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1.
J Control Release ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32061620

RESUMO

Carrier-free nanodrug via small-molecule assembly is a promising alternative strategy for tumor therapy. Thus, developing a self-recognizing carrier-free nanodrug without introduction of foreign ligand is very attractive to meet both targeting and therapeutic requirements while reducing structural complexity. Here we fabricated a tumor microenvironment-activated self-targeting nanodrug, via co-assembly of hydroxycamptothecin (HCPT) and bi-functional methotrexate (MTX, not only has antitumor effect but also shows innate affinity towards folate receptors) followed by surface covering through acidity-responsive polyethylene glycol (PEG). Notably, the morphology and size of MTX-HCPT nanodrug could be tuned by varying the drug-to-drug ratio and assembly time. The PEG shell of our nanodrug could be detached in response to acidic tumor microenvironment, and then MTX could be exposed for self-targeting to enhance tumor cell uptake. Subsequently, the shell-detached nanodrug could be dissociated in relatively stronger acidic lysosomal environment, resulting in burst release of both drugs. Further in vitro and in vivo studies demonstrated that our nanodrug showed a ~2.98-fold increase in cancer cell uptake, a ~1.25-fold increase in drug accumulation at tumor site, a significantly lower CI50 value of ~0.3, a ~27.3% improvement in tumor inhibition comparing with the corresponding non-responsive nanodrug. Taken together, the here reported tumor microenvironment-activated self-recognizing nanodrug might be an extremely promising strategy for synergistically enhancing chemotherapy efficiency with minimized side effects.

2.
Nat Commun ; 11(1): 573, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996677

RESUMO

Hypoxia in solid tumors is thought to be an important factor in resistance to therapy, but the extreme microscopic heterogeneity of the partial pressures of oxygen (pO2) between the capillaries makes it difficult to characterize the scope of this phenomenon without invasive sampling of oxygen distributions throughout the tissue. Here we develop a non-invasive method to track spatial oxygen distributions in tumors during fractionated radiotherapy, using oxygen-dependent quenching of phosphorescence, oxygen probe Oxyphor PtG4 and the radiotherapy-induced Cherenkov light to excite and image the phosphorescence lifetimes within the tissue. Mice bearing MDA-MB-231 breast cancer and FaDu head neck cancer xenografts show different pO2 responses during each of the 5 fractions (5 Gy per fraction), delivered from a clinical linear accelerator. This study demonstrates subsurface in vivo mapping of tumor pO2 distributions with submillimeter spatial resolution, thus providing a methodology to track response of tumors to fractionated radiotherapy.

3.
Cytometry A ; 97(1): 31-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31403260

RESUMO

Pathological diagnosis plays an important role in the diagnosis and treatment of hepatocellular carcinoma (HCC). The traditional method of pathological diagnosis of most cancers requires freezing, slicing, hematoxylin and eosin staining, and manual analysis, limiting the speed of the diagnosis process. In this study, we designed a one-dimensional convolutional neural network to classify the hyperspectral data of HCC sample slices acquired by our hyperspectral imaging system. A weighted loss function was employed to promote the performance of the model. The proposed method allows us to accelerate the diagnosis process of identifying tumor tissues. Our deep learning model achieved good performance on our data set with sensitivity, specificity, and area under receiver operating characteristic curve of 0.871, 0.888, and 0.950, respectively. Meanwhile, our deep learning model outperformed the other machine learning methods assessed on our data set. The proposed method is a potential tool for the label-free and real-time pathologic diagnosis. © 2019 International Society for Advancement of Cytometry.

