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1.
Nanoscale ; 12(5): 2966-2972, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31971210

RESUMO

Lactate, the main contributor to the acidic tumor microenvironment, not only promotes the proliferation of tumor cells, but also closely relates to tumor invasion and metastasis. Here, a tumor targeting nanoplatform, designated as Me&Flu@MSN@MnO2-FA, was fabricated for effective tumor suppression and anti-metastasis by interfering with lactate metabolism of tumor cells. Metformin (Me) and fluvastatin sodium (Flu) were incorporated into MnO2-coated mesoporous silicon nanoparticles (MSNs), the synergism between Me and Flu can modulate the pyruvate metabolic pathway to produce more lactate, and concurrently inhibit lactate efflux to induce intracellular acidosis to kill tumor cells. As a result of the restricted lactate efflux, the extracellular lactate concentration is reduced, and the ability of the tumor cells to migrate is also weakened. This ingenious strategy based on Me&Flu@MSN@MnO2-FA showed an obvious inhibitory effect on tumor growth and resistance to metastasis.

2.
J Control Release ; 320: 159-167, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31978443

RESUMO

Glucose-responsive insulin delivery system mimicking the function of pancreatic ß-cells to maintain blood glucose homeostasis would effectively alleviate diabetes. Here, a new glucose-responsive delivery (ZIF@Ins&GOx) for self-regulated insulin release was constructed by encapsulating insulin and glucose oxidase (GOx) into pH-sensitive zeolitic imidazole framework-8 (ZIF-8) nanocrystals. After entering the cavities of ZIF-8, glucose can be oxidized into gluconic acid by GOx, causing a decrease in local pH. Then, ZIF-8 nanocrystals would be degraded under the acidic microenvironment that in turn triggers the release of insulin in a glucose responsive fashion. In vitro studies indicated that the biological activity of insulin could be protected by the rigid structure of ZIF-8 and the release of insulin could be modulated in response to glucose concentrations. In vivo experiments demonstrated that a single subcutaneous injection of the ZIF@Ins&GOx would facilitate the stabilization of blood glucose level of normoglycemic state for up to 72 h in type 1 diabetes (T1D). The multifunctional insulin delivery system shows a new proof-of-concept for T1D treatment by using ZIF-8 nanocrystals loaded with insulin and enzyme.

3.
Biomaterials ; 224: 119500, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31557591

RESUMO

Redox homeostasis inside malignant cells is a defense mechanism against the reactive oxygen species (ROS)-induced therapy means, but little importance has been paid to this innate barrier. The present study intends to make cancer cells more sensitive to the ROS-induced therapy by disturbing cellular redox homeostasis. To verify this concept, a porous metal-organic framework (MOF) serves not only as the photodynamic therapy (PDT) agent but also as the carrier to transport alkaloid piperlongumine (PL), a thioredoxin reductase (TrxR) inhibitor used to disturb cellular redox homeostasis. The PL-loaded MOF was further coated with cancer cell membranes to gain homologous tumor-targeting capability. Inside tumor cells, the released PL can effectively block the TrxR-mediated ROS elimination pathway. The resultant data show that compared to traditional PDT alone, the combination of PDT and TrxR inhibition causes profound promotions in cellular ROS level by about 1.6 times, in cytotoxicity by about 2 times, and in cellular apoptosis/necrosis rate by about 3 times. Consequently, this strategy based on the interference with cellular redox homeostasis has demonstrated high potency to improve the anticancer PDT performance, adumbrating a new way to boost the power of ROS-induced therapy.

4.
Biomaterials ; 223: 119472, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31499254

RESUMO

Inflammation during photothermal therapy (PTT) of tumor usually results in adverse consequences. Here, a biomembrane camouflaged nanomedicine (mPDAB) containing polydopamine and ammonia borane was designed to enhance PTT efficacy and mitigate inflammation. Polydopamine, a biocompatible photothermal agent, can effectively convert light into heat for PTT. Ammonia borane was linked to the surface of polydopamine through the interaction of hydrogen bonding, which could destroy redox homoeostasis in tumor cells and reduce inflammation by H2 release in tumor microenvironment. Owing to the same origin of outer biomembranes, mPDAB showed excellent tumor accumulation and low systemic toxicity in a breast tumor model. Excellent PTT efficacy and inflammation reduction made the mPDAB completely eliminate the primary tumors, while also restraining the outgrowth of distant dormant tumors. The biomimetic nanomedicine shows potentials as a universal inflammation-self-alleviated platform to ameliorate inflammation-related disease treatment, including but not limited to PTT for tumor.

