RESUMO
Because of the particular environment of the tumor microenvironment, improving the deep penetration of drugs in tumor sites is a critical problem to improve the therapeutic effect of the tumor. The ultra-small nanoparticles can achieve deep tumor tissue penetration without modification, which shows tremendous significance in tumor therapy. In this work, the ultra-small permeable carbon dots (PCD) have been developed with near-infrared-II (NIR-II) window photothermal irradiation and good biocompatibility. These PCD showed multi-color fluorescence under visible light and photoacoustic signals under an excitation of 808 nm, guiding fluorescence and photoacoustic imaging for location and distribution in vitro and vivo. The PCD could penetrate the deep tissue in tumor spheroids and tissues. Meanwhile, the irradiated depth of the NIR-II window can provide sufficient photothermal energy with the deep penetration of PCD in tumor tissue to cause tumor ablation. Therefore, this PCD can be used as a safe, fluorescent, and photoacoustic imaging agent for guided NIR-II photothermal tumor therapy, which provides a new direction for the use of ultra-small carbon dots in anticancer therapy in the future.
Assuntos
Nanopartículas , Neoplasias , Carbono , Linhagem Celular Tumoral , Humanos , Raios Infravermelhos , Nanopartículas/efeitos da radiação , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fototerapia/métodos , Terapia Fototérmica , Microambiente TumoralRESUMO
BACKGROUND: Currently, there are no curative drugs for hepatitis B virus (HBV). Complete elimination of HBV covalently closed circular DNA (cccDNA) is key to the complete cure of hepatitis B virus infection. The CRISPR/Cas9 system can directly destroy HBV cccDNA. However, a CRISPR/Cas9 delivery system with low immunogenicity and high efficiency has not yet been established. Moreover, effective implementation of precise remote spatiotemporal operations in CRISPR/Cas9 is a major limitation. RESULTS: In this work, we designed NIR-responsive biomimetic nanoparticles (UCNPs-Cas9@CM), which could effectively deliver Cas9 RNP to achieve effective genome editing for HBV therapy. HBsAg, HBeAg, HBV pgRNA and HBV DNA along with cccDNA in HBV-infected cells were found to be inhibited. These findings were confirmed in HBV-Tg mice, which did not exhibit significant cytotoxicity and minimal off-target DNA damage. CONCLUSIONS: The UCNPs-based biomimetic nanoplatforms achieved the inhibition of HBV replication via CRISPR therapy and it is a potential system for efficient treatment of human HBV diseases.
Assuntos
Materiais Biomiméticos , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Hepatite B/terapia , Nanopartículas , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/efeitos da radiação , Técnicas de Transferência de Genes , Vírus da Hepatite B , Raios Infravermelhos , Camundongos , Camundongos Transgênicos , Nanopartículas/química , Nanopartículas/efeitos da radiaçãoRESUMO
Poor tumor selectivity, low stability and quenched fluorescence are the main challenges to be overcome for nanomedicine, and are mainly caused by the dissociation of the nanostructure and aggregation of chromophores in the biological environment. Herein, covalently connected nanoparticles RGD-graphene-phthalocyanine (RGD-GO-SiPc) were constructed based on RGD peptide, silicon phthalocyanine (SiPc) and graphene oxide (GO) via a conjugation reaction for fluorescence imaging-guided cancer-targeted combinatorial phototherapy. The prepared RGD-GO-SiPc exhibited supreme biological stability, high-contrast fluorescence imaging, significantly enhanced NIR absorption, high photothermal conversion efficiency (25.6%), greatly improved cancer-targeting capability, and synergistic photodynamic (PDT) and photothermal therapy (PTT) efficacy along with low toxicity. Both in vitro and in vivo biological studies showed that RGD-GO-SiPc is a kind of promising multifunctional nanomedicine for fluorescence imaging-guided combined photothermal and photodynamic therapy with dual active/passive tumor-targeting properties.
