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1.
Nanoscale ; 12(16): 8890-8897, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32266902

RESUMO

Selectively attenuating the protection offered by heat shock protein 90 (HSP90), which is indispensable for the stabilization of the essential regulators of cell survival and works as a cell guardian under oxidative stress conditions, is a potential approach to improve the efficiency of cancer therapy. Here, we designed a biodegradable nanoplatform (APCN/BP-FA) based on a Zr(iv)-based porphyrinic porous coordination network (PCN) and black phosphorus (BP) sheets for efficient photodynamic therapy (PDT) by enhancing the accumulation of the nanoplatforms in the tumor area and attenuating the protection of cancer cells. Owing to the favorable degradability of BP, the nanosystem exhibited accelerated the release of the HSP90 inhibitor tanespimycin (17-AAG) and an apparent promotion in the reactive oxygen species (ROS) yield of PCN as well as expedited the degradation of the PCN-laden BP nanoplatforms. Both in vitro and in vivo results revealed that the elevated amounts of ROS and reduced cytoprotection in tumor cells were caused by the nanoplatforms. This strategy may provide a promising method for attenuating cytoprotection to aid efficient photodynamic therapy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31671247

RESUMO

Fluorescent materials exhibiting two-photon induction (TPI) are used for nonlinear optics, bioimaging, and phototherapy. Polymerizations of molecular chromophores to form π-conjugated structures were hindered by the lack of long-range ordering in the structure and strong π-π stacking between the chromophores. Reported here is the rational design of a benzothiadiazole-based covalent organic framework (COF) for promoting TPI and obtaining efficient two-photon induced fluorescence emissions. Characterization and spectroscopic data revealed that the enhancement in TPI performance is attributed to the donor-π-acceptor-π-donor configuration and regular intervals of the chromophores, the large π-conjugation domain, and the long-range order of COF crystals. The crystalline structure of TPI-COF attenuates the π-π stacking interactions between the layers, and overcomes aggregation-caused emission quenching of the chromophores for improving near-infrared two-photon induced fluorescence imaging.

3.
Biomaterials ; 207: 76-88, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30959408

RESUMO

Various negative effects accompanying with the instability of bare liquid metal (LM) nanoparticles, including undesirable spontaneous coalescence, continuous photothermal performance deterioration and difficult multi-step functionalization, severely hinder its applications in biomedical area. In this study, we proposed a new concept of immobilized liquid metal nanoparticles based on a surface mesoporous silica coating strategy (LM@MSN). Strikingly, it was found that unsteady and vulnerable LM nanoparticles after immobilization exhibited enhanced stabilization and sustainable photothermal performance even with a long and repeated light irradiation in acidic environments. Moreover, integrating the properties of easy surface functionalization and high drug loading efficiency from silica shell, immobilized LM nanoparticle was further used for photothermal involved combinational therapy. The classical anticancer drug doxorubicin (DOX) was encapsulated in pores of silica shell and the hyaluronic acid (HA) was decorated on LM@MSN to construct LM@MSN/DOX@HA for tumor targeted combination therapy. Both in vitro and in vivo studies proved that LM@MSN/DOX@HA could significantly inhibit solid tumor growth under near infrared (NIR) irradiation by synergistic photothermal/chemotherapy.

4.
Biomaterials ; 195: 75-85, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30616030

RESUMO

Targeted drug delivery with precisely controlled drug release and activation is highly demanding and challenging for tumor precision therapy. Herein, a biomimetic cascade nanoreactor (designated as Mem@GOx@ZIF-8@BDOX) is constructed for tumor targeted starvation therapy-amplified chemotherapy by assembling tumor cell membrane cloak and glucose oxidase (GOx) onto zeolitic imidazolate framework (ZIF-8) with the loading prodrug of hydrogen peroxide (H2O2)-sensitive BDOX. Biomimetic membrane camouflage affords superior immune evasion and homotypic binding capacities, which significantly enhance the tumor preferential accumulation and uptake for targeted drug delivery. Moreover, GOx-induced glycolysis would cut off glucose supply and metabolism pathways for tumor starvation therapy with the transformation of tumor microenvironments. Importantly, this artificial adjustment could trigger the site-specific BDOX release and activation for cascade amplified tumor chemotherapy regardless of the complexity and variability of tumor physiological environments. Both in vitro and in vivo investigations indicate that the biomimetic cascade nanoreactor could remarkably improve the therapeutic efficacy with minimized side effects through the synergistic starvation therapy and chemotherapy. This biomimetic cascade strategy would contribute to developing intelligent drug delivery systems for tumor precision therapy.


