential challenges in prospective exploration.
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Pathogenic microorganisms have been a serious threat to human life and have become a public health problem of global concern. However, in the actual treatment there is a lack of efficient antimicrobial strategies which do not easily develop drug resistance; this can lead to inaccurate drug treatment that worsens the infection and even threatens life. With the emergence of a variety of drug-resistant bacteria and fungi, photodynamic therapy has gradually become one of the most promising treatment methods for drug-resistant bacteria infection; this is because it is controllable, non-invasive, and not prone to cause the development of drug resistance. Organic conjugated polymers that possess high fluorescence intensity, a large molar extinction coefficient, excellent light stability, an adjustable energy band, easy modification, good biocompatibility, and the ability to photosensitize oxygen to produce reactive oxygen species have been widely used in the fields of solar cells, highly sensitive detection systems, biological imaging, and anti-cancer and anti-microbial treatment. Photodynamic therapy is non-invasive and has high temporal and spatial resolution and is a highly effective antimicrobial treatment that does not easily induce drug resistance; it has also stimulated the scientific research enthusiasm of researchers and has become a research hotspot in the antimicrobial field. In this review, the photodynamic antibacterial applications of conjugated polymers with different structure types are summarized, and their development directions are considered.
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In recent years, photodynamic therapy (PDT) has become one of the important therapeutic methods for treating cancer. Aggregation-induced emission (AIE) photosensitizers (PSs) overcome the aggregation-caused quenching (ACQ) effects of conventional PSs in aggregation or high concentration states, showing enhanced reactive oxygen species (ROS) generating capacity and improved therapeutic efficiency. Meanwhile, connecting different donor and acceptor groups gives the PSs a lower energy level and the absorption/emission of a long wavelength, which makes the PSs produce more ROS and penetrate deeper into the tissue for imaging. As a promising tool for achieving efficient PDT applications, numerous studies have demonstrated the advantages and potential medical applications of AIE PSs in the diagnosis and treatment of various diseases. Herein, we outline the research progress of AIE PSs with different representative structures in fluorescence imaging and photodynamic anti-tumor therapy, and expound the design strategy of the donor-acceptor (D-A) framework for constructing practical AIE PSs in the past three years. Furthermore, this review addresses the underlying challenges and opportunities of AIE PSs in PDT, aiming to grasp the striving directions of the next generation of AIE PSs.
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Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de OxigênioRESUMO
Glioblastoma is the most common primary brain cancer and it is nearly impossible to remove the entire tumor with surgery or a single drug. EGFRvIII is the most frequent genetic change associated with glioblastoma, so EGFRvIII-based targeting therapies provide promise for treating glioblastoma. Herein, poly[2-methoxy-5-(2'-ethylhexyloxy)-p-phenylenevinylene] (PPV) was used as the core to prepare a conjugated polymer nanoparticle (PPVN) modified with anti-EGFRvIII (PPVN-A) that exhibited high ROS generation ability under white light irradiation. PPVN-A could target EGFRvIII-overexpressed tumor cells and damaged more than 90% of tumor cells with the light illumination while PPVN without modification exhibited no obvious cytotoxicity toward these cells under the same condition. Thus, the photodynamic treatment of glioblastoma cells using PPVN-A could be achieved, indicating the potential of anti-EGFRvIII-modified nanoparticles as a therapeutic material for treating glioblastoma in clinic.
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Neoplasias Encefálicas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Nanopartículas/química , Polivinil/química , Neoplasias Encefálicas/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Glioblastoma/metabolismo , Células HEK293 , Humanos , Polímeros/químicaRESUMO
The synthesis of superparamagnetic nanoclusters is critical for ultra-sensitive magnetic resonance imaging (MRI). Herein, we describe the synthesis of water-soluble, biocompatible and superparamagnetic gadolinium-doped iron oxide nanoclusters (GdIO NCs) via a one-pot reaction by thermal decomposition of ferric oleate and gadolinium oleate precursors with α,ω-dicarboxyl poly(ethylene glycol) as a surfactant. The resulting water-dispersible GdIO NCs possess good stability and monodispersity with narrow size distribution, and exhibit superparamagnetic behaviors. We also explored the effect of gadolinium doping amounts on the magnetic properties and longitudinal (r1) and transverse relaxivity (r2) of the nanoclusters. In addition, the GdIO NCs can be functionalized with fluorescein isothiocyanate (FITC) while maintaining their magnetic properties and biocompatibility. The GdIO NCs and FITC conjugated NCs were preliminarily evaluated as MRI and fluorescent probes. The results show that the GdIO NCs provide an important nano-platform for theranostics with non-invasive MRI and optical monitoring capabilities.