4.
Adv Healthc Mater ; 9(1): e1900996, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746153

RESUMO

Photodynamic therapy (PDT) usually aggravates tumor hypoxia, which promotes the survival and metastasis of residue cancer cells; furthermore, although PDT-induced immunogenic death of cancer cells can induce host antitumor responses, such responses are generally weak and not enough to eliminate the residue cancer cells. Here, metal-organic framework (MOF)-based nanoparticles to combine PDT, antihypoxic signaling, and CpG adjuvant as an in situ tumor vaccine to boost host anticancer responses after PDT are designed. The MOF-based nanoparticles are self-assembled from H2 TCPP and zirconium ions with hypoxia inducible factor (HIF) signaling inhibitor (ACF) and immunologic adjuvant (CpG) loading, and hyaluronic acid (HA) coating on the surface. The final nanoparticles (PCN-ACF-CpG@HA) can specifically target cancer cells overexpressing CD44 receptor though HA; the aggravated hypoxic survival signaling after PDT can be blocked by ACF to inhibit the HIF-1α induced survival and metastasis. With the help of CpG adjuvant, the tumor associated antigens generated from PDT-based cancer cell destruction can initiate strong antitumor immune responses to eliminate residue cancer cells. Taken together, a novel in situ immunostimulatory strategy is designed to synergistically enhance therapeutic effects of PDT by activating host antitumor immune-responses both in vitro and in vivo, which may have great potential for clinical translation in future.

5.
Am J Cancer Res ; 9(10): 2064-2078, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31720075

RESUMO

The activating receptor natural killer group 2, member D (NKG2D) is involved in both innate and adaptive immunities, and functions as a "master switch" in determining the activation status of natural killer (NK) cells. NKG2D binds to a diverse family of ligand molecules, which are only expressed at low levels in normal cells but can be upregulated by a cellular stress response. The NKG2D-NKG2D ligand (NKG2DL) pathway has been considered to be promising target for immunotherapy because of the selective expression of "stress-induced ligands" on tumor cells and the strong NK cell activating potency of NKG2D. Diverse strategies that are aimed at targeting the NKG2D pathway for cancer therapy are based on a thorough understanding of this mechanism, as well as that of NKG2D-mediated cancer immunity. In this review, we summarize the major findings regarding the antitumor immune response mediated by the NKG2D receptor and its ligands, and discuss the potential clinical applications of targeting the NKG2D/NKG2DL pathway for immunotherapy in cancer patients.

6.
ACS Appl Mater Interfaces ; 11(45): 41829-41841, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31617343

RESUMO

Photodynamic therapy (PDT) is an encouraging alternative therapy for melanoma treatment and Ce6-mediated PDT has shown some exciting results in clinical trials. However, PDT in melanoma treatment is still hampered by some melanoma's protective mechanisms like antiapoptosis mechanisms and treatment escape pathways. Combined therapy and enhancing immune stimulation were proposed as effective strategies to overcome this resistance. In this paper, a Chlorin-based photoactivable Galectin-3-inhibitor nanoliposome (PGIL) was designed for enhanced Melanoma PDT and immune activation of Natural Killer (NK) cells. PGIL were synthesized by encapsulating the photosensitizer chlorin e6 and low molecular citrus pectin in the nanoliposome to realize NIR-triggered PDT and low molecular citrus pectin (LCP) release into the cytoplasm. The intracellular release of LCP inhibits the activity of galectin-3, which increases the apoptosis, inhibits the invade ability, and enhances the recognition ability of Natural Killer (NK) cells to tumor cells in melanoma cells after PDT. These effects of PGIL were tested in cells and nude mice, and the mechanisms during the in vivo treatment were preliminarily studied. The results showed that PGIL can be an effective prodrug for melanoma therapy.

