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1.
Nanoscale ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774090

RESUMO

This article describes the fabrication of hollow manganese/cobalt oxide nanoparticles (MCO NPs) with a tunable size through a redox reaction and the Kirkendall effect for cancer imaging and drug delivery. MCO-70 NPs (with an average size of 70 nm) can act as glutathione (GSH)-responsive contrast agents for dual T1/T2-weighted magnetic resonance imaging (MRI). The degradation of MCO NPs by GSH led to the enhancement of their T1 and T2 signals by 2.24- and 3.43-fold compared with those of MCO NPs before degradation, respectively. Antitumor agents such as doxorubicin (Dox) could be encapsulated inside the cavity of the hollow MCO NPs (MCO-70-Dox) and be released in the presence of GSH. The MCO-70-Dox NPs showed good tumor growth inhibition effects in vitro and in vivo, and can be promising drug delivery vehicles and MRI contrast agents for tumor diagnosis and reporting drug release.

2.
Theranostics ; 9(24): 7200-7209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695762

RESUMO

Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosystems that combine endogenous and exogenous ROS to enhance oxidative stress-mediated cancer cell death. Methods: A ROS-generating agent based on polymer-modified zinc peroxide nanoparticles (ZnO2 NPs) was presented, which simultaneously delivered exogenous H2O2 and Zn2+ capable of amplifying endogenous ROS production for synergistic cancer therapy. Results: After internalization into tumor cells, ZnO2 NPs underwent decomposition in response to mild acidic pH, resulting in controlled release of H2O2 and Zn2+. Intriguingly, Zn2+ could increase the production of mitochondrial O2·- and H2O2 by inhibiting the electron transport chain, and thus exerted anticancer effect in a synergistic manner with the exogenously released H2O2 to promote cancer cell killing. Furthermore, ZnO2 NPs were doped with manganese via cation exchange, making them an activatable magnetic resonance imaging contrast agent. Conclusion: This study establishes a ZnO2-based theranostic nanoplatform which achieves enhanced oxidative damage to cancer cells by a two-pronged approach of combining endogenous and exogenous ROS.

3.
J Chem Phys ; 151(4): 044201, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31370556

RESUMO

Signal Amplification By Reversible Exchange (SABRE) and its heteronuclear variant SABRE in SHield Enables Alignment Transfer to Heteronuclei create large nuclear magnetization in target ligands, exploiting level crossings in an iridium catalyst that transiently binds both the ligands and parahydrogen. This requires a specific, small magnetic field to match Zeeman splittings to scalar couplings. Here, we explore a different strategy, direct creation of heteronuclear singlet states in the target ligands, which produces enhanced signals at other field strengths, including zero field. We also show that pulsed methods (including pulsed field nulling) coherently and selectively pump such singlets, affording a significant enhancement on the resulting hyperpolarization.

4.
Chem Soc Rev ; 48(19): 5140-5176, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31464313

RESUMO

This review contributes towards a systematic understanding of the mechanism of shape-dependent effects on nanoparticles (NPs) for elaborating and predicting their properties and applications based on the past two decades of research. Recently, the significance of shape-dependent physical chemistry and biomedicine has drawn ever increasing attention. While there has been a great deal of effort to utilize NPs with different morphologies in these fields, so far research studies are largely localized in particular materials, synthetic methods, or biomedical applications, and have ignored the interactional and interdependent relationships of these areas. This review is a comprehensive description of the NP shapes from theory, synthesis, property to application. We figure out the roles that shape plays in the properties of different kinds of nanomaterials together with physicochemical and biomedical applications. Through systematic elaboration of these shape-dependent impacts, better utilization of nanomaterials with diverse morphologies would be realized and definite strategies would be expected for breakthroughs in these fields. In addition, we have proposed some critical challenges and open problems that need to be addressed in nanotechnology.