Assuntos
Antineoplásicos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Nanocompostos/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Feminino , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Grafite/química , Grafite/efeitos da radiação , Grafite/uso terapêutico , Células HEK293 , Humanos , Isoindóis/química , Isoindóis/efeitos da radiação , Isoindóis/uso terapêutico , Luz , Camundongos , Nanocompostos/química , Nanocompostos/efeitos da radiação , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Oligopeptídeos/química , Imagem Óptica , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Oxigênio Singlete/metabolismoRESUMO
We investigated a series of Mn2+-Prussian blue (PB) nanoparticles NazMnxFe1-x[Fe(CN)6]1-yâ¡y·nH2O of similar size, surface state and cubic morphology with various amounts of Mn2+ synthesized through a one step self-assembly reaction. We demonstrated by a combined experimental-theoretical approach that during the synthesis, Mn2+ substituted Fe3+ up to a Mn/Na-Mn-Fe ratio of 32 at% in the PB structure, while for higher amounts, the Mn2[Fe(CN)6] analogue is obtained. For comparison, the post-synthetic insertion of Mn2+ in PB nanoparticles was also investigated and completed with Monte-Carlo simulations to probe the plausible adsorption sites. The photothermal conversion efficiency (η) of selected samples was determined and showed a clear dependence on the Mn2+amount with a maximum efficiency for a Mn/Na-Mn-Fe ratio of 10 at% associated with a dependence on the nanoparticle concentration. Evaluation of the in vitro photothermal properties of these nanoparticles performed on triple negative human breast adenocarcinoma (MDA-MB-231) cells by using continuous and pulsed laser irradiation confirm their excellent PTT efficiency permitting low dose use.
Assuntos
Antineoplásicos/uso terapêutico , Ferrocianetos/uso terapêutico , Manganês/química , Nanopartículas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Ferrocianetos/química , Ferrocianetos/efeitos da radiação , Humanos , Ferro/química , Ferro/efeitos da radiação , Manganês/efeitos da radiação , Nanopartículas/química , Nanopartículas/efeitos da radiação , Processos Fotoquímicos , Terapia Fototérmica , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-ZebraRESUMO
We report photoluminescence and photoionization properties of Sm2+ ions generated by X-irradiation of nanocrystalline CaF2:Sm3+ prepared by coprecipitation. The nanocrystals were of 46 nm average crystallite size with a distribution of ±20 nm and they were characterised by XRD, TEM and SEM-EDS. At room temperature, the X-irradiated sample displayed broad electric dipole allowed Sm2+ 4f55d (A1u) â 4f6 7F1 (T1g) luminescence at 725 nm that narrowed to an intense peak at 708 nm on cooling to â¼30 K. The narrow f-f transitions of Sm3+ were also observed. The X-irradiation-induced reduction of Sm3+ + e- â Sm2+ as a function of X-ray dose was investigated over a very wide dynamic range from 0.01 mGy to 850 Gy by monitoring the photoluminescence intensities of both Sm2+ and Sm3+ ions. The reverse Sm2+ â Sm3+ + e- photoionization can be modelled by employing dispersive first-order kinetics and using a standard gamma distribution function, yielding an average separation of 13 Å between the Sm2+ ions and the hole traps (e.g. oxide ion impurities). The present results point towards potential applications of Sm doped CaF2 nanocrystals in the fields of dosimetry and X-ray imaging.
Assuntos
Fluoreto de Cálcio/efeitos da radiação , Nanopartículas/efeitos da radiação , Samário/efeitos da radiação , Raios X , Fluoreto de Cálcio/química , Luminescência , Nanopartículas/química , Samário/químicaRESUMO
Surgical site infections constitute a major health concern that may be addressed by conferring antibacterial properties to surgical tools and medical devices via functional coatings. Bio-sourced polymers are particularly well-suited to prepare such coatings as they are usually safe and can exhibit intrinsic antibacterial properties or serve as hosts for bactericidal agents. The goal of this Review is to highlight the unique contribution of photochemistry as a green and mild methodology for the development of such bio-based antibacterial materials. Photo-generation and photo-activation of bactericidal materials are illustrated. Recent efforts and current challenges to optimize the sustainability of the process, improve the safety of the materials and extend these strategies to 3D biomaterials are also emphasized.
