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1.
Adv Mater ; 33(12): e2005062, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33565157

RESUMO

The rapid knowledge growth of nanomedicine and nanobiotechnology enables and promotes the emergence of distinctive disease-specific therapeutic modalities, among which nanomedicine-enabled/augmented nanodynamic therapy (NDT), as triggered by either exogenous or endogenous activators on nanosensitizers, can generate reactive radicals for accomplishing efficient disease nanotherapies with mitigated side effects and endowed disease specificity. As one of the most representative modalities of NDT, traditional light-activated photodynamics suffers from the critical and unsurmountable issues of the low tissue-penetration depth of light and the phototoxicity of the photosensitizers. To overcome these obstacles, versatile nanomedicine-enabled/augmented NDTs have been explored for satisfying varied biomedical applications, which strongly depend on the physicochemical properties of the involved nanomedicines and nanosensitizers. These distinctive NDTs refer to sonodynamic therapy (SDT), thermodynamic therapy (TDT), electrodynamic therapy (EDT), piezoelectric dynamic therapy (PZDT), pyroelectric dynamic therapy (PEDT), radiodynamic therapy (RDT), and chemodynamic therapy (CDT). Herein, the critical roles, functions, and biological effects of nanomedicine (e.g., sonosensitizing, photothermal-converting, electronic, piezoelectric, pyroelectric, radiation-sensitizing, and catalytic properties) for enabling the therapeutic procedure of NDTs, are highlighted and discussed, along with the underlying therapeutic principle and optimization strategy for augmenting disease-therapeutic efficacy and biosafety. The present challenges and critical issues on the clinical translations of NDTs are also discussed and clarified.

2.
Nat Commun ; 12(1): 218, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431882

RESUMO

Development of organic theranostic agents that are active in the second near-infrared (NIR-II, 1000-1700 nm) biowindow is of vital significance for treating deep-seated tumors. However, studies on organic NIR-II absorbing agents for photo-to-heat energy-converting theranostics are still rare simply because of tedious synthetic routes to construct extended π systems in the NIR-II region. Herein, we design a convenient strategy to engineer highly stable organic NIR-II absorbing theranostic nanoparticles (Nano-BFF) for effective phototheranostic applications via co-assembling first NIR (NIR-I, 650-1000 nm) absorbing boron difluoride formazanate (BFF) dye with a biocompatible polymer, endowing the Nano-BFF with remarkable theranostic performance in the NIR-II region. In vitro and in vivo investigations validate that Nano-BFF can serve as an efficient theranostic agent to achieve photoacoustic imaging guided deep-tissue photonic hyperthermia in the NIR-II biowindow, achieving dramatic inhibition toward orthotopic hepatocellular carcinoma. This work thus provides an insight into the exploration of versatile organic NIR-II absorbing nanoparticles toward future practical applications.


Assuntos
Temperatura Alta , Raios Infravermelhos , Luz , Compostos Orgânicos/química , Nanomedicina Teranóstica , Animais , Linhagem Celular Tumoral , Formazans/administração & dosagem , Formazans/farmacocinética , Camundongos Endogâmicos C57BL , Neoplasias/patologia , Neoplasias/terapia , Técnicas Fotoacústicas
3.
Artigo em Inglês | MEDLINE | ID: mdl-32808464