7.
J Biomed Opt ; 23(12): 1-12, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30552757

RESUMO

Photoacoustic responses induced by laser-excited photothermal bubbles (PTBs) in colloidal gold solutions are relevant to the theranostics quality in biomedical applications. Confined to the complexity of nonstationary, multiscale events, and multiphysical parameters of PTBs, systematic studies of the photoacoustic effects remain obscure. Photoacoustic effects mediated by PTB dynamics and a physical mechanism are studied based on a proof-of-principle multimodal platform integrating side-scattering imaging, time-resolved optical response, and acoustic detection. Results show excitation energy, nanoparticle (NP) size, and NP concentration have strong influence on photoacoustic responses. Under the characteristic enhancement regime, the photoacoustic signal amplitude increases linearly with excitation energy and increases quadratically with the NP diameter. As for the effects of the NP concentration (characterized by absorption coefficient), a higher photoacoustic signal amplitude is generally induced by a dense NP distribution. However, with an increase in the NP size, the shielding effect of NP swarm prevents the increase of photoacoustic responses. This study presents experimental evidence of some key physical phenomena governing the PTB-induced photoacoustic signal generation in gold NP suspensions, which may help enrich theranostic approaches in clinical applications by rationalizing operation parameters.


Assuntos
Nanopartículas/química , Técnicas Fotoacústicas/métodos , Nanomedicina Teranóstica/métodos , Desenho de Equipamento , Coloide de Ouro/química , Modelos Químicos , Técnicas Fotoacústicas/instrumentação , Volatilização
8.
Opt Express ; 26(22): 28560-28575, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30470031

RESUMO

Multiple breakdowns in liquids still remains obscure for its complex, non-equilibrium and transient dynamic process. We introduced three methods, namely, plasma imaging, light-scattering technique, and acoustic detection, to measure the multiple breakdown in water induced by focused nanosecond laser pulses simultaneously. Our results showed that linear dependence existed among the cavitation-bubble lifetime, the far-field peak pressure of the initial shock wave, and the corresponding plasma volume. Such a relationship can be used to evaluate the ideal size and energy of each bubble during multiple breakdown. The major bubble lifetime was hardly affected by the inevitable coalescence of cavitation bubbles, thereby confirming the availability of light-scattering technique on the estimation of bubble size during multiple breakdown. Whereas, the strength of collapse-shock-wave and the subsequent rebound of bubbles was strongly influenced, i.e., the occurrence of multiple breakdown suppressed the cavitation-bubble energy being converted into collapse-shock-wave energy but enhanced conversion into rebound-bubble energy. This study is a valuable contribution to research on the rapid mixing of microfluidics, damage control of microsurgery, and photoacoustic applications.

9.
Analyst ; 144(1): 265-273, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30398232

RESUMO

A conductometric immunoassay protocol was designed for the sensitive detection of a liver cancer biomarker, alpha-fetoprotein (AFP), in biological fluids by using enzyme-conjugated nanometer-sized enzyme-doped silica beads. Initially, urease molecules were doped into nanosilica particles by using the reverse micelle method. Thereafter, arginase-labeled anti-AFP antibodies were covalently conjugated onto the surface of the synthesized nanoparticles. The immunoreaction was carried out in a monoclonal anti-AFP capture antibody-coated microplate with a sandwich-type assay format by using bienzyme-functionalized silica nanobeads as the recognition elements. Upon l-arginine introduction, the substrate was cleaved into urea and l-ornithine on the basis of the arginase enzymatic reaction, and the as-produced urea was then decomposed into ammonia (NH4+) and bicarbonate (HCO3-) ions by the doped urease, thus causing the variation in the local conductivity of the detection solution on an interdigitated conductometric transducer. Under optimal conditions, the developed immunosensing system exhibited good conductometric responses toward target AFP within a dynamic linear range of 0.01-100 ng mL-1 at a relatively low detection limit of 4.8 pg mL-1 based on the 3sB criterion. Importantly, good reproducibility, high specificity and acceptable method accuracy were acquired for the analysis of human serum specimens in liver cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Imunoensaio/métodos , Neoplasias Hepáticas/sangue , Nanoconjugados/química , Dióxido de Silício/química , alfa-Fetoproteínas/análise , Animais , Anticorpos Imobilizados/imunologia , Anticorpos Monoclonais/imunologia , Arginase/química , Arginina/química , Biomarcadores Tumorais/imunologia , Canavalia/enzimologia , Bovinos , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Camundongos , Reprodutibilidade dos Testes , Urease/química , alfa-Fetoproteínas/imunologia
10.
Drug Deliv ; 25(1): 1516-1525, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29968512