Assuntos
Antibacterianos/farmacologia , Fotoquímica/métodos , Polímeros/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/efeitos da radiação , Bactérias/efeitos dos fármacos , Produtos Biológicos/química , Produtos Biológicos/efeitos da radiação , Química Verde , Humanos , Luz , Nanopartículas/química , Nanopartículas/efeitos da radiação , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Polimerização/efeitos da radiação , Polímeros/síntese química , Polímeros/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet-triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states. RESULTS: Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo. CONCLUSIONS: This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis.
Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas , Fotólise , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Luz , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/efeitos da radiação , Paclitaxel/química , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , FótonsRESUMO
Multimodal synergistic therapy has gained increasing attention in cancer treatment to overcome the limitations of monotherapy and achieve high anticancer efficacy. In this study, a synergistic phototherapy and hypoxia-activated chemotherapy nanoplatform based on natural melanin nanoparticles (MPs) loaded with the bioreduction prodrug tirapazamine (TPZ) and decorated with hyaluronic acid (HA) was developed. A self-reporting aggregation-induced emission (AIE)-active photosensitizer (PS) (BATTMN) was linked to the prepared nanoparticles by boronate ester bonds. The MPs and BATTMN-HA played roles as quenchers for PS and cancer targeting/photodynamic moieties, respectively. As a pH sensitive bond, the borate ester bonds between HA and BATTMN are hydrolysed in the acidic cancer environment, thereby separating BATTMN from the nanoparticles and leading to the induction of fluorescence for imaging-guided synergistic phototherapy/hypoxia-activated chemotherapy under dual irradiation. TPZ can be released upon activation by pH, near-infrared (NIR) and hyaluronidase (Hyal). Particularly, the hypoxia-dependent cytotoxicity of TPZ was amplified by oxygen consumption in the tumor intracellular environment induced by the AIE-active PS in photodynamic therapy (PDT). The nanoparticles developed in our research showed favorable photothermal conversion efficiency (η = 37%), desired cytocompatibility, and excellent synergistic therapeutic efficacy. The proposed nanoplatform not only extends the application scope of melanin materials with AIE-active PSs, but also offers useful insights into developing multistimulus as well as multimodal synergistic tumor treatment.
Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Melaninas/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/química , Ácidos Borônicos/química , Ácidos Borônicos/efeitos da radiação , Ácidos Borônicos/uso terapêutico , Terapia Combinada , Tratamento Farmacológico , Feminino , Humanos , Células MCF-7 , Melaninas/química , Melaninas/efeitos da radiação , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Pró-Fármacos/química , Pró-Fármacos/uso terapêutico , Tirapazamina/química , Tirapazamina/uso terapêutico , Hipóxia Tumoral/fisiologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In this study, we introduced four "claw-like" units of dipicolylamine (DPA) to a tetraphenylethylene (TPE)-based organic molecular cage (DPA-TPE-Cage). Coordinated with Zn2+ ions, the obtained ZnDPA-TPE-Cage exhibited aggregation induced emission (AIE) effects and oxidase-like properties, which endowed it with the ability to selectively image and kill Gram-positive bacteria S. aureus efficiently.