5.
Biomaterials ; 217: 119303, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31271859

RESUMO

Here, a highly cooperative liquid metal nanoparticle-enzyme (LM@GOX) was constructed for combinational starvation/photothermal therapy of tumor. It was found that the enzyme activity of glucose oxidase (GOX) could be strengthened along with the increased temperature within a given range and its optimal activity is around about 43-60 °C. Utilizing the photothermal conversion ability of liquid metal (LM), the GOX catalytic efficiency could be photo-controlled with improved starvation therapeutic efficiency. Furthermore, due to the accelerating blood flow during the photothermal therapy (PTT), the hypoxic situation in tumor tissues could also be relieved, which would contribute to conquering the hypoxia-suppressed GOX catalysis. In the meanwhile, the severe thermo-resistance of tumor cells during PTT process could be overcome by GOX induced decrease of adenosine triphosphate (ATP) and heat shock proteins (HSPs) level, eventually leading to an improved therapeutic effect of PTT. Both in vitro and in vivo studies proved that LM@GOX could significantly inhibit the growth of solid tumor under NIR illumination by a win-win cooperative starvation/photothermal therapy.

6.
Biomaterials ; 207: 76-88, 2019 Jul.
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.

7.
Adv Mater ; 31(15): e1807211, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803083

RESUMO

To engineer patient-derived cells into therapy-purposed biologics is a promising solution to realize personalized treatments. Without using gene-editing technology, a live cell-typed therapeutic is engineered for tumor treatment by artificially reprogramming macrophages with hyaluronic acid-decorated superparamagnetic iron oxide nanoparticles (HIONs). This nanoparticle-assisted cell-reprogramming strategy demonstrates profound advantages, due to the combined contributions from the biological regulation of HIONs and the intrinsic nature of macrophages. Firstly, the reprogrammed macrophages present a substantial improvement in their innate capabilities, such as more effective tumor targeting and more efficient generation of bioactive components (e.g., reactive oxygen species, bioactive cytokines) to suppress tumor growth. Furthermore, this cell therapeutic exhibits cytostatic/proapoptotic effects specific to cancer cells. Secondly, HIONs enable macrophages more resistant to the intratumoral immunosuppressive environment. Thirdly, the macrophages are endowed with a strong ability to prime in situ protumoral M2 macrophages into antitumor M1 phenotype in a paracrine-like manner. Consequently, a synergistic tumor-inhibition effect is achieved. This study shows that engineering nanomaterial-reprogrammed live cells as therapeutic biologics may be a more preferable option to the commonly used approaches where nanomaterials are administrated to induce bioresponse of certain cells in vivo.


Assuntos
Reprogramação Celular , Macrófagos/metabolismo , Animais , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Macrófagos/imunologia , Nanopartículas de Magnetita , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/imunologia , Neoplasias/terapia , Microambiente Tumoral/imunologia
8.
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
9.
Adv Mater ; 30(35): e1802006, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30015997

RESUMO

Extreme hypoxia of tumors represents the most notable barrier against the advance of tumor treatments. Inspired by the biological nature of red blood cells (RBCs) as the primary oxygen supplier in mammals, an aggressive man-made RBC (AmmRBC) is created to combat the hypoxia-mediated resistance of tumors to photodynamic therapy (PDT). Specifically, the complex formed between hemoglobin and enzyme-mimicking polydopamine, and polydopamine-carried photosensitizer is encapsulated inside the biovesicle that is engineered from the recombined RBC membranes. The mean corpuscular hemoglobin of AmmRBCs reaches about tenfold as high as that of natural RBCs. Owing to the same origin of outer membranes, AmmRBCs share excellent biocompatibility with parent RBCs. The introduced polydopamine plays the role of the antioxidative enzymes existing inside RBCs to effectively prevent the oxygen-carrying hemoglobin from the oxidation damage during the circulation. This biomimetic engineering can accumulate in tumors, permit in situ efficient oxygen supply, and impose strong PDT efficacy toward the extremely hypoxic tumor with complete tumor elimination. The man-made pseudo-RBC shows potentials as a universal oxygen-self-supplied platform to sensitize hypoxia-limited tumor treatment means, including but not limited to PDT. Meanwhile, this study offers ideas to the production of artificial substitutes of packed RBCs for clinical blood transfusion.


Assuntos
Eritrócitos , Animais , Hipóxia Celular , Oxigênio , Fotoquimioterapia , Fármacos Fotossensibilizantes
10.
Small ; 14(20): e1800292, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29665292

RESUMO

This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors.


Assuntos
Hipertermia Induzida , Nanofibras/química , Neoplasias/patologia , Fototerapia , Animais , Morte Celular , Cobre/química , Células Hep G2 , Humanos , Ácido Hialurônico/química , Hialuronoglucosaminidase/metabolismo , Luminescência , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Nanofibras/ultraestrutura , Nanopartículas/química , Nanopartículas/ultraestrutura , Células RAW 264.7 , Esferoides Celulares/patologia , Esferoides Celulares/ultraestrutura , Sulfetos/química , Temperatura Ambiente
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