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1.
Nat Biomed Eng ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632226

RESUMO

Patients with kidney failure commonly require dialysis to remove nitrogenous wastes and to reduce burden to the kidney. Here, we show that a bacterial cocktail orally delivered in animals with kidney injury can metabolize blood nitrogenous waste products before they diffuse through the intestinal mucosal barrier. The microbial cocktail consists of three strains of bacteria isolated from faecal microbiota that metabolize urea and creatinine into amino acids, and is encapsulated in calcium alginate microspheres coated with a polydopamine layer that is selectively permeable to small-molecule nitrogenous wastes. In murine models of acute kidney injury and chronic kidney failure, and in porcine kidney failure models, the encapsulated microbial cocktail significantly reduced urea and creatinine concentrations in blood, and did not lead to any adverse effects.

2.
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.

3.
Adv Mater ; 32(16): e2000376, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32134530

RESUMO

Traditional phototherapies face the issue that the insufficient penetration of light means it is difficult to reach deep lesions, which greatly reduces the feasibility of cancer therapy. Here, an implantable nitric oxide (NO)-release device is developed to achieve long-term, long-distance, remote-controllable gas therapy for cancer. The device consists of a wirelessly powered light-emitting diode (wLED) and S-nitrosoglutathione encapsulated with poly(dimethylsiloxane) (PDMS), obtaining the NO-release wLED (NO-wLED). It is found that NO release from the NO-wLED can be triggered by wireless charging and the concentration of produced NO reaches 0.43 × 10-6 m min-1 , which can achieve a killing effect on cancer cells. In vivo anticancer experiments exhibit obvious inhibitory effect on the growth of orthotopic cancer when the implanted NO-wLED is irradiated by wireless charging. In addition, recurrence of cancer can be prevented by NO produced from the NO-wLED after surgery. By illumination in the body, this strategy overcomes the poor penetration and long-wavelength dependence of traditional phototherapies, which also provides a promising approach for in vivo gas therapy remote-controlled by wireless charging.

4.
ACS Nano ; 13(12): 14230-14240, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31714733

RESUMO

Tumorous vasculature plays key roles in sustaining tumor growth. Vascular disruption is accompanied by internal coagulation along with platelet recruitment and the resulting suppression of oxygen supply. We intend to artificially create this physiological process to establish the mutual feedback between vascular disruption and platelet-mimicking biotaxis for the cascade amplification of hypoxia-dependent therapy. To prove this concept, mesoporous silica nanoparticles are co-loaded with a hypoxia-activated prodrug (HAP) and a vessel-disruptive agent and then coated with platelet membranes. Upon entering into tumors, our nanotherapeutic can disrupt local vasculature for tumor inhibition. This platelet membrane-coated nanoplatform shares the hemorrhage-tropic function with parental platelets and can be persistently recruited by the vasculature-disrupted tumors. In this way, the intratumoral vascular disruption and tumor targeting are biologically interdependent and mutually reinforced. Relying on this mutual feedback, tumorous hypoxia was largely promoted by more than 20-fold, accounting for the effective recovery of the HAP's cytotoxicity. Consequently, our bioinspired nanodesign has demonstrated highly specific and effective antitumor potency via the biologically driven cooperation among intratumoral vascular disruption, platelet-mimicking biotaxis, cascade hypoxia amplification, and hypoxia-sensitive chemotherapy. This study offers a paradigm of correlating the therapeutic design with the physiologically occurring events to achieve better therapy performance.

5.
Adv Sci (Weinh) ; 6(17): 1900835, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31508286

RESUMO

Metal ions are of significant importance in biomedical science. This study reports a new concept of cytomembrane-mediated biospecific transport of metal ions without using any other materials. For the first time, cytomembranes are exploited for two-step conjugation with metal ions to provide hybrid nanomaterials. The innate biofunction of cell membranes renders the hybrids with superior advantages over common vehicles for metal ions, including excellent biocompatibility, low immunogenic risk, and particularly specific biotargeting functionality. As a proof-of-concept demonstration, cancer cell membranes are used for in vivo delivery of various metal ions, including ruthenium, europium, iron, and manganese, providing a series of tumor-targeted nanohybrids capable of photothermal therapy/imaging, magnetic resonance imaging, photoacoustic imaging, and fluorescence imaging with improved performances. In addition, the special structure of the cell membrane allows easy accommodation of small-molecular agents within the nanohybrids for effective chemotherapy. This study provides a new class of metal-ion-included nanomaterials with versatile biofunctions and offers a novel solution to address the important challenge in the field of in vivo targeted delivery of metal ions.

6.
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.