Assuntos
Biomimética/métodos , Nanopartículas/química , Animais , Glucose Oxidase/química , Humanos , Peróxido de Hidrogênio/química , Estruturas Metalorgânicas , Pró-Fármacos/química , Zeolitas/química
5.
Biomaterials ; 194: 84-93, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30583151

RESUMO

This paper reported on a two-photon excited nanocomposite FCRH to overcome tumor hypoxia for enhanced photodynamic therapy (PDT). Through modified by ruthenium (Ⅱ) complex (Ru(bpy)32+) and hyperbranched conjugated copolymer with poly (ethylene glycol) arms (HOP), the water-splitting mediated O2 generation can be triggered via two-photon irradiation from iron-doped carbon nitride (Fe-C3N4) for the first time. While exposured to two-photon laser, Ru(bpy)32+ was activated to generate singlet oxygen (1O2) and Fe-C3N4 was triggered to split water for oxygen supply in the mean time. Owing to the injection of photoinduced electrons from excited Ru(bpy)32+ to Fe-C3N4, O2 generation by Fe-C3N4 was significantly accelerated. After accumulation of the nanocomposite by enhanced permeability and retention (EPR) effect, FCRH was demonstrated to alleviate the tumorous hypoxia and consequently enhance the antitumor efficacy of PDT. Furthermore, tumor metabolism evaluations explained the capability of the nanocomposite in reducing intratumoral hypoxia. Our results provide a new diagram for ameliorating the hypoxic tumor microenvironment and accelerating 1O2 generation under two-photon excitation, which will find great potential for spatiotemporally controlled tumor treatment in vivo.


Assuntos
Neoplasias Mamárias Experimentais/tratamento farmacológico , Nanocompostos/uso terapêutico , Nitrilos/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Rutênio/uso terapêutico , Hipóxia Tumoral/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Feminino , Neoplasias Mamárias Experimentais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Oxigênio Singlete/metabolismo , Microambiente Tumoral/efeitos dos fármacos
6.
Nano Lett ; 18(11): 6804-6811, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30350653

RESUMO

Free radicals have emerged as new-type and promising candidates for hypoxic tumor treatment, and further study of their therapeutic mechanism by real-time imaging is of great importance to explore their biomedical applications. Herein, we present a smart free-radical generator AuNC-V057-TPP for hypoxic tumor therapy; the AuNC-V057-TPP not only exhibits good therapeutic effect under both hypoxic and normoxic conditions but also can monitor the release of free radicals in real-time both in vitro and in vivo. What is more, with the mitochondria-targeting ability, the AuNC-V057-TPP is demonstrated with improved antitumor efficacy through enhanced free radical level in mitochondria, which leads to mitochondrial membrane damage and ATP production reduction and finally induces cancer cell apoptosis.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Radicais Livres/metabolismo , Ouro , Neoplasias Mamárias Animais , Nanopartículas Metálicas , Mitocôndrias , Imagem Molecular/métodos , Hipóxia Tumoral , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Ouro/química , Ouro/farmacologia , Neoplasias Mamárias Animais/diagnóstico por imagem , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/terapia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia
7.
Biomaterials ; 161: 81-94, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29421565