RESUMO

Energy-converting biomaterials (ECBs)-mediated cancer-therapeutic modalities have been extensively explored, which have achieved remarkable benefits to overwhelm the obstacles of traditional cancer-treatment modalities. Energy-driven cancer-therapeutic modalities feature their distinctive merits, including noninvasiveness, low mammalian toxicity, adequate therapeutic outcome, and optimistical synergistic therapeutics. In this advanced review, the prevailing mainstream ECBs can be divided into two sections: Reactive oxygen species (ROS)-associated energy-converting biomaterials (ROS-ECBs) and hyperthermia-related energy-converting biomaterials (H-ECBs). On the one hand, ROS-ECBs can transfer exogenous or endogenous energy (such as light, radiation, ultrasound, or chemical) to generate and release highly toxic ROS for inducing tumor cell apoptosis/necrosis, including photo-driven ROS-ECBs for photodynamic therapy, radiation-driven ROS-ECBs for radiotherapy, ultrasound-driven ROS-ECBs for sonodynamic therapy, and chemical-driven ROS-ECBs for chemodynamic therapy. On the other hand, H-ECBs could translate the external energy (such as light and magnetic) into heat for killing tumor cells, including photo-converted H-ECBs for photothermal therapy and magnetic-converted H-ECBs for magnetic hyperthermia therapy. Additionally, the biosafety issues of ECBs are expounded preliminarily, guaranteeing the ever-stringent requirements of clinical translation. Finally, we discussed the prospects and facing challenges for constructing the new-generation ECBs for establishing intriguing energy-driven cancer-therapeutic modalities. This article is categorized under: Nanotechnology Approaches to Biology >Nanoscale Systems in Biology.

4.
Adv Sci (Weinh) ; 7(21): 2001549, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33173728

RESUMO

As an essential trace element in the human body, transitional metal copper (Cu) ions are the bioactive components within the body featuring dedicated biological effects such as promoting angiogenesis and influencing lipid/glucose metabolism. The recent substantial advances of nanotechnology and nanomedicine promote the emerging of distinctive Cu-involved biomaterial nanoplatforms with intriguing theranostic performances in biomedicine, which are originated from the biological effects of Cu species and the physiochemical attributes of Cu-composed nanoparticles. Based on the very-recent significant progresses of Cu-involved nanotheranostics, this work highlights and discusses the principles, progresses, and prospects on the elaborate design and rational construction of Cu-composed functional nanoplatforms for a diverse array of biomedical applications, including photonic nanomedicine, catalytic nanotherapeutics, antibacteria, accelerated tissue regeneration, and bioimaging. The engineering of Cu-based nanocomposites for synergistic nanotherapeutics is also exemplified, followed by revealing their intrinsic biological effects and biosafety for revolutionizing their clinical translation. Finally, the underlying critical concerns, unresolved hurdles, and future prospects on their clinical uses are analyzed and an outlook is provided. By entering the "Copper Age," these Cu-involved nanotherapeutic modalities are expected to find more broad biomedical applications in preclinical and clinical phases, despite the current research and developments still being in infancy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32754578

RESUMO

Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and cartilage/bone destruction, which results in a high disability rate on human health and a huge burden on social economy. At present, traditional therapies based on drug therapy still cannot cure RA, in accompany with the potential serious side effects. Based on the development of nanobiotechnology and nanomedicine, energy conversion-based nanotherapy has demonstrated distinctive potential and performance in RA treatment. This strategy employs specific nanoparticles with intrinsic physiochemical properties to target lesions with the following activation by diverse external stimuli, such as light, ultrasound, microwave, and radiation. These nanoagents subsequently produce therapeutic effects or release therapeutic factors to promote necrotic apoptosis of RA inflammatory cells, reduce the concentration of related inflammatory factors, relieve the symptoms of RA, which are expected to ultimately improve the life quality of RA patients. This review highlights and discusses the versatile biomedical applications of energy conversion-based nanotherapy in efficient RA treatment, in together with the deep clarification of the facing challenges and further prospects on the final clinical translations of these energy conversion-based nanotherapies against RA.