Assuntos
Nanoestruturas/química , Animais , Catálise , Humanos , Imagem por Ressonância Magnética , Microscopia Confocal , Nanoestruturas/uso terapêutico , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Análise Espectral Raman , Propriedades de Superfície
5.
Adv Mater ; 31(37): e1903443, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31379091

RESUMO

The targeted and sustained drug release from stimuli-responsive nanodelivery systems is limited by the irreversible and uncontrolled disruption of the currently used nanostructures. Bionic nanocapsules are designed by cross-linking polythymine and photoisomerized polyazobenzene (PETAzo) with adenine-modified ZnS (ZnS-A) nanoparticles (NPs) via nucleobase pairing. The ZnS-A NPs convert X-rays into UV radiation that isomerizes the azobenzene groups, which allows controlled diffusion of the active payloads across the bilayer membranes. In addition, the nucleobase pairing interactions between PETAzo and ZnS-A prevent drug leakage during their in vivo circulation, which not only enhances tumor accumulation but also maintains stability. These nanocapsules with tunable permeability show prolonged retention, remotely controlled drug release, enhanced targeted accumulation, and effective antitumor effects, indicating their potential as an anticancer drug delivery system.

6.
ACS Appl Mater Interfaces ; 11(31): 27558-27567, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31317730

RESUMO

Glutathione (GSH), one of the most significant reducing species in vivo, plays important roles in a variety of diseases and cellular functions. Precise quantification of GSH via advanced noninvasive photoacoustic imaging (PAI) is of vital significance for the early diagnosis and prompt treatment of GSH-related deep-seated diseases, which stresses the need for custom-design of GSH-sensitive PAI probes with changeable near-infrared spectroscopy (NIR) absorption. In this work, a novel intelligent tumor microenvironment-activated ratiometric PAI nanoprobe is first developed with the intention of specific ultrasensitive detection of intratumoral GSH by overcoming the limitations of previously reported fluorescent or PA imaging sensors. This special ratiometric PAI nanoprobe (CR-POM) is synthesized through the self-assembly of croconaine (CR) dye and molybdenum-based polyoxometalate (POM) clusters with opposite NIR absorbance change in response to GSH. The resulting amplified ratiometric absorbance (Ab866/Ab700), the relatively low limit of detection value (0.51 mM), and the unique acidity-activated self-aggregation contribute to the prolonged intratumoral retention and enhanced tumor accumulation of CR-POM for accurate quantification of intratumoral GSH (0.5-10 mM). Featuring the additional merit of 64Cu radiolabeling for whole-body positron-emission tomography imaging, the smartly designed CR-POM nanoprobe will open new horizons for real-time noninvasive monitoring of biodistribution and simultaneous accurate quantification of GSH levels, especially in tumor and other GSH-related pathophysiological processes.

7.
Biomaterials ; 218: 119365, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31344642

RESUMO

Metal-organic framework (MOF) nanoparticles have shown great potential as carrier platforms in theranostic applications. However, their poor physiological stability in phosphate-based media has limited their biological applications. Here, we studied the dissociation of MOF nanoparticles under physiological conditions, both in vitro and in vivo, and developed an in situ polymerization strategy on MOF nanoparticles for enhanced stability under physiological conditions and stimulus-responsive intracellular drug release. With polymer wrapped on the surface serving as a shield, the nanoscale MOFs were protected from decomposition by phosphate ions or acid and prevented the loaded cargos from leaking. An in vivo positron emission tomography (PET) study of 64Cu-labelled porphyrinic MOF indicated prolonged circulation time of the in situ polymerized MOF nanoparticles and greater tumor accumulation than unmodified MOF nanoparticles. With enhanced stability, cargos loaded into MOF nanoparticles or prodrugs conjugated on the surface can be efficiently delivered and released upon stimulus-responsive cleavage.