7.
Nat Commun ; 10(1): 3199, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324770

RESUMO

Most cancer vaccines are unsuccessful in eliciting clinically relevant effects. Without using exogenous antigens and adoptive cells, we show a concept of utilizing biologically reprogrammed cytomembranes of the fused cells (FCs) derived from dendritic cells (DCs) and cancer cells as tumor vaccines. The fusion of immunologically interrelated two types of cells results in strong expression of the whole tumor antigen complexes and the immunological co-stimulatory molecules on cytomembranes (FMs), allowing the nanoparticle-supported FM (NP@FM) to function like antigen presenting cells (APCs) for T cell immunoactivation. Moreover, tumor-antigen bearing NP@FM can be bio-recognized by DCs to induce DC-mediated T cell immunoactivation. The combination of these two immunoactivation pathways offers powerful antitumor immunoresponse. Through mimicking both APCs and cancer cells, this cytomembrane vaccine strategy can develop various vaccines toward multiple tumor types and provide chances for accommodating diverse functions originating from the supporters.


Assuntos
Apresentação do Antígeno/imunologia , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Membrana Celular/imunologia , Nanopartículas/uso terapêutico , Animais , Fusão Celular , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Feminino , Imunoterapia , Ativação Linfocitária , Neoplasias Mamárias Experimentais/imunologia , Neoplasias Mamárias Experimentais/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia , Transcriptoma , Transplante Heterólogo
8.
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.

9.
Adv Mater ; 31(18): e1900499, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30907473

RESUMO

Using the cytomembranes (FMs) of hybrid cells acquired from the fusion of cancer and dendritic cells (DCs), this study offers a biologically derived platform for the combination of immunotherapy and traditional oncotherapy approaches. Due to the immunoactivation implicated in the cellular fusion, FMs can effectively express whole cancer antigens and immunological co-stimulatory molecules for robust immunotherapy. FMs share the tumor's self-targeting character with the parent cancer cells. In bilateral tumor-bearing mouse models, the FM-coated nanophotosensitizer causes durable immunoresponse to inhibit the rebound of primary tumors post-nanophotosensitizer-induced photodynamic therapy (PDT). The FM-induced immunotherapy displays ultrahigh antitumor effects even comparable to that of PDT. On the other hand, PDT toward primary tumors enhances the immunotherapy-caused regression of the irradiation-free distant tumors. Consequently, both the primary and the distant tumors are almost completely eliminated. This tumor-specific immunotherapy-based nanoplatform is potentially expandable to multiple tumor types and readily equipped with diverse functions owing to the flexible nanoparticle options.


Assuntos
Membrana Celular/química , Células Dendríticas/citologia , Imunoterapia , Nanoestruturas/química , Animais , Anticorpos/química , Anticorpos/imunologia , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Antígenos de Histocompatibilidade Classe II/imunologia , Receptores de Hialuronatos/imunologia , Estruturas Metalorgânicas/química , Camundongos , Camundongos Nus , Nanoestruturas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/química , Porfirinas/uso terapêutico , Transplante Heterólogo , Zircônio/química
10.
Adv Mater ; 31(16): e1808278, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803049

RESUMO

Synthetic biology based on bacteria has been displayed in antitumor therapy and shown good performance. In this study, an engineered bacterium Escherichia coli MG1655 is designed with NDH-2 enzyme (respiratory chain enzyme II) overexpression (Ec-pE), which can colonize in tumor regions and increase localized H2 O2 generation. Following from this, magnetic Fe3 O4 nanoparticles are covalently linked to bacteria to act as a catalyst for a Fenton-like reaction, which converts H2 O2 to toxic hydroxyl radicals (•OH) for tumor therapy. In this constructed bioreactor, the Fenton-like reaction occurs with sustainably synthesized H2 O2 produced by engineered bacteria, and severe tumor apoptosis is induced via the produced toxic •OH. These results show that this bioreactor can achieve effective tumor colonization, and realize a self-supplied therapeutic Fenton-like reaction without additional H2 O2 provision.


Assuntos
Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Neoplasias/terapia , Animais , Apoptose , Reatores Biológicos , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Nanopartículas de Magnetita/química , Camundongos Endogâmicos BALB C , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
11.
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
12.
ACS Nano ; 13(2): 1784-1794, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30698953

RESUMO

Hypoxia, a ubiquitously aberrant phenomenon implicated in tumor growth, causes severe tumor resistance to therapeutic interventions. Instead of the currently prevalent solution through intratumoral oxygen supply, we put forward an "O2-economizer" concept by inhibiting the O2 consumption of cell respiration to spare endogenous O2 and overcome the hypoxia barrier. A nitric oxide (NO) donor responsible for respiration inhibition and a photosensitizer for photodynamic therapy (PDT) are co-loaded into poly(d,l-lactide- co-glycolide) nanovesicles to provide a PDT-specific O2 economizer. Once accumulating in tumors and subsequently responding to the locally reductive environment, the carried NO donor undergoes breakdown to produce NO for inhibiting cellular respiration, allowing more O2 in tumor cells to support the profound enhancement of PDT. Depending on the biochemical reallocation of cellular oxygen resource, this O2-economizer concept offers a way to address the important issue of hypoxia-induced tumor resistance to therapeutic interventions, including but not limited to PDT.