6.
ACS Appl Mater Interfaces ; 12(38): 42558-42566, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32830482

RESUMO

With the fast development of nanomedicine, the imaging-guided and photo-induced cancer monotherapies can efficiently eliminate tumor lesions, which are strongly dependent on the construction of versatile theranostic nanoplatforms. Among diverse photo-converting nanoplatforms, silver chalcogenide nanoparticles feature high biocompatibility, narrow band gaps, and tunable optical properties, yet Ag2Te-based nanosystems are still at a proof-of-concept stage, and the exploration of Ag2Te-based nanosystems suitable for photonic tumor hyperthermia is challenging. Herein, we report on the construction of versatile ultrasmall Ag2Te quantum dots (QDs) via a facile biomineralization strategy. Especially, these Ag2Te QDs with negligible toxicity and excellent biocompatibility were developed for X-ray computed tomography (CT) imaging-guided photonic tumor hyperthermia by near-infrared (NIR) activation. The fabricated Ag2Te QDs exhibited a high tumor suppression rate (94.3%) on 4T1 breast tumor animal models due to the high photothermal-conversion efficiency (50.5%). Mechanistically, Ag2Te QDs were promising potential CT imaging agents for imaging guidance and monitoring during photonic hyperthermia. Importantly, Ag2Te QDs were rapidly eliminated from the body via feces and urine because of their ultrasmall sizes. This work not only broadens the biomedical applications of silver chalcogenide-based theranostic nanosystems but also provides the paradigm of theranostic nanosystems with a photonic tumor hyperthermia effect and outstanding contrast enhancement of high-performance CT imaging.

7.
Adv Mater ; 32(36): e2002246, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705751

RESUMO

The oxidation of intracellular biomolecules by reactive oxygen species (ROS) forms the basis for ROS-based tumor therapy. However, the current therapeutic modalities cannot catalyze H2 O2 and O2 concurrently for ROS generation, thereby leading to unsatisfactory therapeutic efficacy. Herein, it is reported a bioinspired hollow N-doped carbon sphere doped with a single-atom copper species (Cu-HNCS) that can directly catalyze the decomposition of both oxygen and hydrogen peroxide to ROS, namely superoxide ion (O2 •- ) and the hydroxyl radical (•OH), respectively, in an acidic tumor microenvironment for the oxidation of intracellular biomolecules without external energy input, thus resulting in an enhanced tumor growth inhibitory effect. Notably, the Fenton reaction turnover frequency of Cu species in Cu-HNCS is ≈5000 times higher than that of Fe in commercial Fe3 O4 nanoparticles. Experimental results and density functional theory calculations reveal that the high catalytic activity of Cu-HNCS originates from the single-atom copper, and the calculation predicts a next-generation Fenton catalyst. This work provides an effective paradigm of tumor parallel catalytic therapy for considerably enhanced therapeutic efficacy.

8.
Biomaterials ; 255: 120181, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32569864

RESUMO

Breast cancer (BC) is the most common malignant disease affecting women's health worldwide. The benefits from conventional therapeutic modalities are severely limited. An increasing number of promising photothermal materials have been recently developed and introduced into the therapeutic regimens of BC, but the underlying biological mechanism remains unclear. Silicon-based materials have enjoyed many popularities in the biomedical field owing to their desirable biocompatibility, biodegradability and versatility. Herein, we introduced two dimensional (2D) silicene nanosheets (SNSs) into the BC treatment and achieved profound photothermal-ablation efficacy. Importantly, this work reveals the underlying biological mechanism and regulation factors of photonic hyperthermia in BC. The RNA sequencing and immunoblot demonstrated that photothermia enhanced apoptosis in BC by activating caspase 3 and caspase 7. Importantly, knockdown of lysine demethylase KDM3A sensitized BC to photothermia epigenetically. It has been revealed that KDM3A could erase p53K372me1 and suppress the anti-cancer functions of p53, leading to the downregulation of pro-apoptotic proteins-PUMA and NOXA verified by Co-IP and ChIP-qPCR assays. Therefore, our results not only import near infrared light (NIR) induced photothermal ablation generated by SNSs-BSA into the BC treatment, but also clarify the underlying mechanism and regulation factors for further photothermal performance optimization and clinical translation.