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Materiais Biocompatíveis/síntese química , Compostos Férricos/química , Gadolínio/química , Nanopartículas/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Compostos Férricos/farmacologia , Gadolínio/farmacologia , Humanos , Imageamento por Ressonância Magnética , Tamanho da Partícula , Solubilidade , Propriedades de Superfície , Células Tumorais Cultivadas , Água/químicaRESUMO
The T1-T2 dual-mode contrast agents for magnetic resonance imaging (MRI) can generate self-complementary confirmed T2 and T1 images, hence greatly improving the reliability. Facilely synthesizing nanoparticles with the ultrasensitive contrast property remains extremely challenging in nanoscience. Moreover, uncovering the mechanism correlating the signal enhancements and chemical constituents is vital for designing novel efficient synergistically enhanced T1-T2 dual-mode MRI nanoprobes. Herein, we report a one-pot facile method to synthesize the superparamagnetic manganese oxide-doped iron oxide (Fe3O4/MnO) nanoparticles for T1-T2 dual-mode MR imaging. Under external magnetic field, the local magnetic field intensities of MnO and Fe3O4 could be simultaneously enhanced through embedding MnO into Fe3O4 nanoparticles and hence can cause synergistic T1 and T2 contrast enhancements. Moreover, a novel and facile cost-effective method for large-scale synthesis of hydroxyl-polyethylene glycol-phosphonic acid-stabilizing ligands is designed. The facile synthetic method and surface coating strategy of superparamagnetic Fe3O4/MnO nanoparticles offer an idea for the chemical design and preparation of superparamagnetic nanoparticles with ultrasensitive MRI contrast abilities for disease evaluation and treatment.
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Antioxidantes/farmacologia , Melaninas/metabolismo , Pigmentação da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , alfa-Tocoferol/farmacologia , Animais , Antioxidantes/síntese química , Linhagem Celular Tumoral , Ensaios Enzimáticos , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Polietilenoglicóis/química , Pele/metabolismo , alfa-Tocoferol/análogos & derivados , alfa-Tocoferol/síntese químicaRESUMO
In this work, a series of nanoparticles were prepared assembled by a highly emissive solid-state organoboron-based stilbene (OBS) and PS-PEG-COOH via regulating the ratio of these two compounds using a co-precipitation method. The resultant OBS nanoparticles (OBSNs) were homogeneously dispersed in water media with average sizes of 36-82 nm and exhibited large Stokes shift, high fluorescence quantum yield, excellent photostability and low cytotoxicity. These organic nanoparticles could be internalized by MCF-7 cells and could accumulate in the cytoplasm outside the organelles. In addition, it is found that the nanoparticles with least negative charge and moderate size are most easily internalized by cells. Furthermore, the internalized nanoparticles could be retained inside the live cells for a long time and could be uniformly separated into two cells after the cell division process, permitting long-term cellular imaging applications.
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A new glucose-driven photodynamic antimicrobial system was developed to efficiently kill bacteria and fungi, taking advantage of organic-inorganic network materials encapsulating glucose oxidase and horseradish peroxidase and bioluminescence resonance energy transfer (BRET).