8.
Mol Cancer ; 18(1): 110, 2019 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-31228940

RESUMO

BACKGROUND: METTL3 is known to be involved in all stages in the life cycle of RNA. It affects the tumor formation by the regulation the m6A modification in the mRNAs of critical oncogenes or tumor suppressors. In bladder cancer, METTL3 could promote the bladder cancer progression via AFF4/NF-κB/MYC signaling network by an m6A dependent manner. Recently, METTL3 was also found to affect the m6A modification in non-coding RNAs including miRNAs, lincRNAs and circRNAs. However, whether this mechanism is related to the proliferation of tumors induced by METTL3 is not reported yet. METHODS: Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the expression of METTL3 in bladder cancer. The survival analysis was adopted to explore the association between METTL3 expression and the prognosis of bladder cancer. Bladder cancer cells were stably transfected with lentivirus and cell proliferation and cell cycle, as well as tumorigenesis in nude mice were performed to assess the effect of METTL3 in bladder cancer. RNA immunoprecipitation (RIP), co-immunoprecipitations and RNA m6A dot blot assays were conducted to confirm that METTL3 interacted with the microprocessor protein DGCR8 and modulated the pri-miR221/222 process in an m6A-dependent manner. Luciferase reporter assay was employed to identify the direct binding sites of miR221/222 with PTEN. Colony formation assay and CCK8 assays were conducted to confirm the function of miR-221/222 in METTL3-induced cell growth in bladder cancer. RESULTS: We confirmed the oncogenic role of METTL3 in bladder cancer by accelerating the maturation of pri-miR221/222, resulting in the reduction of PTEN, which ultimately leads to the proliferation of bladder cancer. Moreover, we found that METTL3 was significantly increased in bladder cancer and correlated with poor prognosis of bladder cancer patients. CONCLUSIONS: Our findings suggested that METTL3 may have an oncogenic role in bladder cancer through interacting with the microprocessor protein DGCR8 and positively modulating the pri-miR221/222 process in an m6A-dependent manner. To our knowledge, this is the first comprehensive study that METTL3 affected the tumor formation by the regulation the m6A modification in non-coding RNAs, which might provide fresh insights into bladder cancer therapy.

9.
Theranostics ; 9(10): 2791-2799, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244923

RESUMO

The design of hybrid metal-organic framework (MOF) nanomaterials by integrating inorganic nanoparticle into MOF (NP@MOF) has demonstrated outstanding potential for obtaining enhanced, collective, and extended novel physiochemical properties. However, the reverse structure of MOF-integrated inorganic nanoparticle (MOF@NP) with multifunction has rarely been reported. Methods: We developed a facile in-situ growth method to integrate MOF nanoparticle into inorganic nanomaterial and designed a fluorescence switch to trigger enhanced photodynamic therapy. The influence of "switch" on the photodynamic activity was studied in vitro. The in vivo mice with tumor model was applied to evaluate the "switch"-triggered enhanced photodynamic therapy efficacy. Results: A core-satellites structure with fluorescence off and on function was obtained when growing MnO2 on the surface of fluorescent zeolitic imidazolate framework (ZIF-8) nanoparticles. Furthermore, A core-shell structure with photodynamic activity off and on function was achieved by growing MnO2 on the surface of porphyrinic ZrMOF nanoparticles (ZrMOF@MnO2). Both the fluorescence and photodynamic activities can be turned off by MnO2 and turned on by GSH. The GSH-responsive activation of photodynamic activity of ZrMOF@MnO2 significantly depleted the intracellular GSH via a MnO2 reduction reaction, thus triggering an enhanced photodynamic therapy efficacy. Finally, the GSH-reduced Mn2+ provided a platform for magnetic resonance imaging-guided tumor therapy. Conclusion: This work highlights the impact of inorganic nanomaterial on the MOF properties and provides insight to the rational design of multifunctional MOF-inorganic nanomaterial complexes.

10.
J Am Chem Soc ; 141(25): 9937-9945, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31199131

RESUMO

Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H2O2 into hydroxyl radical (•OH), but endogenous H2O2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H2O2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2. The CP nanodots were prepared through coordination of H2O2 to Cu2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.