RESUMO

Nowadays, cell membrane targeting therapy has drawn much attention for its high anti-tumor effect by avoiding the cellular barriers. In this study, therapeutic agent conjugated chimeric peptide (Cp) was anchored in cracked cancer cell membranes (CCCM) to construct a self-delivery membrane system (M-Cp), which could relize precise cell membrane targeting therapy. It was found that compared with Cp, M-Cp could target to the cancer cell membrane with longer retention time, which is very crucial for in vivo applications. And the superior cell membrane targeting ability was attributed to the specific proteins (focal adhesion proteins, focal adhesion kinase, RHO family proteins, and integrin) on the CCCM surface. Importantly, the M-Cp could promote tumor-specific immune response, which further enhanced anti-tumor effect when combined with therapeutic agents in M-Cp. What's more, this self-delivery membrane system could be used as a template for cell membrane targeting therapy by changing the therapeutic agents as well as the CCCM, and this strategy would open a new window for various cell membrane targeting therapy.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Peptídeos/química , Animais , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Humanos , Modelos Biológicos
8.
Biomaterials ; 151: 1-12, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29040939

RESUMO

In this report, a biomimetic theranostic oxygen (O2)-meter (cancer cell membrane@Pt(II) porphyrinic-metal organic framework, designated as mPPt) was constructed for cancer targeted and phosphorescence image-guided photodynamic therapy (PDT). mPPt presents high photosensitizers (PSs) loading and evitable self-quenching behaviors for favorable biological O2 sensing and PDT. Besides, endowed by the surface functionalization of cancer cell membrane, the homotypic targeting and immune escape abilities of mPPt could dramatically enhance its cancer targeting ability. Importantly, the O2-dependent phosphorescence responsibility of mPPt could be employed to pre-evaluate the real time O2 level in situ and guide the PDT under light irradiation. A significant anticancer effect is observed after intravenous injection of mPPt and subsequent treatment with PDT with no obvious side effects. As a versatile platform for cell imaging, O2 fluctuation monitoring as well as PDT, this biomimetic O2-meter exhibits great potential for biological analysis and personalized cancer theranostics.


Assuntos
Antineoplásicos/química , Estruturas Metalorgânicas/química , Oxigênio/análise , Fotoquimioterapia/métodos , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/farmacologia , Transporte Biológico , Biomimética/métodos , Linhagem Celular Tumoral , Complexos de Coordenação/química , Fluorescência , Haplorrinos , Humanos , Luz , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Imagem Óptica/métodos , Oxigênio/metabolismo , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Platina/química , Porfirinas/química , Propriedades de Superfície
9.
ACS Nano ; 11(7): 7006-7018, 2017 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-28665106

RESUMO

Selectively cuting off the nutrient supply and the metabolism pathways of cancer cells would be a promising approach to improve the efficiency of cancer treatment. Here, a cancer targeted cascade bioreactor (designated as mCGP) was constructed for synergistic starvation and photodynamic therapy (PDT) by embedding glucose oxidase (GOx) and catalase in the cancer cell membrane-camouflaged porphyrin metal-organic framework (MOF) of PCN-224 (PCN stands for porous coordination network). Due to biomimetic surface functionalization, the immune escape and homotypic targeting behaviors of mCGP would dramatically enhance its cancer targeting and retention abilities. Once internalized by cancer cells, mCGP was found to promote microenvironmental oxygenation by catalyzing the endogenous hydrogen peroxide (H2O2) to produce oxygen (O2), which would subsequently accelerate the decomposition of intracellular glucose and enhance the production of cytotoxic singlet oxygen (1O2) under light irradiation. Consequently, mCGP displayed amplified synergistic therapeutic effects of long-term cancer starvation therapy and robust PDT, which would efficiently inhibit the cancer growth after a single administration. This cascade bioreactor would further facilitate the development of complementary modes for spatiotemporally controlled cancer treatment.


Assuntos
Catalase/uso terapêutico , Glucose Oxidase/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/uso terapêutico , Animais , Células COS , Catalase/metabolismo , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Chlorocebus aethiops , Glucose/metabolismo , Glucose Oxidase/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Oxigênio/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Porfirinas/química , Células RAW 264.7
10.
Anal Chem ; 89(8): 4349-4354, 2017 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-28365980

RESUMO

A novel single-molecular fluorescent probe was developed for spatiotemporal matrix metalloproteinase-2 (MMP-2) and caspase-3 imaging with distinct fluorescence signals. Due to the multi-Förster resonance energy transfer (FRET) processes, the probe could respond to MMP-2 and caspase-3 independently with high signal-to-noise ratio. Moreover, the overexpression of MMP-2 in cancer cell lines and the cisplatin induced cell apoptosis were spatiotemporal imaged with distinct fluorescence emissions. Because of the independent process of the probe for MMP-2 and caspase-3 imaging, the probe could meet the demands for precise disease diagnosis and cancer theranostic applications, which could extensively simplify the processes for precise cancer diagnosis and imaging.