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Anti-Infecciosos/administração & dosagem , Gadolínio/química , Glucose Oxidase/administração & dosagem , Glucose/metabolismo , Peroxidase do Rábano Silvestre/administração & dosagem , Peróxido de Hidrogênio/metabolismo , Compostos Organometálicos/química , Monofosfato de Adenosina/metabolismo , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Glucose Oxidase/farmacologia , Peroxidase do Rábano Silvestre/farmacologia , Humanos , Luz , Luminescência , Modelos Moleculares , FotoquimioterapiaRESUMO
The outstanding optical properties and biocompatibility of fluorescent conjugated polymer nanoparticles (CPNs) make them favorable for bioimaging application. However, few CPNs could achieve stable cell membrane labeling due to cell endocytosis. In this work, conjugated polymer nanoparticles (PFPNP-PLE) encapsulated with PFP and PLGA-PEG-N3 in the matrix and functionalized with the small-molecule drug plerixafor (PLE) on the surface were prepared by a mini-emulsion method. PFPNP-PLE exhibits excellent photophysical properties, low cytotoxicity, and specific cytomembrane location, which makes it a potential cell membrane labeling reagent with blue fluorescence emission, an important component for multilabel/multicolor bioimaging.
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Membrana Celular/metabolismo , Nanopartículas/química , Polímeros/química , Benzilaminas , Membrana Celular/química , Ciclamos , Portadores de Fármacos/química , Endocitose , Corantes Fluorescentes/química , Células HT29 , Células HeLa , Compostos Heterocíclicos/química , Humanos , Células MCF-7 , Microscopia de Fluorescência , Polietilenoglicóis/química , Poliglactina 910/química , Propriedades de SuperfícieRESUMO
An unconventional strategy that can be temporally and remotely activated with light to combat the drug resistance of cancer cells is developed. A cell-membrane-anchored photosensitizer (OPV) is used to enhance anticancer drug uptake and restore toxicity in resistant cancer cells. This method recovers the activity of the already established anticancer drugs, and provides a new strategy for the development of light manipulation to combat anticancer resistance.
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Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Polivinil/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Cátions/química , Permeabilidade da Membrana Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta a Droga , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Humanos , Luz , Células MCF-7 , Microscopia Confocal , Polivinil/química , Polivinil/farmacocinéticaRESUMO
In this work, a new multifunctional assembled hydrogel was prepared by incorporating gadolinium ions (Gd(3+)) with salmon-sperm DNA and polythiophene derivative (PT-COOH) through chelation interactions. Efficient energy transfer from PT-COOH to Gd(3+) ions takes place followed by sensitization of oxygen molecule to generate reactive oxygen species (ROS) under light irradiation. Cancer cells can be encapsulated into the hydrogel in situ as the formation of hydrogel followed by killing by the ROS. Integration of imaging modality with therapeutic function within a single assembled hydrogel is therefore anticipated to be a new and challenging design element for new hydrogel materials.
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DNA/química , Hidrogéis/química , Neoplasias/terapia , Animais , Materiais Biocompatíveis/química , Cátions , Quelantes/química , Reagentes de Ligações Cruzadas/química , Gadolínio/química , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Células Jurkat , Microscopia Eletrônica de Varredura , Oxigênio/química , Espécies Reativas de Oxigênio/química , Salmão , Tiofenos/químicaRESUMO
Conjugated polymers (CPs) attract a lot of attention in sensing, imaging, and biomedical applications because of recent achievements that are highlighted in this Research News article. A brief review of recent progress in the application of CP-based energy-transfer systems in antimicrobial and anticancer treatments is provided. The transfer of excitation energy from CPs to photosensitizers leads to the generation of reactive oxygen species (ROS) that are able to efficiently kill pathogenic microorganisms and cancer cells in the surroundings. Both fluorescence resonance energy transfer (FRET) and bioluminescence energy transfer (BRET) modes are discussed.
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Anti-Infecciosos/química , Antineoplásicos/química , Transferência de Energia , Polímeros/química , Animais , Fármacos Fotossensibilizantes/químicaRESUMO
Using cell-surface modification and biotin-streptavidin interactions, immune cells and target tumor cells are made to form multicellular assemblies. A polythiophene derivative can undergo cellular uptake, allowing the sensitization of oxygen under light irradiation. The subsequent generation of reactive oxygen species (ROS) regulates cell-cell communication in time and space.