Assuntos
Antibacterianos/farmacologia , Corantes Fluorescentes/farmacologia , Nanopartículas/química , Aminas/química , Aminas/farmacologia , Aminas/efeitos da radiação , Antibacterianos/química , Antibacterianos/efeitos da radiação , Catálise/efeitos da radiação , Membrana Celular/efeitos dos fármacos , Corantes Fluorescentes/química , Corantes Fluorescentes/efeitos da radiação , Luz , Testes de Sensibilidade Microbiana , Nanopartículas/efeitos da radiação , Ácidos Picolínicos/química , Ácidos Picolínicos/farmacologia , Ácidos Picolínicos/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Estilbenos/química , Estilbenos/farmacologia , Estilbenos/efeitos da radiação , Zinco/química , Zinco/farmacologia , Zinco/efeitos da radiaçãoRESUMO
Rational manipulation of nonradiative decay channels is of crucial significance to improve photothermal conversion efficiency (PCE) and design photothermal agents. We first used the "internal and external combined" nonradiative decay strategy to enhance PCE. Specifically, organic IR-Y6 NPs with strong NIR absorption and high molar extinction coefficient were prepared and characterized. By means of TD-DFT calculations and fs-TA spectroscopy, the dual nonradiative decay channels composed of the free rotor (external strategy) and ultrafast dark excited states (DESs) between S0 and S1 states (internal strategy) were proved, which significantly enhanced PCE, up to 66%. IR-Y6 NPs were applied to a mice tumor model for photoacoustic image-guided photothermal therapy, showing complete tumor ablation ability and good biocompatibility for the normal organs. This work is of significance to deeply understand the nonradiation decay mechanism and rational design of high-performance PTT agents.
Assuntos
Antineoplásicos/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Indanos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Terapia Combinada , Teoria da Densidade Funcional , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/síntese química , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos da radiação , Humanos , Indanos/síntese química , Indanos/efeitos da radiação , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Modelos Químicos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Técnicas Fotoacústicas , Terapia Fototérmica , Nanomedicina Teranóstica/métodosRESUMO
Using multi-color visible lights for independent optogenetic manipulation of multiple neuronal populations offers the ability for sophisticated brain functions and behavior dissection. To mitigate invasive fiber insertion, infrared light excitable upconversion nanoparticles (UCNPs) with deep tissue penetration have been implemented in optogenetics. However, due to the chromatic crosstalk induced by the multiple emission peaks, conventional UCNPs or their mixture cannot independently activate multiple targeted neuronal populations. Here, we report NIR multi-color optogenetics by the well-designed trichromatic UCNPs with excitation-specific luminescence. The blue, green and red color emissions can be separately tuned by switching excitation wavelength to match respective spectral profiles of optogenetic proteins ChR2, C1V1 and ChrimsonR, which enables selective activation of three distinct neuronal populations. Such stimulation with tunable intensity can not only activate distinct neuronal populations selectively, but also achieve transcranial selective modulation of the motion behavior of awake-mice, which opens up a possibility of multi-color upconversion optogenetics.
Assuntos
Encéfalo/fisiologia , Estimulação Encefálica Profunda/métodos , Raios Infravermelhos , Nanopartículas/efeitos da radiação , Optogenética/métodos , Animais , Encéfalo/citologia , Encéfalo/efeitos da radiação , Cor , Masculino , Camundongos , Microscopia Eletrônica de Transmissão , Modelos Animais , Movimento/fisiologia , Neurônios/fisiologia , Neurônios/efeitos da radiação , Técnicas de Patch-Clamp , Imagem Individual de Molécula/métodos , Técnicas EstereotáxicasRESUMO
Cell nucleus-based photodynamic therapy is a highly effective method for cancer therapy, but it is still challenging to design nucleus-targeting photosensitizers. Here, we propose the "one treatment, multiple irradiations" strategy to achieve nucleus-based photodynamic therapy using the photosensitizer rose bengal (RB)-loaded and mesoporous silica-coated upconversion nanoparticles with the surface modification of amine group (UCNP/RB@mSiO2-NH2 NPs). After implementation into cancer cells, the rationally designed UCNP/RB@mSiO2-NH2 NPs could be specifically accumulated in the acidic lysosomes due to their amino group-decorated surface. Upon a short-term (3 min) irradiation of 980 nm near-infrared light, the reactive oxygen species produced by RB through the Förster resonance energy transfer between the upconversion nanoparticles and RB molecules could effectively destroy lysosomes, followed by the release of the UCNP/RB@mSiO2-NH2 NPs from the lysosomes. Subsequently, these released UCNP/RB@mSiO2-NH2 NPs could be transferred into the cell nucleus, where a second 980 nm light irradiation was conducted to achieve the nucleus-based photodynamic therapy. The rationally designed UCNP/RB@mSiO2-NH2 NPs showed excellent anticancer performance in both two-dimensional and three-dimensional cell models using the "one treatment, multiple irradiations" strategy.
