Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36
Filtrar
1.
Small ; : e2309026, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477698

RESUMO

Hypoxic tumor microenvironment (TME) hampers the application of oxygen (O2 )-dependent photodynamic therapy (PDT) in solid tumors. To address this problem, a biomimetic nanotheranostics (named MMCC@EM) is developed for optical molecular imaging-escorted self-oxygenation PDT. MMCC@EM is synthesized by encapsulating chlorin e6 (Ce6) and catalase (CAT) in metal-organic framework (MOF) nanoparticles with erythrocyte membrane (EM) camouflage. Based on the biomimetic properties of EM, MMCC@EM efficiently accumulates in tumor tissues. The enriched MMCC@EM achieves TME-activatable drug release, thereby releasing CAT and Ce6, and this process can be monitored through fluorescence (FL) imaging. In addition, endogenous hydrogen peroxide (H2 O2 ) will be decomposed by CAT to produce O2 , which can be reflected by the measurement of intratumoral oxygen concentration using photoacoustic (PA) imaging. Such self-oxygenation nanotheranostics effectively mitigate tumor hypoxia and improve the generation of singlet oxygen (1 O2 ). The 1 O2 disrupts mitochondrial function and triggers caspase-3-mediated cellular apoptosis. Furthermore, MMCC@EM triggers immunogenic cell death (ICD) effect, leading to an increased infiltration of cytotoxic T lymphocytes (CTLs) into tumor tissues. As a result, MMCC@EM exhibits good therapeutic effects in 4T1-tumor bearing mice under the navigation of FL/PA duplex imaging.

2.
Angew Chem Int Ed Engl ; 61(42): e202204584, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-35853827

RESUMO

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2 O2 ) generation. Meanwhile, CAT catalyzes H2 O2 into O2 , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.


Assuntos
Nanopartículas , Neoplasias , Catalase , Linhagem Celular Tumoral , Polímeros de Fluorcarboneto , Glucose , Glucose Oxidase , Humanos , Peróxido de Hidrogênio , Lactatos , Neoplasias/patologia
3.
Chem Soc Rev ; 48(10): 2698-2737, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31080987

RESUMO

Calcium phosphates (CaPs) are ubiquitous in nature and vertebrate bones and teeth, and have high biocompatibility and promising applications in various biomedical fields. Nanostructured calcium phosphates (NCaPs) are recognized as promising nanocarriers for drug/gene/protein delivery owing to their high specific surface area, pH-responsive degradability, high drug/gene/protein loading capacity and sustained release performance. In order to control the structure and surface properties of NCaPs, various biomolecules with high biocompatibility such as nucleic acids, proteins, peptides, liposomes and phosphorus-containing biomolecules are used in the synthesis of NCaPs. Moreover, biomolecules play important roles in the synthesis processes, resulting in the formation of various NCaPs with different sizes and morphologies. At room temperature, biomolecules can play the following roles: (1) acting as a biocompatible organic phase to form biomolecule/CaP hybrid nanostructured materials; (2) serving as a biotemplate for the biomimetic mineralization of NCaPs; (3) acting as a biocompatible modifier to coat the surface of NCaPs, preventing their aggregation and increasing their colloidal stability. Under heating conditions, biomolecules can (1) control the crystallization process of NCaPs by forming biomolecule/CaP nanocomposites before heating; (2) prevent the rapid and disordered growth of NCaPs by chelating with Ca2+ ions to form precursors; (3) provide the phosphorus source for the controlled synthesis of NCaPs by using phosphorus-containing biomolecules. This review focuses on the important roles of biomolecules in the synthesis of NCaPs, which are expected to guide the design and controlled synthesis of NCaPs. Moreover, we will also summarize the biomedical applications of NCaPs in nanomedicine and tissue engineering, and discuss their current research trends and future prospects.