9.
Biomaterials ; 256: 120206, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32599359

RESUMO

Silicene as an emerging two-dimensional material (2DM) spurs the broad research interests due to its prominent electronic and physical properties, however, still lacking in exploitation for the biological and medical practices. Herein, we constructed a 2D silicene-based theranostic nanoplatform, MnOx@silicene-BSA (MS-BSA), with tumor microenvironment (TME)-responsive and synergistic hyperthermia-augmented catalytic activity when irradiated by near infrared-II (NIR-II) laser because of the high photothermal-conversion efficiency of 2D silicene matrix. Such MS-BSA nanosheets possess the capability to react with glutathione (GSH) to generate Mn2+ and glutathione disulfide (GSSG) under acidity/reducing TME condition. With the presence/assistance of HCO3-, the released Mn2+ exhibited sensitive catalytic activity towards endogenous H2O2via Fenton-like reaction, enabling the generation of highly toxic hydroxyl radicals (•OH), which finally led to the enhanced nanocatalytic therapeutic efficacy followed by exogenous NIR-II laser exposure, originating from hyperthermia-augmented catalytic activity. Especially, these MS-BSA nanosheets accumulated into the tumor region to enable superb contrast enhancement of TME-responsive T1-weighted magnetic resonance imaging (MRI) and photoacoustic imaging (PAI), and high-efficient in vivo synergistic tumor eradication. Therefore, such an intelligent photothermal-enhanced catalytic theranostic nanoplatform could realize the exogenous/endogenous-responsive and cooperative hyperthermia-augmented tumor treatment and accurate tumor positioning/monitoring.

10.
Adv Mater ; 32(17): e2000542, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32162734

RESUMO

In situ toxification of less toxic substance for the generation of effective anticarcinogens at the specific tumor tissue has been a novel paradigm for combating cancer. Significant efforts have been recently dedicated to turning clinical-approved drugs into anticancer agents in specific tumor microenvironment by chemical reactions. Herein, a hollow mesoporous Prussian blue (HMPB)-based therapeutic nanoplatform, denoted as DSF@PVP/Cu-HMPB, is constructed by encapsulating alcohol-abuse drug disulfiram (DSF) into the copper-enriched and polyvinylpyrrolidone (PVP)-decorated HMPB nanoparticles to achieve in situ chemical reaction-activated and hyperthermia-amplified chemotherapy of DSF. Upon tumor accumulation of DSF@PVP/Cu-HMPB, the endogenous mild acidity in tumor condition triggers the biodegradation of the HMPB nanoparticle and the concurrent co-releases of DSF and Cu2+ , thus forming cytotoxic bis(N,N-diethyl dithiocarbamato)copper(II) complexes (CuL2 ) via DSF-Cu2+ chelating reaction. Moreover, by the intrinsic photothermal-conversion effect of PVP/Cu-HMPBs, the anticancer effect of DSF is augmented by the hyperthermia generated upon near-infrared irradiation, thus inducing remarkable cell apoptosis in vitro and tumor elimination in vivo on both subcutaneous and orthotopic tumor-bearing models. This strategy of in situ drug transition by chemical chelation reaction and photothermal-augmentation provides a promising paradigm for designing novel cancer-therapeutic nanoplatforms.

11.
Nanoscale Horiz ; 5(5): 857-868, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32100765

RESUMO

Photothermal therapy (PTT) is an emerging technology as a noninvasive therapeutic modality for inducing photonic cancer hyperthermia. However, current photothermal conversion agents suffer from low therapeutic efficiency and single functionality. Engineering crystal defects on the surface or substrate of semiconductors can substantially enhance their optical absorption capability as well as improve their photothermal effects in theranostic nanomedicines. In this study, a specific defect engineering strategy was developed to endow two-dimensional (2D) BiOCl nanosheets with intriguing photothermal conversion performance by creating oxygen vacancies on the surface (O-BiOCl). Importantly, the photothermal performance and photoacoustic imaging capability of the 2D O-BiOCl nanosheets could be precisely controlled by modulating the amounts of oxygen vacancies. The strong Bi-based X-ray attenuation coefficient endowed these nanosheets with the contrast-enhanced computed tomography imaging capability. The high near-infrared-triggered photonic hyperthermia for tumor ablation was systematically demonstrated both in vitro at the cellular level and in vivo for tumor breast cancer mice xenograft models. Based on the demonstrated high biocompatibility of these 2D O-BiOCl nanosheets, this work not only formulates an intriguing 2D photothermal nanoagent for tumor ablation, but also provides an efficient strategy to control the photothermal performance of nanoagents by defect engineering.