Assuntos
Caspase 3/metabolismo , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Metaloproteinase 2 da Matriz/metabolismo , Animais , Células COS , Caspase 3/química , Linhagem Celular Tumoral , Chlorocebus aethiops , Citometria de Fluxo , Humanos , Metaloproteinase 2 da Matriz/química , Microscopia Confocal
11.
Biomaterials ; 104: 297-309, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27475726

RESUMO

Feedback imaging-guided precise photodynamic therapy (PDT) can facilitate the development of personalized medicine. In this work, a Förster resonance energy transfer (FRET) based theranostic probe was fabricated for simultaneous tumor targeting PDT and ratiometric imaging of the therapeutic effect. The theranostic probe (designated as P-PpIX) was comprised of a targeting moiety, a caspase-3 responsive linker, a FRET fluorophore pair and a photosensitizer. It was found that P-PpIX exhibited low intrinsic background fluorescence due to the high FRET quenching efficiency. The Arg-Gly-Asp (RGD) targeting moiety allowed P-PpIX to selectively accumulate in αvß3 integrin overexpressed tumor cells. Upon photo irradiation, the PDT effect of P-PpIX could induce cell death with apoptosis related mechanism, and the activated caspase-3 would subsequently cleave the Asp-Glu-Val-Asp (DEVD) peptide sequence to terminate the intramolecular FRET process. The activated caspase-3 expression and the real time therapeutic efficacy could be precisely assessed in situ by the fluorescence intensity ratio of the released 5(6)-carboxylfluorescein (FAM, reporter fluorescence) and protoporphyrin IX (PpIX, internal reference fluorescence). This novel ratiometric theranostic probe could provide the real-time feedback for precise PDT.


Assuntos
Nanocápsulas/química , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Protoporfirinas/administração & dosagem , Nanomedicina Teranóstica/métodos , Animais , Células COS , Chlorocebus aethiops , Monitoramento de Medicamentos/métodos , Transferência Ressonante de Energia de Fluorescência/métodos , Nanocápsulas/ultraestrutura , Neoplasias Experimentais/metabolismo , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Protoporfirinas/química , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento
12.
ACS Appl Mater Interfaces ; 7(51): 28319-29, 2015 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-26634784

RESUMO

In this paper, we aimed to develop a conjugate of matrix metalloproteinases-2 (MMP-2)-sensitive activable cell-penetrating peptide (R9GPLGLAGE8, ACPP) with protoporphyrin (PpIX) for tumor-targeting photodynamic therapy. In normal tissue, the cell-penetrating function of polycationic CPP (R9) would be blocked by a polyanionic peptide (E8) through intramolecular electrostatic attraction. Once exposed to MMP-2 existing at the tumor site, proteolysis of the oligopeptide linker (GPLGLAG) between the CPP and the polyanionic peptide would dissociate the inhibitory polyanions and release CPP-PpIX for photodynamic therapy (PDT). It was found that after tail vein injection the ACPP-PpIX conjugate could accumulate effectively at the tumor site with the fluorescence enhancement which was beneficial for tumor diagnosis and image-guided PDT. After further administration with irradiation, both the solid tumor size and weight had a significant suppression (reduced by more than 90%) with a low systemic toxicity. This ACPP-PpIX conjugate delivery system activated by MMP-2 would be a promising strategy for tumor-targeted treatment.


Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias/tratamento farmacológico , Protoporfirinas/química , Animais , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/metabolismo , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/enzimologia , Fotoquimioterapia , Protoporfirinas/administração & dosagem , Protoporfirinas/metabolismo
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