Assuntos
Antineoplásicos/administração & dosagem , Metais Terras Raras/administração & dosagem , Nanopartículas/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Rosa Bengala/administração & dosagem , Dióxido de Silício/administração & dosagem , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Núcleo Celular/química , Núcleo Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Humanos , Luz , Lisossomos/química , Células MCF-7 , Metais Terras Raras/química , Metais Terras Raras/efeitos da radiação , Nanopartículas/química , Nanopartículas/efeitos da radiação , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Espécies Reativas de Oxigênio/química , Rosa Bengala/química , Rosa Bengala/efeitos da radiação , Dióxido de Silício/química , Dióxido de Silício/efeitos da radiação , Esferoides Celulares/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
The development of modern agriculture has prompted the greater input of herbicides, insecticides, and fertilizers. However, precision release and targeted delivery of these agrochemicals still remain a challenge. Here, a pesticide-fertilizer all-in-one combination (PFAC) strategy and deep learning are employed to form a system for controlled and targeted delivery of agrochemicals. This system mainly consists of three components: (1) hollow mesoporous silica (HMS), to encapsulate herbicides and phase-change material; (2) polydopamine (PDA) coating, to provide a photothermal effect; and (3) a zeolitic imidazolate framework (ZIF8), to provide micronutrient Zn2+ and encapsulate insecticides. Results show that the PFAC at concentration of 5 mg mL-1 reaches the phase transition temperature of 1-tetradecanol (37.5 °C) after 5 min of near-infrared (NIR) irradiation (800 nm, 0.5 W cm-2). The data of corn and weed are collected and relayed to deep learning algorithms for model building to realize object detection and further targeted weeding. In-field treatment results indicated that the growth of chicory herb was significantly inhibited when treated with the PFAC compared with the blank group after 24 h under NIR irradiation for 2 h. This system combines agrochemical innovation and artificial intelligence technology, achieves synergistic effects of weeding and insecticide and nutrient supply, and will potentially achieve precision and sustainable agriculture.
Assuntos
Portadores de Fármacos/química , Fertilizantes , Herbicidas/química , Inseticidas/química , Nanopartículas/química , Ácido 2,4-Diclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/toxicidade , Animais , Cichorium intybus/efeitos dos fármacos , Aprendizado Profundo , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Álcoois Graxos/química , Álcoois Graxos/efeitos da radiação , Guanidinas/química , Guanidinas/toxicidade , Herbicidas/toxicidade , Indóis/química , Indóis/efeitos da radiação , Raios Infravermelhos , Insetos/efeitos dos fármacos , Inseticidas/toxicidade , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/efeitos da radiação , Nanopartículas/efeitos da radiação , Neonicotinoides/química , Neonicotinoides/toxicidade , Nitrocompostos/química , Nitrocompostos/toxicidade , Polímeros/química , Polímeros/efeitos da radiaçãoRESUMO
Porphyrin-based nanozymes (Porzymes) have shown promising application potential to fight against tumors using catalytically generated reactive oxygen species from the excessively produced H2O2 in the tumor microenvironment. However, the low coordination porphyrin (CP) loading ratio, difficult controllable nanostructure, low bioavailability, and low biocatalytic activities of current established Porzymes have severely limited their antitumor applications. Here, a novel malignant melanoma cell membrane-coated Pd-based CP nanoplatform (Trojan Porzymes) has been synthesized for biocatalytic and homologous tumor therapies. The Trojan Porzymes exhibit a high CP loading ratio, uniform nanoscale size, single-atom nanostructure, homologous targeted ability, and high-efficiency photo/sono-augmented biocatalytic activities. The enzyme-like biocatalytic experiments display that the Trojan Porzymes can generate abundant â¢OH via chemodynamic path and 1O2 via visible light or ultrasound excitation. Then we demonstrate that the Trojan Porzymes show homologous targeting ability to tumor cells and can achieve efficient accumulation and long-term retention in cancer tissues. Our in vivo data further disclose that the photo/sono-assisted chemodynamic therapies can significantly augment the treatment efficiency of malignant melanoma. We believe that our work will afford a new biocatalytic and homologous strategy for future clinical malignant melanoma treatments, which may inspire and guide more future studies to develop individualized biomedicine in precise tumor therapies.
Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Porfirinas/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Catálise , Membrana Celular/química , Complexos de Coordenação/química , Complexos de Coordenação/efeitos da radiação , Complexos de Coordenação/uso terapêutico , Células Endoteliais da Veia Umbilical Humana , Humanos , Radical Hidroxila/metabolismo , Luz , Camundongos , Nanopartículas/química , Nanopartículas/efeitos da radiação , Porfirinas/química , Porfirinas/efeitos da radiação , Radiossensibilizantes/química , Radiossensibilizantes/efeitos da radiação , Ondas UltrassônicasRESUMO
Despite its success against cancer, photothermal therapy (PTT) (>50 °C) suffers from several limitations such as triggering inflammation and facilitating immune escape and metastasis and also damage to the surrounding normal cells. Mild-temperature PTT has been proposed to override these shortcomings. We developed a nanosystem using HepG2 cancer cell membrane-cloaked zinc glutamate-modified Prussian blue nanoparticles with triphenylphosphine-conjugated lonidamine (HmPGTL NPs). This innovative approach achieved an efficient mild-temperature PTT effect by downregulating the production of intracellular ATP. This disrupts a section of heat shock proteins that cushion cancer cells against heat. The physicochemical properties, anti-tumor efficacy, and mechanisms of HmPGTL NPs both in vitro and in vivo were investigated. Moreover, the nanoparticles cloaked with the HepG2 cell membrane substantially prolonged the circulation time in vivo. Overall, the designed nanocomposites enhance the efficacy of mild-temperature PTT by disrupting the production of ATP in cancer cells. Thus, we anticipate that the mild-temperature PTT nanosystem will certainly present its enormous potential in various biomedical applications.
Assuntos
Antineoplásicos/uso terapêutico , Membrana Celular/química , Ferrocianetos/química , Mitocôndrias/efeitos dos fármacos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/efeitos da radiação , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Ferrocianetos/efeitos da radiação , Ferrocianetos/toxicidade , Células Hep G2 , Humanos , Indazóis/química , Indazóis/uso terapêutico , Raios Infravermelhos , Camundongos Nus , Nanocompostos/química , Nanocompostos/toxicidade , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Terapia FototérmicaRESUMO
Nanoscale hydroxyapatite (nHA) is considered as a promising drug carrier or therapeutic agent against malignant tumors. But the strong agglomeration tendency and lack of active groups seriously hamper their usage in vivo. To address these issues, we fabricated an organic-inorganic hybrid nanosystem composed of poly(acrylic acid) (PAA), nHA, and indocyanine green (ICG), and further modified with glucose to give a targeting nanosystem (GA@HAP/ICG-NPs). These hybrid nanoparticles (â¼90 nm) showed excellent storage and physiological stability assisted by PAA and had a sustained drug release in an acidic tumor environment. In vitro cell experiments confirmed that glucose-attached particles significantly promoted cellular uptake and increased intracellular ICG and Ca2+ concentrations by glucose transporter 1 (GLUT1)-mediated endocytosis. Subsequently, the excessive Ca2+ induced cell or organelle damage and ICG triggered photothermal and photodynamic effects (PTT/PDT) under laser irradiation, resulting in enhanced cell toxicity and apoptosis. In vivo tests revealed that the hybrid nanosystem possessed good hemocompatibility and biosafety, facilitating in vivo circulation and usage. NIR imaging further showed that tumor tissues had more drug accumulation, resulting in the highest tumor growth inhibition (87.89%). Overall, the glucose-targeted hybrid nanosystem was an effective platform for collaborative therapy and expected to be further used in clinical trials.