12.
Nanoscale ; 12(9): 5587-5600, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32100776

RESUMO

As one of the most promising noninvasive therapeutic modalities, sonodynamic therapy (SDT) can focus the ultrasound energy on tumor sites located in deep tissue and locally activate the preloaded sonosensitizer to kill tumor cells. However, exploring sonosensitizers with high SDT efficacy and desirable biosafety is still a significant challenge. Herein, we utilized the hydrophilic-hydrophobic self-assembly technology to assemble the hydrophobic organic dye Ce6 and broad spectral anti-cancer agent Paclitaxel with hydrophilic organic dye IR783 to generate a nanoscale sonosensitizer, Ce6-PTX@IR783, without the introduction of extra nanomaterials into the fabrication to guarantee high therapeutic biosafety and further potential clinical translation. The constructed nanodrug was endowed with an external ultrasound-activatable chemo-sonodynamic effect and photoacoustic imaging performance via integrating multiple moieties into one nanosystem. Ce6 could enhance the sonodynamic effect, while PTX exerted a chemotherapeutic effect, and IR783 was applied to increase tumor-specific accumulation and assist in fulfilling photoacoustic imaging. In particular, the small particle size (70 nm) of Ce6-PTX@IR783 contributed to the increased tumor accumulation via the enhanced permeability and retention effect. The high synergistically chemo-sonodynamic therapeutic efficacy has been successfully demonstrated in vitro and in vivo, in addition to the demonstrated high biodegradability, biocompatibility and biosafety. This facile self-assembly procedure provides an intriguing strategy for highly efficient utilization of hydrophobic drugs and is liable to realize large-scale production and further clinical translation.


Assuntos
Antineoplásicos Fitogênicos/química , Nanopartículas/química , Paclitaxel/química , Porfirinas/química , Radiossensibilizantes/química , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Endocitose , Feminino , Corantes Fluorescentes/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Oxigênio Singlete/metabolismo , Distribuição Tecidual , Transplante Heterólogo
13.
J Mater Chem B ; 8(11): 2296-2306, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32100784

RESUMO

A precise delineation of the intracranial glioblastoma boundary is urgently required for pre-surgical operations, due to the tumor-inherent infiltrative character of a tumor and the difficulty to completely remove the tumor. Magnetic resonance (MR) imaging is the leading clinical diagnostic tool for brain tumors, where a safe MR contrast agent that targets cancer biomarkers is critical for non-invasive and accurate brain tumor detection. In this work, a multifunctional targeted nanoprobe composed of PEGylated ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), with surface conjugated Angiopep-2, was successfully constructed by a stepwise reaction. The nanoprobe efficiently crossed the blood-brain barrier (BBB), targeted the glioblastoma and then generated positive contrast enhancement for T1-weighted MR imaging. Angiopep-2 was herein selected as a targeting ligand to construct the dual-targeting nanoprobes for MR imaging of brain tumors, because it can specifically combine to the low-density lipoprotein receptor-related protein (LRP), which is overexpressed in both BBB and glioblastoma cells. The targeting capability and, in particular, the biocompatibility/excretion of these ANG-modified MRI nanoprobes were systematically evaluated not only at the intracellular level in vitro, but also on tumor xenografts in vivo. This first report on ANG-engineered USPIONs as T1-weighted positive MR contrast agents for intracranial targeted glioblastoma imaging, provides a promising application potential for these SPION-based ultrasmall nanoprobes, not only for efficient pre-operative tumor diagnosis, but also for the targeted surgical resection of intracranial glioblastomas.