Assuntos
Fosfatos de Cálcio/química , Nanocompostos/química , Materiais Biocompatíveis/química , DNA de Cadeia Simples/química , Portadores de Fármacos/química , Química Verde , Humanos , Nanomedicina , Albumina Sérica/química , Engenharia Tecidual
4.
Chem Soc Rev ; 47(2): 357-403, 2018 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-29261194

RESUMO

Calcium-based (CaXs) biomaterials including calcium phosphates, calcium carbonates, calcium silicate and calcium fluoride have been widely utilized in the biomedical field owing to their excellent biocompatibility and biodegradability. In recent years, CaXs biomaterials have been strategically integrated with imaging contrast agents and therapeutic agents for various molecular imaging modalities including fluorescence imaging, magnetic resonance imaging, ultrasound imaging or multimodal imaging, as well as for various therapeutic approaches including chemotherapy, gene therapy, hyperthermia therapy, photodynamic therapy, radiation therapy, or combination therapy, even imaging-guided therapy. Compared with other inorganic biomaterials such as silica-, carbon-, and gold-based biomaterials, CaXs biomaterials can dissolve into nontoxic ions and participate in the normal metabolism of organisms. Thus, they offer safer clinical solutions for disease theranostics. This review focuses on the state-of-the-art progress in CaXs biomaterials, which covers from their categories, characteristics and preparation methods to their bioapplications including diagnosis, treatment, and theranostics. Moreover, the current trends and key problems as well as the future prospects and challenges of CaXs biomaterials are also discussed at the end.


Assuntos
Materiais Biocompatíveis/uso terapêutico , Carbonato de Cálcio , Compostos de Cálcio , Fluoreto de Cálcio , Fosfatos de Cálcio , Silicatos , Nanomedicina Teranóstica , Materiais Biocompatíveis/química , Carbonato de Cálcio/química , Carbonato de Cálcio/uso terapêutico , Compostos de Cálcio/química , Compostos de Cálcio/uso terapêutico , Fluoreto de Cálcio/química , Fluoreto de Cálcio/uso terapêutico , Fosfatos de Cálcio/química , Fosfatos de Cálcio/uso terapêutico , Humanos , Silicatos/química , Silicatos/uso terapêutico
5.
Chem Soc Rev ; 47(17): 6454-6472, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-30024579

RESUMO

Glucose oxidase (GOx) is an endogenous oxido-reductase that is widely distributed in living organisms. Over recent years, GOx has attracted increasing interest in the biomedical field due to its inherent biocompatibility, non-toxicity, and unique catalysis against ß-d-glucose. GOx efficiently catalyzes the oxidization of glucose into gluconic acid and hydrogen peroxide (H2O2), which can be employed by various biosensors for the detection of cancer biomarkers. Various cancer therapeutic strategies have also been developed based on the catalytic chemistry of GOx: (1) the consumption of glucose provides an alternative strategy for cancer-starvation therapy; (2) the consumption of oxygen increases tumor hypoxia, which can be harnessed for hypoxia-activated therapy; (3) the generation of gluconic acid enhances the acidity of the tumor microenvironment, which can trigger pH-responsive drug release; (4) the generation of H2O2 increases the levels of tumor oxidative stress, and the H2O2 can be converted into toxic hydroxyl radicals that can kill cancer cells upon exposure to light irradiation or via the Fenton reaction. More importantly, GOx can be combined with other enzymes, hypoxia-activated prodrugs, photosensitizers or Fenton's reagents, to generate multi-modal synergistic cancer therapies based on cancer starvation therapy, hypoxia-activated therapy, oxidation therapy, photodynamic therapy, and/or photothermal therapy. Such multi-modal approaches are anticipated to exert a stronger therapeutic effect than one therapeutic mode alone. Thus, maximizing the potential of GOx in a biomedical context will offer novel clinical solutions to diagnose and treat cancer. In this tutorial review, we introduce the recent advances of GOx in cancer diagnosis and treatment. We then emphasize the design principles and biomedical applications of GOx-based biosensors and cancer therapeutic approaches. Finally, we discuss the challenges and future prospects of GOx-based catalytic systems in biomedicine.