11.
Angew Chem Int Ed Engl ; 58(26): 8752-8756, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31046176

RESUMO

Tumor hypoxia, the "Achilles' heel" of current cancer therapies, is indispensable to drug resistance and poor therapeutic outcomes especially for radiotherapy. Here we propose an in situ catalytic oxygenation strategy in tumor using porphyrinic metal-organic framework (MOF)-gold nanoparticles (AuNPs) nanohybrid as a therapeutic platform to achieve O2 -evolving chemoradiotherapy. The AuNPs decorated on the surface of MOF effectively stabilize the nanocomposite and serve as radiosensitizers, whereas the MOF scaffold acts as a container to encapsulate chemotherapeutic drug doxorubicin. In vitro and in vivo studies verify that the catalase-like nanohybrid significantly enhances the radiotherapy effect, alleviating tumor hypoxia and achieving synergistic anticancer efficacy. This hybrid nanomaterial remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theranostic nanomedicines.

12.
J Am Chem Soc ; 141(20): 8158-8170, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31053030

RESUMO

In the present study, we report the development of magnetic-plasmonic bilayer vesicles assembled from iron oxide-gold Janus nanoparticles (Fe3O4-Au JNPs) for reactive oxygen species (ROS) enhanced chemotherapy. The amphiphilic Fe3O4-Au JNPs were grafted with poly(ethylene glycol) (PEG) on the Au surface and ROS-generating poly(lipid hydroperoxide) (PLHP) on the Fe3O4 surface, respectively, which were then assembled into vesicles containing two closely attached Fe3O4-Au NPs layers in opposite directions. The self-assembly mechanism of the bilayered vesicles was elucidated by performing a series of numerical simulations. The enhanced optical properties of the bilayered vesicles were verified by the calculated results and experimental data. The vesicles exhibited enhanced T2 relaxivity and photoacoustic properties over single JNPs due to the interparticle magnetic dipole interaction and plasmonic coupling. In particular, the vesicles are pH responsive and disassemble into single JNPs in the acidic tumor environment, activating an intracellular biochemical reaction between the grafted PLHP and released ferrous ions (Fe2+) from Fe3O4 NPs, resulting in highly efficient local ROS generation and increased intracellular oxidative stress. In combination with the release of doxorubicin (DOX), the vesicles combine ROS-mediated cytotoxicity and DOX-induced chemotherapy, leading to greatly improved therapeutic efficacy than monotherapies. High tumor accumulation efficiency and fast vesicle clearance from the body were also confirmed by positron emission tomography (PET) imaging of radioisotope 64Cu-labeled vesicles.

13.
Bioconjug Chem ; 30(6): 1821-1829, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31117347

RESUMO

Magnetic resonance imaging (MRI) diagnosis is better assisted by contrast agents that can augment the signal contrast in the imaging appearance. However, this technique is still limited by the inherently low sensitivity on the recorded signal changes in conventional T1 or T2 MRI in a qualitative manner. Here, we provide a new paradigm of MRI diagnosis using T1- T2 dual-modal MRI contrast agents for contrast-enhanced postimaging computations on T1 and T2 relaxation changes. An albumin-binding molecule (i.e., truncated Evans blue) chelated with paramagnetic manganese ion was developed as a novel T1- T2 dual-modal MRI contrast agent at high magnetic field (7 T). Furthermore, the postimaging computations on T1- T2 dual-modal MRI led to greatly enhanced signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) in both subcutaneous and orthotopic brain tumor models compared with traditional MRI methods. The T1- T2 dual-modal MRI computations have great potential to eliminate suspicious artifacts and false-positive signals in mouse brain imaging. This study may open new avenues for contrast-enhanced MRI diagnosis and holds great promise for precision medicine.