14.
Adv Sci (Weinh) ; 7(2): 1901511, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31993282

RESUMO

The residual of malignant tumor cells and lack of bone-tissue integration are the two critical concerns of bone-tumor recurrence and surgical failure. In this work, the rational integration of 2D Ti3C2 MXene is reported with 3D-printing bioactive glass (BG) scaffolds for achieving concurrent bone-tumor killing by photonic hyperthermia and bone-tissue regeneration by bioactive scaffolds. The designed composite scaffolds take the unique feature of high photothermal conversion of integrated 2D Ti3C2 MXene for inducing bone-tumor ablation by near infrared-triggered photothermal hyperthermia, which has achieved the complete tumor eradication on in vivo bone-tumor xenografts. Importantly, the rational integration of 2D Ti3C2 MXene is demonstrated to efficiently accelerate the in vivo growth of newborn bone tissue of the composite BG scaffolds. The dual functionality of bone-tumor killing and bone-tissue regeneration makes these Ti3C2 MXene-integrated composite scaffolds highly promising for the treatment of bone tumors, which also substantially broadens the biomedical applications of 2D MXenes in tissue engineering, especially on the treatment of bone tumors.

15.
Biomaterials ; 230: 119581, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31718885

RESUMO

Surgical resection of the epileptogenic region is typically regarded to be practical and efficient for complete elimination of intractable seizures, which cannot be simply controlled by anti-epileptic drugs alone. To achieve a precision removal of the epileptogenic region and even a surgical cure, molecular imaging of epilepsy markers is highly essential for non-invasive accurate detection of the epileptogenic region. In this work, a peptide-targeted nanoprobe, based on ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), PA-USPIONs, was elaborately constructed to enable highly selective delivery and sensitive T1-weighted positive magnetic resonance (MR) imaging of the epileptogenic region. Especially, Pepstatin A (PA), a small peptide which can specifically target to P-glycoprotein (P-gp) overexpressed at the epileptogenic region in a kainic acid (KA)-induced mice model of seizures, was conjugated onto the surface of PEGylated USPIONs. It has been demonstrated that the as-constructed PA-USPIONs nanoprobes have favorable T1 contrast enhancement and high r1 relaxivity compared with the clinically used T1-MR contrast agent (Gd-DTPA) by systematic in vitro and vivo assessments. Importantly, the toxicity evaluation, especially to brains, was assessed by the histological as well as hematological examinations, demonstrating that the fabricated PA-USPIONs nanoprobes are featured with excellent biocompatibility, guaranteeing the further potential clinical application. This first report on the development of USPIONs as T1-weighted MR contrast agents for active targeting of the epileptogenic region holds the high potential for precise resection of the according lesion in order to achieve therapeutic, often curative purposes.

16.
Biomaterials ; 219: 119374, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31369897

RESUMO

Traditional cancer-therapeutic modalities such as chemotherapy suffer from the low therapeutic efficiency and severe side effects. The emerging nanocatalytic therapy could in-situ catalyze the endogenous substances into highly toxic species and then efficiently kill the cancer cells, but the lack of high-performance nanocatalysts hinders their broad clinical translation. In this work, we have successfully developed, for the first time, nanosized zero-valence crystalized iron nanoparticles for in-situ triggering nanocatalytic Fenton reaction within tumor microenvironment to produce large amounts of hydroxyl radicals and subsequently kill the cancer cells, which could be further synergistically enhanced by either photonic hyperthermia or magnetic hyperthermia as assisted by these iron nanoparticles acting as photothermal-conversion or magnetothermal-conversion nanoagents, respectively. Especially, the excellent magnetic performance of these zero-valence crystallized iron nanoparticles has achieved both in vitro and in vivo contrast-enhance magnetic resonance imaging for potentially guiding the photonic/magnetic hyperthermia-synergistic nanocatalytic cancer therapy. This work not only provides the new type of iron-based nanoparticles for biomedical application, but also demonstrates the high efficiency of nanocatalytic cancer therapy as assisted by both photonic and magnetic hyperthermia.