RESUMO

Gene delivery as a promising and valid tool has been used for treating many serious diseases that conventional drug therapies cannot cure. Due to the advancement of physical technology and nanotechnology, advanced physical gene delivery methods such as electroporation, magnetoporation, sonoporation and optoporation have been extensively developed and are receiving increasing attention, which have the advantages of briefness and nontoxicity. This review introduces the technique detail of membrane perforation, with a brief discussion for future development, with special emphasis on nanoparticles mediated optoporation that have developed as an new alternative transfection technique in the last two decades. In particular, the advanced physical approaches development and new technology are highlighted, which intends to stimulate rapid advancement of perforation techniques, develop new delivery strategies and accelerate application of these techniques in clinic.


Assuntos
Permeabilidade da Membrana Celular/fisiologia , Membrana Celular/genética , Membrana Celular/metabolismo , Técnicas de Transferência de Genes , Animais , Eletroporação/métodos , Técnicas de Transferência de Genes/tendências , Humanos
11.
J Biomed Nanotechnol ; 14(8): 1430-1447, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29903058

RESUMO

The poor cell membrane penetration ability of photosensitizers resulted in the limited antitumor effect, thereby hampered their potential in clinical translation. The high toxic side effect and multidrug resistance of chemotherapeutic agents during in clinical chemical therapy should be resolved. Nanosystem integrated with photosensitizer and novel targeting chemotherapy agent may be an effective strategy for overcoming clinical or preclinical drawbacks of monotherapy and enhancing therapeutic effect. Therefore, a nanosized micelle F127 integrated with Apogossypolone (ApoG2) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) (referred as F127-ApoG2@AlPcS4) was synthesized to induce the cell death quickly for reducing the risk of resistance and enhancing gastric cancer therapeutic efficiency by combining AlPcS4/photodynamic therapy and ApoG2/chemotherapy. Hydrophobic of ApoG2 and hydrophilic of AlPcS4 self-assembled into this micelle to formation of core-shell structure based on the amphiphilic character of F127 micelle. The reactive oxygen species-dependent mitochondria membrane permeability was improved effectively because of reactive oxygen species generation of ApoG2, thereby resulting in a considerable amount of AlPcS4 and ApoG2 entering the mitochondrial. The AlPcS4 binding site was altered from the cytoplasm to the cell nucleus at higher concentration because of the existence of ApoG2. With irradiation, ApoG2 and AlPcS4 showed effective synergistic anti-tumor effect through inducing apoptosis due to singlet oxygen production regulated mainly by AlPcS4, reactive oxygen species accumulation and calcium overload regulated mainly by ApoG2. Intranuclear AlPcS4 caused cell death through necrosis. The apoptosis induced by AlPcS4 was earlier than ApoG2. In summary, F127-ApoG2@AlPcS4 quickly induced a long-lasting apoptosis that led to cell death, which could be a promising nanosized reagent for gastric cancer therapy based on chemo-photodynamic combined therapy.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Apoptose , Linhagem Celular Tumoral , Humanos , Nanotecnologia , Oxigênio Singlete
12.
Oncol Rep ; 40(1): 165-178, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29767247