Assuntos
Técnicas Biossensoriais/métodos , Fungos/enzimologia , Glucose Oxidase/metabolismo , Neoplasias/diagnóstico , Neoplasias/terapia , Animais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Fungos/metabolismo , Glucose/análise , Glucose/metabolismo , Glucose Oxidase/uso terapêutico , Humanos , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo
6.
Acta Biomater ; 162: 44-56, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36934891

RESUMO

Chemodynamic therapy (CDT) is a powerful cancer treatment strategy by producing excessive amount of reactive oxygen species (ROS) to kill cancer cells. However, the inadequate hydrogen peroxide (H2O2) supply and antioxidant defense systems in tumor tissue significantly impair the therapeutic effect of CDT, hindering its further applications. Herein, we present an intelligent nanoplatform with H2O2 homeostasis disruption and oxidative stress amplification properties for enhanced CDT. This nanoplatform is obtained by encapsulating glucose oxidase (GOx) in a pH- and glutathione (GSH)-responsive degradable copper doped-zeolitic imidazolate framework (Cu-ZIF8), followed by loading of 3-amino-1,2,4-triazole (3AT) and modification of hyaluronic acid (HA) for tumor targeting delivery. The GOx@Cu-ZIF8-3AT@HA not only reduces energy supply and increases H2O2 level by exhausting intratumoral glucose, but also disturbs tumor antioxidant defense systems by inhibiting the activity of catalase (CAT) and depleting intracellular GSH, resulting in disrupted H2O2 homeostasis in tumor. Moreover, the elevated H2O2 will transform into highly toxic hydroxyl radical (·OH) by Cu+ that generated from redox reaction between Cu2+ and GSH, amplifying the oxidative stress to enhance the CDT efficacy. Consequently, GOx@Cu-ZIF8-3AT@HA has significantly inhibited the 4T1 xenograft tumor growth without discernible side effects, which provides a promising strategy for cancer management. STATEMENT OF SIGNIFICANCE: The inadequate H2O2 level and antioxidant defense system in tumor tissues significantly impair the therapeutic effect of CDT. Herein, we developed an intelligent nanoplatform with H2O2 homeostasis disruption and oxidative stress amplification properties for enhanced CDT. In this nanoplatform, GOx could exhaust intratumoral glucose to reduce energy supply accompanied with production of H2O2, while the suppression of CAT activity by 3AT and depletion of GSH by Cu2+ would weaken the antioxidant defense system of tumors. Ultimately, the raised H2O2 level would convert to highly toxic •OH by Fenton-like reaction, amplifying the CDT efficacy. This work provides a promising strategy for cancer management.


Assuntos
Antioxidantes , Neoplasias , Humanos , Antioxidantes/farmacologia , Peróxido de Hidrogênio , Biomimética , Estresse Oxidativo , Glutationa , Glucose , Glucose Oxidase , Homeostase , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral
7.
Polymers (Basel) ; 15(8)2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-37112014

RESUMO

The fabrication of pH-sensitive lignin-based materials has received considerable attention in various fields, such as biomass refining, pharmaceuticals, and detecting techniques. However, the pH-sensitive mechanism of these materials is usually depending on the hydroxyl or carboxyl content in the lignin structure, which hinders the further development of these smart materials. Here, a pH-sensitive lignin-based polymer with a novel pH-sensitive mechanism was constructed by establishing ester bonds between lignin and the active molecular 8-hydroxyquinoline (8HQ). The structure of the produced pH-sensitive lignin-based polymer was comprehensively characterized. The substituted degree of 8HQ was tested up to 46.6% sensitivity, and the sustained release performance of 8HQ was confirmed by the dialysis method, the sensitivity of which was found to be 60 times slower compared with the physical mixed sample. Moreover, the obtained pH-sensitive lignin-based polymer showed an excellent pH sensitivity, and the released amount of 8HQ under an alkaline condition (pH = 8) was obviously higher than that under an acidic condition (pH = 3 and 5). This work provides a new paradigm for the high-value utilization of lignin and a theory guidance for the fabrication of novel pH-sensitive lignin-based polymers.