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Comunicação Celular/fisiologia , Células Matadoras Naturais/citologia , Luz , Polímeros/química , Biotina/química , Biotina/metabolismo , Humanos , Células Jurkat , Células Matadoras Naturais/imunologia , Microscopia Confocal , Ligação Proteica , Estreptavidina/química , Estreptavidina/metabolismo , Tiofenos/químicaRESUMO
In the past few years, conjugated polymer nanoparticles (CPNs) have been successfully prepared and applied in the biological field because of their unique opto-electronic properties. The rapid development of CPNs is mainly attributed to their simple synthesis procedures and easy separation steps. The advantages of CPNs include high brightness, excellent photostability, low cytotoxicity, high quantum yield and versatile surface modification. The functionalization of CPNs with specific recognition elements imparts them good ability for targeted recognition and imaging in vitro and in vivo. CPNs can be applied to deliver drug and gene, and simultaneously to real-time monitor the release process due to their self-luminous characteristics. Moreover, CPNs can sensitize oxygen molecules to generate reactive oxygen species (ROS) which can kill adjacent bacteria and tumor cells. In this tutorial review, we provide a recent development of the preparation methods, properties, and functionalization strategies of CPNs, especially discussing their biological applications in targeted imaging, drug/gene delivery and biomedicine. The challenges and outlooks in this field will also be discussed.
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Nanopartículas/química , Polímeros/química , Animais , Encéfalo/patologia , Portadores de Fármacos/química , Emulsões/química , Humanos , Microscopia Confocal , Neoplasias/diagnóstico , Neoplasias/patologiaRESUMO
For most molecule-targeted anticancer systems, intracellular protein targets are very difficult to be accessed by antibodies, and also most efforts are made to inhibit protein activity temporarily rather than inactivate them permanently. In this work we firstly designed and synthesized multifunctional polymer-drug conjugates (polythiophene-tamoxifen) for intracellular molecule-targeted binding and inactivation of protein (estrogen receptor α, ERα) for growth inhibition of MCF-7 cancer cells. Small molecule drug was conjugated to polymer side chain for intracellular signal protein targeting, and simultaneously the fluorescent characteristic of polymer for tracing the cellular uptake and localization of polythiophene-drug conjugates by cell imaging. Under light irradiation, the conjugated polymer can sensitize oxygen to produce reactive oxygen species (ROS) that specifically inactivate the targeted protein, and thus inhibit the growth of tumor cells. The conjugates showed selective growth inhibition of ERα positive cancer cells, which exhibits low side effect for our intracellular molecule-targeted therapy system.
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Antineoplásicos Hormonais/química , Portadores de Fármacos/química , Receptor alfa de Estrogênio/antagonistas & inibidores , Polímeros/química , Tamoxifeno/química , Tiofenos/química , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Luz , Células MCF-7 , Microscopia de Fluorescência , Fotoquimioterapia , Espécies Reativas de Oxigênio/metabolismo , Tamoxifeno/administração & dosagem , Tamoxifeno/farmacologiaRESUMO
Except for chemotherapy, surgery, and radiotherapy, photodynamic therapy (PDT) as new therapy modality is already in wide clinic use for the treatment of various diseases. The major bottleneck of this technique is the requirement of outer light source, which always limits effective application of PDT to the lesions in deeper tissue. Here, we first report a new modality for treating cancer and microbial infections, which is activated by chemical molecules instead of outer light irradiation. In this system, in situ bioluminescence of luminol can be absorbed by a cationic oligo(p-phenylene vinylene) (OPV) that acts as the photosensitizer through bioluminescence resonance energy transfer (BRET) process. The excited OPV sensitizes oxygen molecule in the surroundings to produce reactive oxygen species (ROS) that kill the adjacent cancer cells in vitro and in vivo, and pathogenic microbes. By avoiding the use of light irradiation, this work opens a new therapy modality to tumor and pathogen infections.