13.
Nano Lett ; 18(12): 7609-7618, 2018 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-30383966

RESUMO

Chemodynamic therapy (CDT) can efficiently destroy tumor cells via Fenton reaction in the presence of H2O2 and a robust catalyst. However, it has faced severe challenges including the limited amounts of H2O2 and inefficiency of catalysts. Here, an adenosine triphosphate (ATP)-responsive autocatalytic Fenton nanosystem (GOx@ZIF@MPN), incorporated with glucose oxidase (GOx) in zeolitic imidazolate framework (ZIF) and then coated with metal polyphenol network (MPN), was designed and synthesized for tumor ablation with self-supplied H2O2 and TA-mediated acceleration of Fe(III)/Fe(II) conversion. In the ATP-overexpressed tumor cells, the outer shell MPN of GOx@ZIF@MPN was degraded into Fe(III) and tannic acid (TA) and the internal GOx was exposed. Then, GOx reacted with the endogenous glucose to produce plenty of H2O2, and TA reduced Fe(III) to Fe(II), which is a much more vigorous catalyst for the Fenton reaction. Subsequently, self-produced H2O2 was catalyzed by Fe(II) to generate highly toxic hydroxyl radical (•OH) and Fe(III). The produced Fe(III) with low catalytic activity was quickly reduced to reactive Fe(II) mediated by TA, forming an accelerated Fe(III)/Fe(II) conversion to guarantee efficient Fenton reaction-mediated CDT. This autocatalytic Fenton nanosystem might provide a good paradigm for effective tumor treatment.

14.
Adv Mater ; 30(52): e1805038, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30378187

RESUMO

Adenosine triphosphate (ATP) is the most important immediate energy source for driving intracellular biochemical reactions in nearly all life forms. Controllable generation of ATP in life is still an unrealized goal. Here, thylakoid fragments are recombined with lipid molecules to synthesize a synthetic/biological hybrid proteoliposome, named highly efficient life-support intracellular opto-driven system (HELIOS) for the generation of ATP. With red light irradiation, HELIOS can improve the intracellular ATP concentration to 1.38-2.45 times in various cell lines. Moreover, it is noticed that HELIOS-mediated ATP generation can comprehensively promote cell functions such as protein synthesis and insulin secretion. At organ and individual levels, it is also proved that HELIOS can rescue a mouse heart from myocardial infarction and sustain life of fasting zebrafish Danio rerio models. The photo-powered artificial organelle can deepen our understanding of metabolism and enable the development of optical therapy that targets intracellular energy supply.


Assuntos
Trifosfato de Adenosina , Células Artificiais , Infarto do Miocárdio/terapia , Fototerapia , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Animais , Animais Geneticamente Modificados , Células Artificiais/química , Células Artificiais/efeitos da radiação , Células COS , Chlorocebus aethiops , Modelos Animais de Doenças , Jejum/metabolismo , Glucose/deficiência , Espaço Intracelular/metabolismo , Luz , Camundongos , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Processos Fotoquímicos , Ratos Sprague-Dawley , Peixe-Zebra
15.
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
16.
Small ; 14(50): e1803602, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30370690

RESUMO

By integrating the characteristics of each therapy modality and material chemistry, a multitherapy modality is put forward: tumor starvation triggered synergism with sensitized chemotherapy. Following starvation-induced amplification of pathological abnormalities in tumors, chemotherapy is arranged to be locally activated and accurately reinforced to perfect multitherapy synergism from spatial and temporal perspectives. To this end, glucose oxidase (GOD) and a hypoxic prodrug of tirapazamine (TPZ) are loaded in acidity-decomposable calcium carbonate (CaCO3 ) nanoparticles concurrently tethered by hyaluronic acid. This hybrid nanotherapeutic shows a strong tendency to accumulate in tumors postinjection due to the cooperation between passive and active targeting mechanisms. The GOD-driven oxidation reaction deprives tumors of glucose for starvation therapy and concomitantly induces tumorous abnormality amplifications including elevated acidity and exacerbated hypoxia. Programmatically, the acidity amplification causes CaCO3 decomposition, offering not only spatial control over the liberation of embedded TPZ just within tumors but also the temporal control over timely chemotherapy initiation to match the occurrence of hypoxia amplification and thus benefiting perfect synergism between starvation therapy and chemotherapy.