Assuntos
Hipertermia Induzida , Ferro/química , Fenômenos Magnéticos , Nanopartículas/química , Neoplasias/terapia , Fótons , Animais , Materiais Biocompatíveis/química , Catálise , Linhagem Celular Tumoral , Meios de Contraste/química , Feminino , Humanos , Peróxido de Hidrogênio/química , Imagem por Ressonância Magnética , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Fototerapia , Povidona/química , Espécies Reativas de Oxigênio/metabolismo
17.
Adv Mater ; 31(37): e1903013, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347215

RESUMO

Silicon-based biomaterials play an indispensable role in biomedical engineering; however, due to the lack of intrinsic functionalities of silicon, the applications of silicon-based nanomaterials are largely limited to only serving as carriers for drug delivery systems. Meanwhile, the intrinsically poor biodegradation nature for silicon-based biomaterials as typical inorganic materials also impedes their further in vivo biomedical use and clinical translation. Herein, by the rational design and wet chemical exfoliation synthesis of the 2D silicene nanosheets, traditional 0D nanoparticulate nanosystems are transformed into 2D material systems, silicene nanosheets (SNSs), which feature an intriguing physiochemical nature for photo-triggered therapeutics and diagnostic imaging and greatly favorable biological effects of biocompatibility and biodegradation. In combination with DFT-based molecular dynamics (MD) calculations, the underlying mechanism of silicene interactions with bio-milieu and its degradation behavior are probed under specific simulated physiological conditions. This work introduces a new form of silicon-based biomaterials with 2D structure featuring biodegradability, biocompatibility, and multifunctionality for theranostic nanomedicine, which is expected to promise high clinical potentials.


Assuntos
Neoplasias/diagnóstico , Neoplasias/terapia , Silício/química , Silício/uso terapêutico , Nanomedicina Teranóstica , Teoria da Densidade Funcional , Modelos Moleculares , Conformação Molecular , Silício/metabolismo
18.
J Am Chem Soc ; 141(29): 11531-11539, 2019 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-31251050

RESUMO

The antitumor activity of disulfiram (DSF), a traditional US Food and Drug Administration-approved drug for the treatment of "alcohol-dependence", is Cu2+-dependent, but the intrinsic anfractuous biodistribution of copper in the human body and copper toxicity induced by exogenous copper supply have severely hindered its in vivo application. Herein, we report an in situ Cu2+ chelation-enhanced DSF-based cancer chemotherapy technique, using a tumor-specific "nontoxicity-to-toxicity" transition strategy based on hollow mesoporous silica nanoparticles as the functional carrier. Cu2+-doped, DSF-loaded hollow mesoporous silica nanoparticles were constructed for the rapid release of Cu2+ ions induced by the mild acidic conditions of the tumor microenvironment. This resulted in the rapid biodegradation of the nanoparticles and accelerated DSF release once the particles were endocytosed into tumor cells. The resulting in situ chelation reaction between the coreleased Cu2+ ions and DSF generated toxic CuET products and concurrently, Fenton-like reactions between the generated Cu+ ions and the high levels of H2O2 resulted in the production of reactive oxygen species (ROS) in the acidic tumor microenvironment. Both in vitro cellular assays and in vivo tumor-xenograft experiments demonstrated the efficient Cu-enhanced and tumor-specific chemotherapeutic efficacy of DSF, with cocontributions from highly toxic CuET complexes and ROS generated within tumors. This work provides a conceptual advancement of nanoparticle-enabled "nontoxicity-to-toxicity" transformation in tumors, to achieving high chemotherapeutic efficacy and biosafety.