8.
Exploration (Beijing) ; 3(6): 20210110, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38264686

RESUMO

In recent years, glucose oxidase (GOx) has aroused great research interest in the treatment of diseases related to abnormal glucose metabolisms like cancer and diabetes. However, as a kind of endogenous oxido-reductase, GOx suffers from poor stability and system toxicity in vivo. In order to overcome this bottleneck, GOx is encapsulated in calcium-based biomaterials (CaXs) such as calcium phosphate (CaP) and calcium carbonate (CaCO3) by using it as a biotemplate to simulate the natural biomineralization process. The biomineralized GOx holds improved stability and reduced side effects, due to the excellent bioactivity, biocompatibitliy, and biodegradability of CaXs. In this review, the state-of-the-art studies on GOx-mineralized CaXs are introduced with an emphasis on their application in various biomedical fields including disease diagnosis, cancer treatment, and diabetes management. The current challenges and future perspectives of GOx-mineralized CaXs are discussed, which is expected to promote further studies on these smart GOx-mineralized CaXs biomaterials for practical applications.

9.
Carbohydr Polym ; 90(1): 309-15, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24751046

RESUMO

The purposes of this study were to explore the influences of different cellulose types on the cellulose/CaCO3 composites, which were synthesized via the microwave-assisted method by using alkali extraction cellulose and microcrystalline cellulose, respectively. Experimental results demonstrated that the types of cellulose played an important role in the microstructure and morphologies of the cellulose/CaCO3 composites. The composites consisted of cellulose and pure phase CaCO3 (calcite). The sample synthesized using microcrystalline cellulose had better crystallinity than that of the sample using alkali extraction cellulose. The cellulose fibers and CaCO3 particles were observed using alkali extraction cellulose. However, using microcrystalline cellulose instead of alkali extraction cellulose, the cellulose with irregular shape and CaCO3 microspheres were obtained. Therefore, choosing appropriate cellulose types is very important for the formation of cellulose/CaCO3 composites. Furthermore, the Raman spectra of the cellulose/CaCO3 composites were also researched.

10.
ACS Nano ; 16(10): 17298-17312, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36166667

RESUMO

Photodynamic therapy (PDT) has attained extensive attention as a noninvasive tumor treatment modality. However, the hypoxia in solid tumors, skin phototoxicity of "always on" photosensitizers (PSs), and abundant supply of glutathione (GSH) in cancer cells severely hampered the clinical applications of PDT. Herein, a self-oxygenation nanoplatform (denoted as CZCH) with GSH depletion ability was encapsulated into the hyaluronic acid microneedle patch (MN-CZCH) to simultaneously improve the biosafety and therapeutic efficacy of PDT. The Cu2+-doped porous zeolitic imidazolate framework incorporated with catalase (CAT) is capable of efficiently loading PS 2-(1-hexyloxyethyl)-2-divinylpyropheophorbic-a (HPPH). The CZCH intermingled MN patch (MN-CZCH) could effectively penetrate the stratum corneum, topically transport HPPH to the target tumor site, achieve a long tumor retention time, and enhance the efficacy of PDT via the simultaneously synergistic effect of CAT-catalyzed self-supplying O2 and Cu2+-mediated GSH depletion. Using traceable fluorescence (FL) imaging of the released HPPH from CZCH, the FL imaging-guided repeatable PDT can be achieved for enhanced antitumor efficacy. As a result, the MN-CZCH patch exhibited excellent therapeutic efficacy against melanoma with minimal toxicity, which has promising potential for cancer theranostics.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Catalase/uso terapêutico , Ácido Hialurônico/uso terapêutico , Glutationa , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
11.
Nat Commun ; 13(1): 6238, 2022 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266306

RESUMO

5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca2+/Cu2+-interferences-enhanced repeatable photodynamic therapy, making this theranostic patch promising for clinical practice.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Ácido Aminolevulínico/farmacologia , Catalase/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fármacos Fotossensibilizantes , Ferroquelatase/metabolismo , Biologia Sintética , Cobre/metabolismo , Protoporfirinas/metabolismo , Neoplasias/tratamento farmacológico , Oxigênio/metabolismo , Ligases/metabolismo , Linhagem Celular Tumoral
12.
Adv Sci (Weinh) ; 9(12): e2102220, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35218328