Assuntos
Antineoplásicos/uso terapêutico , Durapatita/uso terapêutico , Verde de Indocianina/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Resinas Acrílicas/química , Resinas Acrílicas/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Portadores de Fármacos/toxicidade , Durapatita/química , Durapatita/toxicidade , Glucose/química , Glucose/toxicidade , Células Hep G2 , Humanos , Verde de Indocianina/química , Verde de Indocianina/efeitos da radiação , Verde de Indocianina/toxicidade , Raios Infravermelhos , Masculino , Camundongos Endogâmicos ICR , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Terapia FototérmicaRESUMO
To promote bactericidal activity, improve photostability and safety, novel antibacterial nanoparticle system based on photodynamic action (PDA) was prepared here through conjugation of photosensitizer hematoporphyrin (HP) onto carboxymethyl chitosan (CMCS) via amide linkage and followed by ultrasonic treatment. The system was stable in PBS (pH 7.4) and could effectively inhibit the photodegradation of conjugated HP because of aggregation-caused quenching effect. ROS produced by the conjugated HP under light exposure could change the structure of nanoparticles by oxidizing the CMCS skeleton and thereby significantly promote the photodynamic activity of HP and its photodynamic activity after 6 h was higher than that of HP·2HCl under the same conditions. Antibacterial experiments showed that CMCS-HP nanoparticles had excellent photodynamic antibacterial activity, and the bacterial inhibition rates after 60 min of light exposure were greater than 97%. Safety evaluation exhibited that the nanoparticles were safe to mammalian cells, showing great potential for antibacterial therapy.
Assuntos
Antibacterianos/farmacologia , Quitosana/análogos & derivados , Hematoporfirinas/farmacologia , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Quitosana/síntese química , Quitosana/farmacologia , Quitosana/efeitos da radiação , Quitosana/toxicidade , Escherichia coli/efeitos dos fármacos , Hematoporfirinas/síntese química , Hematoporfirinas/efeitos da radiação , Hematoporfirinas/toxicidade , Luz , Camundongos , Testes de Sensibilidade Microbiana , Células NIH 3T3 , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus , Tensoativos/síntese química , Tensoativos/farmacologia , Tensoativos/efeitos da radiação , Tensoativos/toxicidadeRESUMO
The implementation of light-sensitive Pickering emulsions with spatio-temporal responsiveness in advanced applications like drug-delivery, colloidal or reaction engineering would open new avenues. However, curiously, light-sensitive Pickering emulsions are barely studied in the literature and their biocompatibility and/or degradability scarcely addressed. Thus, their development remains a major challenge. As an original strategy, we synthesized light-sensitive nanoparticles based on biocompatible Poly(NitroBenzylAcrylate) grafted dextran (Dex-g-PNBA) to stabilize O/W Pickering emulsions. The produced emulsions were stable in time and could undergo time and space-controlled destabilization under light stimulus. Irradiation time and alkaline pH-control of the aqueous phase were proved to be the actual key drivers of destabilization. As the nanoparticles themselves were photolyzed under light stimulus, possible harmful effects linked to accumulation of nanomaterials should be avoided. In addition to UV light (365 nm), visible light (405 nm) was successfully used for the spatio-temporal destabilization of the emulsions, offering perspectives for life science applications.