RESUMO

Limited cellular delivery and internalization efficiency of Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) induce poor penetration ability in cells and a slight photodynamic therapy (PDT) effect on gastric cancer. The combination treatment of AlPcS4/PDT with low­dose chemotherapeutic agents may provide a promising treatment strategy to increase the weak delivery efficiency of AlPcS4, reducing the dose of chemical agents without reducing efficacy, and improving apoptosis­inducing abilities, thereby increasing the antitumor effects and decreasing the noxious side effects on gastric cancer. We investigated and compared the synergistic antitumor growth effect on gastric cancer cells by combining AlPcS4/PDT treatment with different low­dose chemotherapeutic agents, namely, 5­fluorouracil (5­FU), doxorubicin (DOX), cisplatin (CDDP), mitomycin C (MMC), and vincristine (VCR). The inhibitory effect was increased in treatments that combined AlPcS4/PDT with all the aforementioned low­dose chemotherapeutic agents, to a different extent. An evident synergistic effect was obtained in the combination treatment of AlPcS4/PDT with low­dose 5­FU, DOX, and MMC by increasing AlPcS4 intracellular uptake ability, improving apoptosis­inducing abilities, and prolonging apoptosis­inducing time. The low­dose chemotherapeutic agents prolonged the apoptosis­inducing period of AlPcS4/PDT, and AlPcS4/PDT quickly improved apoptosis­inducing abilities of chemotherapy even at low doses. Generally, the combination treatment of AlPcS4/PDT with low­dose chemotherapeutic agents had significant antitumor growth effects in addition to a low dark­cytotoxicity effect on gastric cancer, thereby representing an effective and feasible therapy method for gastric cancer.


Assuntos
Apoptose/efeitos dos fármacos , Indóis/farmacologia , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Linhagem Celular Tumoral , Cisplatino/farmacologia , Terapia Combinada , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Sinergismo Farmacológico , Fluoruracila/farmacologia , Humanos , Mitomicina/farmacologia , Fotoquimioterapia , Neoplasias Gástricas/patologia , Vincristina/farmacologia
13.
Int J Nanomedicine ; 13: 2143-2160, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29692611

RESUMO

Purpose: Plasmonic nanostructure-mediated photothermal therapy (PTT) is a promising alternative therapy for the treatment of skin cancer and other diseases. However, the insufficient efficiency of PTT at irradiation levels tolerable to tissues and the limited biodegradability of nanomaterials are still crucial challenges. In this study, a novel nanosystem for PTT based on liposome-nanoparticle assemblies (LNAs) was established. Materials and methods: Thermal-sensitive liposomes (TSLs) encapsulating cantharidin (CTD) were coated with gold nanoparticles (GNPs) and used in near-infrared (NIR) illumination-triggered PTT and thermally induced disruption on A431 cells. Results: The coated GNPs disintegrated into small particles of 5-6 nm after disruption of TSLs, allowing their clearance by the liver and kidneys. CTD encapsulated in the TSLs was released into cytoplasm after PTT. The released CTD increased the apoptosis of PTT-treated tumor cells by blocking the heat shock response (HSR) and inhibiting the expression of HSP70 and BAG3 inhibiting the expression of HSP70 and BAG3 with the synergistic enhancement of CTD, the new nanosystem CTD-encapsulated TSLs coated with GNPs (CTD-TSL@GNPs) had an efficient PTT effect using clinically acceptable irradiation power (200 mW//cm2) on A431 cells. Conclusion: The developed CTD-TSL@GNPs may be a promising PTT agent for clinical skin cancer therapy.


Assuntos
Cantaridina/farmacologia , Lipossomos/química , Nanopartículas Metálicas/uso terapêutico , Fototerapia/métodos , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/metabolismo , Cantaridina/administração & dosagem , Cantaridina/química , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Ouro/química , Ouro/farmacologia , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Nanopartículas Metálicas/química
14.
Int J Nanomedicine ; 13: 2017-2036, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29670347