RESUMO

Intrauterine adhesions (IUAs) caused by mechanical damage or infection increase the risk of infertility in women. Although numerous physical barriers such as balloon or hydrogel are developed for the prevention of IUAs, the therapeutic efficacy is barely satisfactory due to limited endometrial healing, which may lead to recurrence. Herein, a second near-infrared (NIR-II) light-responsive shape memory composite based on the combination of cuprorivaite (CaCuSi4 O10 ) nanosheets (CUP NSs) as photothermal conversion agents and polymer poly(d,l-lactide-co-trimethylene carbonate) (PT) as shape memory building blocks is developed. The as-prepared CUP/PT composite possesses excellent shape memory performance under NIR-II light, and the improved operational feasibility as an antiadhesion barrier for the treatment of IUAs. Moreover, the released ions (Cu, Si) can stimulate the endometrial regeneration due to the angiogenic bioactivity. This study provides a new strategy to prevent IUA and restore the injured endometrium relied on shape memory composite with enhanced tissues reconstruction ability.


Assuntos
Endométrio , Doenças Uterinas , Cobre , Endométrio/patologia , Feminino , Humanos , Regeneração , Silicatos/uso terapêutico , Aderências Teciduais/tratamento farmacológico , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controle , Doenças Uterinas/tratamento farmacológico , Doenças Uterinas/patologia , Doenças Uterinas/prevenção & controle
13.
Adv Mater ; 34(5): e2103980, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34775641

RESUMO

Complete resection of isocitrate dehydrogenase 1 (IDH1) (R132H) glioma is unfeasible and the classic post-surgical chemo/radiotherapy suffers from high recurrence and low survival rate. IDH1 (R132H) cells are sensitive to low concentrations of glucose and high concentrations of reactive oxygen species (ROS) due to inherent metabolism reprograming. Hence, a starvation/chemodynamic therapeutic gel is developed to combat residual IDH1 (R132H) tumor cells after surgery. Briefly, glucose oxidase (GOx) is mineralized with manganese-doped calcium phosphate to form GOx@MnCaP nanoparticles, which are encapsulated into the fibrin gel (GOx@MnCaP@fibrin). After spraying gel in the surgical cavity, GOx catalyzes the oxidation of glucose in residual IDH1 (R132H) cells and produces H2 O2 . The generated H2 O2 is further converted into highly lethal hydroxyl radicals (•OH) by a Mn2+ -mediated Fenton-like reaction to further kill the residual IDH1 (R132H) cells. The as-prepared starvation/chemodynamic therapeutic gel shows much higher therapeutic efficacy toward IDH1 (R132H) cells than IDH1 (WT) cells, and achieves long-term survival.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/tratamento farmacológico , Glioma/patologia , Humanos , Isocitrato Desidrogenase/metabolismo , Isocitrato Desidrogenase/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
14.
Adv Mater ; 33(48): e2103978, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34580926

RESUMO

Photodynamic therapy (PDT) has aroused great research interest in recent years owing to its high spatiotemporal selectivity, minimal invasiveness, and low systemic toxicity. However, due to the hypoxic nature characteristic of many solid tumors, PDT is frequently limited in therapeutic effect. Moreover, the consumption of O2 during PDT may further aggravate the tumor hypoxic condition, which promotes tumor proliferation, metastasis, and invasion resulting in poor prognosis of treatment. Therefore, numerous efforts have been made to increase the O2 content in tumor with the goal of enhancing PDT efficacy. Herein, these strategies developed in past decade are comprehensively reviewed to alleviate tumor hypoxia, including 1) delivering exogenous O2 to tumor directly, 2) generating O2 in situ, 3) reducing tumor cellular O2 consumption by inhibiting respiration, 4) regulating the TME, (e.g., normalizing tumor vasculature or disrupting tumor extracellular matrix), and 5) inhibiting the hypoxia-inducible factor 1 (HIF-1) signaling pathway to relieve tumor hypoxia. Additionally, the O2 -independent Type-I PDT is also discussed as an alternative strategy. By reviewing recent progress, it is hoped that this review will provide innovative perspectives in new nanomaterials designed to combat hypoxia and avoid the associated limitation of PDT.