Assuntos
Antineoplásicos/farmacologia , Cobre/farmacocinética , Dissulfiram/farmacologia , Portadores de Fármacos/administração & dosagem , Nanopartículas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Linhagem Celular Tumoral , Quelantes/farmacocinética , Quelantes/farmacologia , Dissulfiram/administração & dosagem , Dissulfiram/efeitos adversos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Endocitose/efeitos dos fármacos , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Dióxido de Silício/química , Distribuição Tecidual , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Nat Commun ; 10(1): 2025, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31048681

RESUMO

Combined checkpoint blockade (e.g., PD1/PD-L1) with traditional clinical therapies can be hampered by side effects and low tumour-therapeutic outcome, hindering broad clinical translation. Here we report a combined tumour-therapeutic modality based on integrating nanosonosensitizers-augmented noninvasive sonodynamic therapy (SDT) with checkpoint-blockade immunotherapy. All components of the nanosonosensitizers (HMME/R837@Lip) are clinically approved, wherein liposomes act as carriers to co-encapsulate sonosensitizers (hematoporphyrin monomethyl ether (HMME)) and immune adjuvant (imiquimod (R837)). Using multiple tumour models, we demonstrate that combining nanosonosensitizers-augmented SDT with anti-PD-L1 induces an anti-tumour response, which not only arrests primary tumour progression, but also prevents lung metastasis. Furthermore, the combined treatment strategy offers a long-term immunological memory function, which can protect against tumour rechallenge after elimination of the initial tumours. Therefore, this work represents a proof-of-concept combinatorial tumour therapeutics based on noninvasive tumours-therapeutic modality with immunotherapy.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Metástase Neoplásica/terapia , Neoplasias/terapia , Terapia por Ultrassom/métodos , Animais , Antineoplásicos Imunológicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Linhagem Celular Tumoral/transplante , Terapia Combinada/métodos , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Hematoporfirinas/administração & dosagem , Humanos , Imiquimode/administração & dosagem , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Metástase Neoplásica/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Resultado do Tratamento
20.
ACS Appl Mater Interfaces ; 11(22): 19712-19723, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31066264

RESUMO

Photonic cancer hyperthermia has been considered to be one of the most representative noninvasive cancer treatments with high therapeutic efficiency and biosafety. However, it still remains a crucial challenge to develop efficient photothermal nanoagents with satisfactory photothermal performance and biocompatibility, among which two-dimensional (2D) ultrathin nanosheets have recently been regarded as the promising multifunctional theranostic agents for photothermal tumor ablation. In this work, we report, for the first time, on the construction of a novel kind of photothermal agents based on the intriguing 2D antimony(III) selenide (Sb2Se3) nanosheets for highly efficient photoacoustic imaging-guided photonic cancer hyperthermia by near-infrared (NIR) laser activation. These Sb2Se3 nanosheets were easily fabricated by a novel but efficiently combined liquid nitrogen pretreatment and freezing-thawing approach, which were featured with high photothermal-conversion capability (extinction coefficient: 33.2 L g-1 cm-1; photothermal-conversion efficiency: 30.78%). The further surface engineering of these Sb2Se3 ultrathin nanosheets with poly(vinyl pyrrolidone) (PVP) substantially improved the biocompatibility of the nanosheets and their stability in physiological environments, guaranteeing the feasibility in photonic antitumor applications. Importantly, 2D Sb2Se3-PVP nanosheets have been certificated to efficiently eradicate the tumors by NIR-triggered photonic tumor hyperthermia. Especially, the biosafety in vitro and in vivo of these Sb2Se3 ultrathin nanosheets has been evaluated and demonstrated. This work meaningfully expands the biomedical applications of 2D bionanoplatforms with a planar topology through probing into new members (Sb2Se3 in this work) of 2D biomaterials with unique intrinsic physiochemical property and biological effect.


Assuntos
Antimônio/química , Substâncias Macromoleculares/química , Nanopartículas/química , Selênio/química , Nanomedicina Teranóstica/métodos , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Humanos , Microscopia Eletrônica de Varredura , Fototerapia/métodos , Polivinil/química , Pirrolidinas/química
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