Assuntos
Antineoplásicos/química , Carbonato de Cálcio/química , Nanopartículas/química , Pró-Fármacos/química , Tirapazamina/química , Glucose Oxidase/metabolismo , Ácido Hialurônico/química
17.
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
18.
Small ; 14(28): e1801120, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29882235

RESUMO

Hypoxia is reported to participate in tumor progression, promote drug resistance, and immune escape within tumor microenvironment, and thus impair therapeutic effects including the chemotherapy and advanced immunotherapy. Here, a multifunctional biomimetic core-shell nanoplatform is reported for improving synergetic chemotherapy and immunotherapy. Based on the properties including good biodegradability and functionalities, the pH-sensitive zeolitic imidazolate framework 8 embedded with catalase and doxorubicin constructs the core and serves as an oxygen generator and drug reservoir. Murine melanoma cell membrane coating on the core provides tumor targeting ability and elicits an immune response due to abundance of antigens. It is demonstrated that this biomimetic core-shell nanoplatform with oxygen generation can be partial to accumulate in tumor and downregulate the expression of hypoxia-inducible factor 1α, which can further enhance the therapeutic effects of chemotherapy and reduce the expression of programmed death ligand 1 (PD-L1). Combined with immune checkpoints blockade therapy by programmed death 1 (PD-1) antibody, the dual inhibition of the PD-1/PD-L1 axis elicits significant immune response and presents a robust effect in lengthening tumor recurrent time and inhibiting tumor metastasis. Consequently, the multifunctional nanoplatform provides a potential strategy of synergetic chemotherapy and immunotherapy.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/metabolismo , Biomimética/métodos , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais , Hipóxia Tumoral/efeitos dos fármacos , Animais , Linfócitos T CD8-Positivos/metabolismo , Catalase/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Doxorrubicina/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Imidazóis/química , Camundongos Endogâmicos C57BL , Nanopartículas/química , Nanopartículas/ultraestrutura , Neoplasias/imunologia , Neoplasias/patologia , Oxigênio/farmacologia , Zeolitas/química
19.
Adv Mater ; 30(27): e1800836, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29782675

RESUMO

With the prominent progress of biomedical engineering, materials with high biocompatibility and versatile functions are urgently needed. So far, hierarchical structures in nature have shed some light on the design of high performance materials both in concept and implementation. Inspired by these, the hierarchical micro-/nanostructures of human hair are explored and human hair is further broken into hierarchical microparticles (HMP) and hierarchical nanoparticles (HNP) with top-down procedures. Compared with commercialized carriers, such as liposomes or albumin nanoparticles, the obtained particles exhibit high hemocompatibility and negligible immunogenicity. Furthermore, these materials also display attentional abilities in the aspects of light absorption and free radical scavenging. It is found that HMP and HNP can prevent skin from UV-induced damage and relieve symptoms of cataract in vitro. Besides, both HMP and HNP show satisfactory photothermal conversion ability. By using microcomputed tomography and intravital fluorescence microscopy, it is found that warfarin-loaded HMP can rescue mice from vein thrombosis. In another aspect, HNP modified with tumor targeted aptamers exhibit dramatic antineoplastic effect, and suppress 96.8% of tumor growth in vivo. Thus, the multifaceted materials described here might provide a new tool for addressing biomedical challenges.


Assuntos
Nanoestruturas , Animais , Antineoplásicos , Cabelo , Humanos , Camundongos , Nanopartículas , Microtomografia por Raio-X
20.
ACS Nano ; 12(6): 6218-6227, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29791792

RESUMO

Tumor hypoxia has attained the status of a core hallmark of cancer that globally affects the entire tumor phenotype. Reversing tumor hypoxia might offer alternative therapeutic opportunities for current anticancer therapies. In this research, a photosynthetic leaf-inspired abiotic/biotic nano-thylakoid (PLANT) system was designed by fusing the thylakoid membrane with synthetic nanoparticles for efficient O2 generation in vivo. Under 660 nm laser irradiation, the PLANT system exhibited intracellular O2 generation and the anaerobic respiration of the multicellular tumor spheroid was suppressed by PLANT as well. In vivo, it was found that PLANT could not only normalize the entire metabolic network but also adjust the abnormal structure and function of the tumor vasculature. It was demonstrated that PLANT could significantly enhance the efficacy of phototherapy or antiangiogenesis therapy. This facile approach for normalizing the tumor microenvironment will find great potential in tumor therapy.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Nanopartículas/química , Neovascularização Patológica/terapia , Fotossíntese , Tilacoides/metabolismo , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Oxigênio/metabolismo , Fototerapia/métodos , Esferoides Celulares/metabolismo
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