Assuntos
Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Matriz Extracelular/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Oxigênio/química , Oxigênio/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Hipóxia Tumoral/efeitos dos fármacos , Microambiente Tumoral
15.
Bioact Mater ; 6(9): 2698-2710, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33665502

RESUMO

In recent years, metal peroxide (MO2) such as CaO2 has received more and more attention in cancer treatment. MO2 is readily decompose to release metal ions and hydrogen peroxide in the acidic tumor microenvironment (TME), resulting metal ions overloading, decreased acidity and elevated oxidative stress in TME. All of these changes making MO2 an excellent tumor therapeutic agent. Moreover, by combining MO2 with photosensitizers, enzymes or Fenton reagents, MO2 can assist and promote various tumor therapies such as photodynamic therapy and chemodynamic therapy. In this review, the synthesis and modification methods of MO2 are introduced, and the representative studies of MO2-based tumor monotherapy and combination therapy are discussed in detail. Finally, the current challenges and prospects of MO2 in the field of tumor therapy are emphasized to promote the development of MO2-based cancer treatment.

16.
ACS Nano ; 15(1): 1627-1639, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33356128

RESUMO

Multifunctional nanotheranostics are typically designed by integrating multiple functional components. This approach not only complicates the preparation process but also hinders any bioapplication due to the potential toxic effects when each component is metabolized. Here, we report a safe, biodegradable, and tumor-specific nanocarrier that, once activated by the acidic tumor microenvironment (TME), has diagnostic and therapeutic functions suitable for tumor theranostics. Our nanocarrier is composed of biomineralized manganese carbonate (BMC) nanoparticles (NPs) that readily decompose to release Mn2+ ions and CO2 gas in the acidic TME due to its intrinsic pH-dependent solubility. Mn2+ and CO2 release permits magnetic resonance and ultrasound imaging of tumors, respectively. These NPs can be loaded with the anticancer drug doxorubicin (DOX): BMC-DOX has high tumor inhibition effects both in vitro and in vivo due to combined Mn2+-mediated chemodynamic therapy and DOX-induced chemotherapy. This tumor-specific actuating nanocarrier might be a promising candidate for clinical translation.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Medicina de Precisão , Nanomedicina Teranóstica , Microambiente Tumoral
17.
Adv Mater ; 33(7): e2006892, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33394515

RESUMO

Chemodynamic therapy (CDT) is an emerging therapy method that kills cancer cells by converting intracellular hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (• OH). To overcome the current limitations of the insufficient endogenous H2 O2 and the high concentration of glutathione (GSH) in tumor cells, an intelligent nanocatalytic theranostics (denoted as PGC-DOX) that possesses both H2 O2 self-supply and GSH-elimination properties for efficient cancer therapy is presented. This nanoplatform is constructed by a facile one-step biomineralization method using poly(ethylene glycol)-modified glucose oxidase (GOx) as a template to form biodegradable copper-doped calcium phosphate nanoparticles, followed by the loading of doxorubicin (DOX). As an enzyme catalyst, GOx can effectively catalyze intracellular glucose to generate H2 O2 , which not only starves the tumor cells, but also supplies H2 O2 for subsequent Fenton-like reaction. Meanwhile, the redox reaction between the released Cu2+ ions and intracellular GSH will induce GSH depletion and reduce Cu2+ to Fenton agent Cu+ ions, and then trigger the H2 O2 to generate • OH by a Cu+ -mediated Fenton-like reaction, resulting in enhanced CDT efficacy. The integration of GOx-mediated starvation therapy, H2 O2 self-supply and GSH-elimination enhanced CDT, and DOX-induced chemotherapy, endow the PGC-DOX with effective tumor growth inhibition with minimal side effects in vivo.