RESUMO

Purpose: As a promising photodynamic therapy (PDT) agent, Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) provides deep penetration into tissue, high quantum yields, good photostability, and low photobleaching. However, its low delivery efficiency and high binding affinity to serum albumin cause its low penetration into cancer cells, further limiting its PDT effect on gastric cancer. In order to improve AlPcS4/PDT effect, the AlPcS4 delivery sys tems with different drug carriers were synthesized and investigated. Materials and methods: Gold nanorods, cationic liposomes, and Pluronic® F127 nanomicellars were used to formulate the AlPcS4 delivery systems. The anticancer effect was evaluated by CCK-8 assay and colony formation assay. The delivery efficiency of AlPcS4 and the binding affinity to serum proteins were determined by fluorescence intensity assay. The apoptosis and necrosis ability, reactive oxygen species and singlet oxygen generation, mitochondrial transmembrane potential and ([Ca2+]i) concentration were further measured to evaluate the mechanism of cell death. Results: The series of synthesized AlPcS4 delivery systems with different drug carriers improve the limited PDT effect in varying degrees. In contrast, AlPcS4 complex with gold nanorods has significant anticancer effects because gold nanorods are not only suitable for AlPcS4 delivery, but also exhibit enhanced singlet oxygen generation effect and photothermal effect to induce cell death directly. Moreover, AlPcS4 complex with cationic liposomes shows the potent inhibition effect because of its optimal AlPcS4 delivery efficiency and ability to block serum albumin. In addition, AlPcS4 complex with Pluronic F127 exhibits inferior PDT effect but presents lower cytotoxicity, slower dissociation rate, and longer retention time of incorporated drugs; thus, F127-AlPcS4 is used for prolonged gastric cancer therapy. Conclusion: The described AlPcS4 drug delivery systems provide promising agents for gastric cancer therapy.


Assuntos
Portadores de Fármacos/química , Indóis/administração & dosagem , Nanotubos/química , Compostos Organometálicos/administração & dosagem , Fotoquimioterapia/métodos , Neoplasias Gástricas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Cátions , Linhagem Celular Tumoral , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos/métodos , Fluorescência , Ouro/química , Humanos , Indóis/química , Lipossomos/administração & dosagem , Lipossomos/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/farmacologia , Poloxâmero/administração & dosagem , Poloxâmero/química , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Oxigênio Singlete/metabolismo
15.
Nanotechnology ; 28(42): 425102, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-28767043

RESUMO

Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.


Assuntos
Doxorrubicina , Glutationa/metabolismo , Hipertermia Induzida/métodos , Micelas , Nanopartículas , Neoplasias , Fototerapia/métodos , Semicondutores , Doxorrubicina/química , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/terapia
16.
Int J Nanomedicine ; 12: 5659-5672, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28848345

RESUMO

PURPOSE: Pulsed-laser irradiation of light-absorbing gold nanoparticles (AuNPs) attached to cells transiently increases cell membrane permeability for targeted molecule delivery. Here, we targeted EGFR on the ovarian carcinoma cell line OVCAR-3 with AuNPs. In order to optimize membrane permeability and to demonstrate molecule delivery into adherent OVCAR-3 cells, we systematically investigated different experimental conditions. MATERIALS AND METHODS: AuNPs (30 nm) were functionalized by conjugation of the antibody cetuximab against EGFR. Selective binding of the particles was demonstrated by silver staining, multiphoton imaging, and fluorescence-lifetime imaging. After laser irradiation, membrane permeability of OVCAR-3 cells was studied under different conditions of AuNP concentration, cell-incubation medium, and cell-AuNP incubation time. Membrane permeability and cell viability were evaluated by flow cytometry, measuring propidium iodide and fluorescein isothiocyanate-dextran uptake. RESULTS: Adherently growing OVCAR-3 cells can be effectively targeted with EGFR-AuNP. Laser irradiation led to successful permeabilization, and 150 kDa dextran was successfully delivered into cells with about 70% efficiency. CONCLUSION: Antibody-targeted and laser-irradiated AuNPs can be used to deliver molecules into adherent cells. Efficacy depends not only on laser parameters but also on AuNP:cell ratio, cell-incubation medium, and cell-AuNP incubation time.