14.
J Exp Bot ; 70(18): 4849-4864, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30972421

RESUMO

It is predicted that high-temperature stress will increasingly affect crop yields worldwide as a result of climate change. In order to determine the genetic basis of thermotolerance of seed-set in maize under field conditions, we performed mapping of quantitative trait loci (QTLs) in a recombinant inbred line (RIL) population using a collection of 8329 specifically developed high-density single-nucleotide polymorphism (SNP) markers, combined with a genome-wide association study (GWAS) of 261 diverse maize lines using 259 973 SNPs. In total, four QTLs and 17 genes associated with 42 SNPs related to thermotolerance of seed-set were identified. Among them, four candidate genes were found in both linkage mapping and GWAS. Thermotolerance of seed-set was increased significantly in near-isogenic lines (NILs) that incorporated the four candidate genes in a susceptible parent background. The expression profiles of two of the four genes showed that they were induced by high temperatures in the maize tassel in a tolerant parent background. Our results indicate that thermotolerance of maize seed-set is regulated by multiple genes each of which has minor effects, with calcium signaling playing a central role. The genes identified may be exploited in breeding programs to improve seed-set and yield of maize under heat stress.

15.
Angew Chem Int Ed Engl ; 58(26): 8799-8803, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31034679

RESUMO

Single molecular nanoparticles (SMNPs) integrating imaging and therapeutic capabilities exhibit unparalleled advantages in cancer theranostics, ranging from excellent biocompatibility, high stability, prolonged blood lifetime to abundant tumor accumulation. Herein, we synthesize a sophisticated porphyrin nanocage that is further functionalized with twelve polyethylene glycol arms to prepare SMNPs (porSMNPs). The porphyrin nanocage embedded in porSMNPs can be utilized as a theranostic platform. PET imaging allows dynamic observation of the bio-distribution of porSMNPs, confirming their excellent circulation time and preferential accumulation at the tumor site, which is attributed to the enhanced permeability and retention effect. Moreover, the cage structure significantly promotes the photosensitizing effect of porSMNs by inhibiting the π-π stacking interactions of the photosensitizers, ablating of the tumors without relapse by taking advantage of photodynamic therapy.

16.
J Hazard Mater ; 375: 1-8, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31030075

RESUMO

Vanadium silicate (EVS) is a vanadium-substituted form of titanosilicate that has a high potential for use as a sorbent for mercury removal. In the present study, EVS with supported silver nanoparticles (EVS-Ag100) as the catalytic sorbent was synthesized for elemental mercury (Hg°) capture. The physical and chemical properties of the sorbents were investigated. The raw EVS exhibited a poor Hg° capture capacity (7.7 µg g-1), because most of the vanadium species in the structure of EVS were V4+. The loading of the silver could significantly enhance the Hg° capture capacity (63.4 µg g-1). EVS-Ag100 exhibited a superior Hg° capture performance at temperatures of approximately 150 °C. Silver nanoparticles that formed on the EVS were the active sites. In addition, the vanadium species of EVS-Ag100 exhibited higher Hg° oxidation activity than those in the framework of raw EVS. The XPS results revealed the activation of the vanadium species by the silver nanoparticles. After the capture of Hg° in the presence of O2, more V5+ was observed on the surface of EVS-Ag100. Exposure of EVS-Ag100 to a continuous simulated flue gas at 150 °C with a gas hourly space velocity of 220,000 h-1 led to Hg° removal efficiency of >96% in a 1 h test.

17.
Theranostics ; 9(5): 1358-1368, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30867836

RESUMO

It remains a major challenge to achieve precise on-demand drug release. Here, we developed a modular nanomedicine integrated with logic-gated system enabling programmable drug release for on-demand chemotherapy. Methods: We employed two different logical AND gates consisting of four interrelated moieties to construct the nanovesicles, denoted as v-A-CED2, containing oxidation-responsive nanovesicles (v), radical generators (A), and Edman linker conjugated prodrugs (CED2). The first AND logic gate is connected in parallel by mild hyperthermia ( I ) and acidic pH ( II ), which executes NIR laser triggered prodrug-to-drug transformation through Edman degradation. Meanwhile, the mild hyperthermia effect triggers alkyl radical generation ( III ) which contributes to internal oxidation and degradation of nanovesicles ( IV ). The second AND logic gate is therefore formed by the combination of I-IV to achieve programmable drug release by a single stimulus input NIR laser. The biodistribution of the nanovesicles was monitored by positron emission tomography (PET), photoacoustic, and fluorescence imaging. Results: The developed modular nanovesicles exhibited high tumor accumulation and effective anticancer effects both in vitro and in vivo. Conclusions: This study provides a novel paradigm of logic-gated programmable drug release system by a modular nanovesicle, which may shed light on innovation of anticancer agents and strategies.