Assuntos
Dextranos/química , Emulsões/química , Nanopartículas/química , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Resinas Acrílicas/efeitos da radiação , Alcanos/química , Dextranos/síntese química , Dextranos/efeitos da radiação , Emulsões/síntese química , Luz , Nanopartículas/efeitos da radiação , Fotólise , Estudo de Prova de Conceito , Água/químicaRESUMO
The lack of cancer cell specificity and the occurrence of multidrug resistance (MDR) are two major obstacles in the treatment of hepatocellular carcinoma (HCC). To tackle these challenges, a novel nanoparticle (NP)-based drug delivery system (DDS) with a core/shell structure consisted of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-galactose (Gal)/polydopamine (PDA) is fabricated. The NP is loaded with doxorubicin (DOX) and a nitric oxide (NO) donor N,N'-di-sec-butyl-N,N'-dinitroso-1,4-phenylenediamine (BNN) sensitive to heat to afford NO-DOX@PDA-TPGS-Gal. The unique binding of Gal to asialoglycoprotein receptor (ASGPR) and the pH-sensitive degradation of NP ensure the targeted transportation of NP into liver cells and the release of DOX in HCC cells. The near-infrared (NIR) light further facilitates DOX release and initiates NO generation from BNN due to the photothermal property of PDA. In addition to the cytotoxicity contributed by DOX, NO, and heat, TPGS and NO act as MDR reversal agents to inhibit P-glycoprotein (P-gp)-related efflux of DOX by HepG2/ADR cells. The combined chemo-photothermal therapy (chemo-PTT) by NO-DOX@PDA-TPGS-Gal thus shows potent anti-cancer activity against drug-resistant HCC cells in vitro and in vivo and significantly prolongs the life span of drug-resistant tumor-bearing mice. The present work provides a useful strategy for highly targeted and MDR reversal treatment of HCC.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Neoplasias Hepáticas/tratamento farmacológico , Doadores de Óxido Nítrico/uso terapêutico , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Tratamento Farmacológico , Galactose/química , Humanos , Indóis/química , Indóis/efeitos da radiação , Raios Infravermelhos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/efeitos da radiação , Doadores de Óxido Nítrico/química , Compostos Nitrosos/química , Compostos Nitrosos/uso terapêutico , Terapia Fototérmica , Polímeros/química , Polímeros/efeitos da radiação , Ratos Sprague-Dawley , Vitamina E/química , Vitamina E/efeitos da radiação , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
There is a need for safe and sustainable alternatives in the coating industry. Bio-based coatings are interesting in this perspective. Although various oils and waxes have been used as traditional wood coatings, they often lack sufficient durability. Lignin is an abundant natural polyphenol that can be used to cure epoxies, but its poor water solubility has impeded the use of unmodified lignin in coatings in the past. To address this issue, water-dispersible colloidal lignin particles (CLPs) and an epoxy compound, glycerol diglycidyl ether (GDE), were used to prepare multiprotective bio-based surface coatings. With the GDE/CLP ratios of 0.65 and 0.52 g/g, the cured CLP-GDE films became highly resistant to abrasion and heat. When applied as a coating on wooden substrates, the particulate morphology enabled effective protection against water, stains, and sunlight with very thin layers (less than half the weight of commercial coatings) while retaining the wood's breathability excellently. Optimal hydrophobicity was reached with a coat weight of 6.9 g(CLP)/m2, resulting in water contact angle values of up to 120°. Due to their spherical shape and chemical structure, the CLPs acted as both a hardener and a particulate component in the coating, which removed the need for an underlying binding polymer matrix. Light interferometry measurements showed that while commercial polymeric film-forming coatings smoothened the substrate noticeably, the particulate morphology retained the substrate's roughness in lightweight coatings, allowing for a high water contact angle. This work presents new strategies for lignin applications in durable particulate coatings and their advantages compared to both currently used synthetic and bio-based coatings.