Assuntos
Permeabilidade da Membrana Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Ouro/química , Lasers , Nanopartículas Metálicas/química , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Cetuximab/administração & dosagem , Cetuximab/química , Dextranos/farmacocinética , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Feminino , Citometria de Fluxo/métodos , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/farmacocinética , Humanos , Nanopartículas Metálicas/administração & dosagem , Terapia de Alvo Molecular , Propídio/farmacocinética
17.
Nanotechnology ; 28(25): 255101, 2017 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-28561013

RESUMO

Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle's stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.


Assuntos
Doxorrubicina , Ácido Láctico , Nanopartículas , Neoplasias/tratamento farmacológico , Ácido Poliglicólico , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Células Hep G2 , Humanos , Ácido Láctico/química , Ácido Láctico/farmacocinética , Ácido Láctico/farmacologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacocinética , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
18.
J Biomed Opt ; 21(12): 128001, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27978553

RESUMO

Although TiO2 can be used to effectively generate reactive oxygen species (ROS) for photodynamic application, its absorption in the ultraviolet range makes the excitation harmful to tissue. Based on the concept of a sensitized solar cell, TiO2 nanoparticles (NPs) are sensitized by linking with the photosensitizer, HMME, to form HMME-TiO2 nanocomposites (NCs) for demonstrating the photodynamic effects under the illumination of white light. The HMME-TiO2 NCs of different composition ratios are prepared for maximizing the generation of ROS and optimizing the inactivation effect of KB cells. The material characteristics and the ROS generation capability of the HMME-TiO2 NCs with the optimized combination ratio show their merits in a photodynamic process under white light irradiation. The application of such NCs to KB cell experiments results in a higher inactivation efficiency when compared to pure HMME of the same concentration.


Assuntos
Nanocompostos/química , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Porfirinas/química , Titânio/química , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células KB , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Espécies Reativas de Oxigênio , Titânio/farmacologia
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 33(6): 1152-7, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29714981

RESUMO

The new mechanisms of automaticity controlled by the calcium and membrane clocks in sinoatrial node are helpful to revealing the sinus arrhythmia,but the present calcium dynamic model is only on the single cell level.In the present study,a central and peripheral single cell model was developed,and by exponentially changing the cell membrane capacitance,size,conductance and gap junction from the center to the periphery,a two-dimensional inhomogeneous sinus and atrial model was created on the basis of the anatomical structure.Five-point difference and finite element methods were used to process the internal grids and the borders.Irregular borders were defined by creating segment trial functions.Quantitative experiments suggested the consistency of the central and peripheral action potentials with related reports in amplitude,cycle length,maximum diastolic potential and upstroke velocity.Functions of the calcium and membrane clocks on the leading pacemaker site and upstroke velocity as well as the effects of the atrial premature beat on the sinus automaticity were also in good agreement with those in other studies.The developed model is helpful for deeply studying relative roles of the calcium and membrane clocks in automaticity and the relations with electrical activities in atrium.At the same time it will lay the foundation for building three-dimensional sinus and atrial organic models.


Assuntos
Arritmia Sinusal/fisiopatologia , Cálcio/fisiologia , Modelos Cardiovasculares , Nó Sinoatrial/fisiologia , Potenciais de Ação , Relógios Biológicos , Diástole , Átrios do Coração , Humanos , Nó Sinoatrial/fisiopatologia
20.
J Biomed Opt ; 20(5): 51043, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26021715

RESUMO

There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function,singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding.Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX­GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ≤ 50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.


Assuntos
Ácido Aminolevulínico/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Neoplasias Experimentais/tratamento farmacológico , Fotoquimioterapia/métodos , Ácido Aminolevulínico/química , Linhagem Celular Tumoral , Ouro/química , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Nanocápsulas/ultraestrutura , Nanoconjugados/administração & dosagem , Nanoconjugados/química , Nanoconjugados/ultraestrutura , Neoplasias Experimentais/patologia , Fármacos Fotossensibilizantes/administração & dosagem , Resultado do Tratamento
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