18.
Small ; 15(16): e1900691, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30913380

RESUMO

Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.

19.
Nat Commun ; 10(1): 1241, 2019 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-30886142

RESUMO

The success of radiotherapy relies on tumor-specific delivery of radiosensitizers to attenuate hypoxia resistance. Here we report an ammonia-assisted hot water etching strategy for the generic synthesis of a library of small-sized (sub-50 nm) hollow mesoporous organosilica nanoparticles (HMONs) with mono, double, triple, and even quadruple framework hybridization of diverse organic moieties by changing only the introduced bissilylated organosilica precursors. The biodegradable thioether-hybridized HMONs are chosen for efficient co-delivery of tert-butyl hydroperoxide (TBHP) and iron pentacarbonyl (Fe(CO)5). Distinct from conventional RT, radiodynamic therapy (RDT) is developed by taking advantage of X-ray-activated peroxy bond cleavage within TBHP to generate •OH, which can further attack Fe(CO)5 to release CO molecules for gas therapy. Detailed in vitro and in vivo studies reveal the X-ray-activated cascaded release of •OH and CO molecules from TBHP/Fe(CO)5 co-loaded PEGylated HMONs without reliance on oxygen, which brings about remarkable destructive effects against both normoxic and hypoxic cancers.


Assuntos
Antineoplásicos/administração & dosagem , Quimiorradioterapia/métodos , Portadores de Fármacos/síntese química , Liberação Controlada de Fármacos/efeitos da radiação , Neoplasias/terapia , Animais , Monóxido de Carbono/química , Feminino , Células Hep G2 , Humanos , Radical Hidroxila/química , Radical Hidroxila/efeitos da radiação , Compostos de Ferro/administração & dosagem , Camundongos , Camundongos Nus , Nanopartículas/química , Compostos de Organossilício/síntese química , Tamanho da Partícula , Polietilenoglicóis/química , Porosidade , Células RAW 264.7 , Resultado do Tratamento , Raios X , Ensaios Antitumorais Modelo de Xenoenxerto , terc-Butil Hidroperóxido/administração & dosagem , terc-Butil Hidroperóxido/efeitos da radiação
20.
ACS Nano ; 13(3): 3083-3094, 2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30835435

RESUMO

A cancer vaccine is an important form of immunotherapy. Given their effectiveness for antigen processing and presentation, dendritic cells (DCs) have been exploited in the development of a therapeutic vaccine. Herein, a versatile polymersomal nanoformulation that enables generation of tumor-associated antigens (TAAs) and simultaneously serves as adjuvant for an in situ DC vaccine is reported. The chimeric cross-linked polymersome (CCPS) is acquired from self-assembly of a triblock copolymer, polyethylene glycol-poly(methyl methyacrylate- co-2-amino ethyl methacrylate (thiol/amine))-poly 2-(dimethylamino)ethyl methacrylate (PEG-P(MMA- co-AEMA (SH/NH2)-PDMA). CCPS can encapsulate low-dose doxorubicin hydrochloride (DOX) to induce immunogenic cell death (ICD) and 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH), a photosensitizer to facilitate photodynamic therapy (PDT) for reactive oxygen species (ROS) generation. This combination is able to enhance the population of TAAs and DC recruitment, eliciting an immune response cascade. In addition, CCPS with primary and tertiary amines act as adjuvant, both of which can stimulate DCs recruited to form an in situ DC vaccine after combination with TAAs for MC38 colorectal cancer treatment. In vivo results indicate that the all-in-one polymersomal nanoformulation (CCPS/HPPH/DOX) increases mature DCs in tumor-draining lymph nodes (tdLNs) and CD8+ T cells in tumor tissues to inhibit primary and distant MC38 tumor growth following a single intravenous injection with a low dose of DOX and HPPH.

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