Assuntos
Antineoplásicos/química , Doxorrubicina/química , Glutationa/química , Nanocápsulas/química , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/química , Animais , Antineoplásicos/farmacologia , Fosfatos de Cálcio/química , Catálise , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Terapia Combinada , Cobre/química , Doxorrubicina/farmacologia , Glucose Oxidase/metabolismo , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Radical Hidroxila/metabolismo , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias Experimentais , Imagem Óptica , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica
18.
Adv Healthc Mater ; 10(23): e2101563, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34632723

RESUMO

Gas therapy is an emerging "green" cancer treatment strategy; however, its outcome often restricted by the complexity, diversity, and heterogeneity of tumor. Herein, a tumor targeting and tumor microenvironment-activated calcium phosphate nanotheranostic system (denoted as GCAH) is constructed for effective synergistic cancer starvation/gas therapy. GCAH is obtained by a facile biomineralization strategy using glucose oxidase (GOx) as a biotemplate, followed by loading of l-Arginine (L-Arg) and modification of hyaluronic acid (HA) to allow special selectivity for glycoprotien CD44 overexpressed cancer cells. This nanotheranostic system not only exhausts the glucose nutrients in tumor region by the GOx-triggered glucose oxidation, the generated H2 O2 can oxidize L-Arg into NO under acidic tumor microenvironment for enhanced gas therapy. As such, there are significant enhancement effects of starvation therapy and gas therapy through the cascade reactions of GOx and L-Arg, which yields a remarkable synergistic therapeutic effect for 4T1 tumor-bearing mice without discernible toxic side effects.


Assuntos
Nanopartículas , Neoplasias , Animais , Fosfatos de Cálcio , Glucose Oxidase , Peróxido de Hidrogênio , Camundongos , Microambiente Tumoral
19.
J Mater Chem B ; 7(10): 1541-1562, 2019 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-32254901

RESUMO

In recent decades, cellulose has been extensively investigated due to its favourable properties, such as hydrophilicity, low-cost, biodegradability, biocompatibility, and non-toxicity, which makes it a good feedstock for the synthesis of biocompatible hydrogels. The plentiful hydrophilic functional groups (such as hydroxyl, carboxyl, and aldehyde groups) in the backbone of cellulose and its derivatives can be used to prepare hydrogels easily with fascinating structures and properties, leading to burgeoning research interest in biomedical applications. This review focuses on state-of-the-art progress in cellulose-based hydrogels, which covers from their preparation methods (including chemical methods and physical methods) and physicochemical properties (such as stimuli-responsive properties, mechanical properties, and self-healing properties) to their biomedical applications, including drug delivery, tissue engineering, wound dressing, bioimaging, wearable sensors and so on. Moreover, the current challenges and future prospects for cellulose-based hydrogels in regard to their biomedical applications are also discussed at the end.


Assuntos
Tecnologia Biomédica/métodos , Celulose/química , Sistemas de Liberação de Medicamentos/métodos , Hidrogéis/química , Humanos
20.
Mater Sci Eng C Mater Biol Appl ; 96: 426-435, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30606552

RESUMO

Vaterite is recognized as an important biomedical material owing to its features such as high specific surface area, high solubility, high dispersion, and small specific gravity. Herein, we report a facile and green sonochemical route to prepare vaterite nanospheres (assembled from rice-shaped nanoparticles) with average diameter of 206-246 nm by using cellulose as substrate. The important role of cellulose concentration on the phase of the products was systematically investigated, and the formation mechanism of vaterite was proposed. Moreover, the as-prepared cellulose/vaterite nanocomposites have a good cytocompatibility and a relatively high protein adsorption ability using hemoglobin as a model protein. These results indicate that the as-prepared cellulose/vaterite nanocomposites are promising for applications in biomedical fields, such as protein adsorption.


Assuntos
Carbonato de Cálcio/química , Celulose/química , Hemoglobinas/química , Nanocompostos/química , Nanosferas/química , Adsorção , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA