RESUMEN
It is widely accepted that a small particle size and rough surface can enhance tumor tissue accumulation and tumor cellular uptake of nanoparticles, respectively. Herein, sub-50 nm urchin-inspired disulfide bond-bridged mesoporous organosilica nanoparticles (UMONs) featured with a spiky surface and glutathione (GSH)-responsive biodegradability were successfully synthesized by a facile one-pot biphasic synthesis strategy for enhanced cellular internalization and tumor accumulation. l-Arginine (LA) is encapsulated into the mesopores of UMONs, whose outer surface is capped with the gatekeeper of ultrasmall gold nanoparticles, i.e., UMONs-LA-Au. On the one hand, the mild acidity-activated uncapping of ultrasmall gold can realize a tumor microenvironment (TME)-responsive release of LA. On the other hand, the unique natural glucose oxidase (GOx)-mimicking catalytic activity of ultrasmall gold can catalyze the decomposition of intratumoral glucose to produce acidic hydrogen peroxide (H2O2) and gluconic acid. Remarkably, these products can not only further facilitate the release of LA, but also catalyze the LA-H2O2 reaction for an increased nitric oxide (NO) yield, which realizes synergistic catalysis-enhanced NO gas therapy for tumor eradication. The judiciously fabricated UMONs-LA-Au present a paradigm of TME-responsive nanoplatforms for both enhanced cellular uptake and tumor-specific precision cascaded therapy, which broadens the range of practical biomedical applications and holds a significant promise for the clinical translation of silica-based nanotheranostics.
Asunto(s)
Nanopartículas del Metal , Nanopartículas , Oro , Peróxido de Hidrógeno , Tamaño de la Partícula , Dióxido de SilicioRESUMEN
Basal cell carcinoma (BCC), a non-melanoma cancer with high morbidity in the elders, is a type of limited skin cancer with a projected appearance. Traditional treatments such as oral or injection administration are likely to result in serious side effects. Here, we developed a strategy that combined photodynamic therapy (PDT) with ablative light "needles" (carbon-dioxide laser) for the treatment of BCC, involving ß-Tetra-(4-carboxyl-phenoxy)-zinc phthalocyanine (ZnPC4) cubic phases with high drug loading, easy preparation, long local retention, good spreading ability and little toxicity. A model of nude mice with BCC was established for the study of pharmacodynamics. The light needles of low energy (53 mJ/cm2) used here could promote transdermal absorption of ZnPC4 cubic phases while those of high energy (238 mJ/cm2) alone could completely kill tumor cells with no recurrence. However, ZnPC4 cubic phases alone could not completely inhibit tumor growth, for it was distributed mainly at the topical administration site in the absence of any adjuvant technology. Therefore, the combination of photodynamics and light needles offered a good solution. Especially, the combined use of light needles with high energy and ZnPC4 cubic phases can treat BCC efficiently with no recurrence. This approach is expected to be a novel and promising medication against BCC.
Asunto(s)
Carcinoma Basocelular , Fotoquimioterapia , Neoplasias Cutáneas , Administración Tópica , Ácido Aminolevulínico , Animales , Carcinoma Basocelular/tratamiento farmacológico , Ratones , Ratones Desnudos , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológicoRESUMEN
The contents of terrestrosin D and hecogenin from Tribuli Fructus were determined before and after stir-frying. The results showed that the content of terrestrosin D was decreased significantly,and the content of hecogenin was increased significantly after such processing. In order to verify the inference that terrestrosin D was converted to hecogenin by stir-frying,the quantitative variation rules of terrestrosin D and hecogenin were studied by simulated processing technology,and the simulated processing product of terrestrosin D was qualitatively characterized by ultra performance liquid chromatography/time of flight mass spectrometry( UPLC-TOF/MS) to clarify its transformation process during stir-frying. The results showed that the content of terrestrosin D was decreased significantly at first and then a platform stage appeared with the prolongation of processing time at a certain temperature. Raising the stir-frying temperature could further decrease the content of terrestrosin D and delay the time that the platform stage appeared. When the processing was simulated at higher temperatures( 220 â and 240 â),the content of hecogenin was increased gradually with the increase of processing temperature and the prolongation of processing time. In the process of stir-frying,the deglycosylation reaction of terrestrosin D to hecogenin was not completed in one step. The deglycosylation reaction occurred first at the end of the sugar chain,and then other glycosyl units in the sugar chain were sequentially removed from the outside to the inside to finally form the hecogenin. This study provides a basis for further revealing the detoxification mechanism of stir-fried Tribuli Fructus.
Asunto(s)
Frutas/química , Sapogeninas/análisis , Zygophyllaceae/química , Cromatografía Liquida , Calor , Fitoquímicos/análisis , Espectrometría de Masas en TándemRESUMEN
This article describes a nanoplatform based on matrix metalloproteinase (MMP)-responsive gold nanoparticles (AuNPs) for tumor-targeted photoacoustic (PA) imaging-guided photothermal therapy and drug delivery. AuNPs were grafted with complementary DNA strands, tethered with doxorubicin and coated with poly(ethylene glycol) via a thermal-labile linker and a MMP-cleavable peptide, respectively. The nanoprobes remained well-isolated in healthy tissues, but formed aggregates rapidly under MMP-abundant conditions. The DNA hybridization-induced assembly of the nanoprobes led to prolonged tumor retention and strong near-infrared (NIR) absorption, which is beneficial to deep-tissue imaging and therapy. Compared with MMP-inert nanoprobes, our platform demonstrated significantly enhanced efficiency in PA imaging and photothermal conversion upon NIR irradiation. Meanwhile, doxorubicin could be released rapidly in response to the localized elevation of temperature, leading to synergistic chemo-photothermal therapy. The unique nanoplatform may find applications in effective disease control by delivering imaging and therapy to tumors with high specificity, safety, and universality.
Asunto(s)
Oro/química , Metaloproteinasas de la Matriz/química , Nanopartículas del Metal/química , Neoplasias/terapia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animales , Línea Celular Tumoral , Medios de Cultivo , ADN/química , Doxorrubicina/química , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Hipertermia Inducida , Ratones , Nanopartículas/química , Trasplante de Neoplasias , Polietilenglicoles/química , Espectroscopía Infrarroja Corta , Nanomedicina TeranósticaRESUMEN
2D nanomaterials have attracted broad interest in the field of biomedicine owing to their large surface area, high drug-loading capacity, and excellent photothermal conversion. However, few studies report their "enzyme-like" catalytic performance because it is difficult to prepare enzymatic nanosheets with small size and ultrathin thickness by current synthetic protocols. Herein, a novel one-step wet-chemical method is first proposed for protein-directed synthesis of 2D MnO2 nanosheets (M-NSs), in which the size and thickness can be easily adjusted by the protein dosage. Then, a unique sono-chemical approach is introduced for surface functionalization of the M-NSs with high dispersity/stability as well as metal-cation-chelating capacity, which can not only chelate 64 Cu radionuclides for positron emission tomography (PET) imaging, but also capture the potentially released Mn2+ for enhanced biosafety. Interestingly, the resulting M-NS exhibits excellent enzyme-like activity to catalyze the oxidation of glucose, which represents an alternative paradigm of acute glucose oxidase for starving cancer cells and sensitizing them to thermal ablation. Featured with outstanding phototheranostic performance, the well-designed M-NS can achieve effective photoacoustic-imaging-guided synergistic starvation-enhanced photothermal therapy. This study is expected to establish a new enzymatic phototheranostic paradigm based on small-sized and ultrathin M-NSs, which will broaden the application of 2D nanomaterials.
Asunto(s)
Compuestos de Manganeso/química , Nanoestructuras/química , Neoplasias/diagnóstico , Neoplasias/terapia , Óxidos/química , Fototerapia/métodos , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Materiales Biomiméticos/síntesis química , Materiales Biomiméticos/metabolismo , Catálisis , Línea Celular Tumoral , Medios de Contraste/química , Cobre/química , Humanos , Marcaje Isotópico/métodos , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Oxidación-Reducción/efectos de los fármacos , Tamaño de la Partícula , Tomografía de Emisión de Positrones/métodos , Propiedades de Superficie , Nanomedicina Teranóstica/métodos , Agua/químicaRESUMEN
The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.
Asunto(s)
Hipertermia Inducida , Nanopartículas/química , Neoplasias/diagnóstico , Neoplasias/terapia , Técnicas Fotoacústicas , Fototerapia , Nanomedicina Teranóstica , HumanosRESUMEN
Featured with a large surface area, uniform interpenetrating mesopores, diverse organic framework hybridization, and well-defined surface properties, the hollow mesoporous organosilica nanoparticle (HMON) represents a promising paradigm in drug delivery systems with excellent biocompatibility. However, effective tumor accumulation and precise cancer theranostics of the HMON still remain a challenge. In this study, an "ammonia-assisted hot water etching" method is applied for the successful construction of sub-50 nm thioether/phenylene dual-hybridized HMON with low hemolytic effect. Particularly, the surface modification with Mo(VI)-based polyoxometalate (POM) clusters drives the self-assembly of HMON in the mild acidic tumor microenvironment (TME) to achieve enhanced tumor retention and accumulation. More importantly, the reducibility-activated Mo(VI)-to-Mo(V) conversion within POM not only endows the POM-anchored HMON with outstanding TME-responsive photoacoustic (PA) imaging contrast and photothermal therapy (PTT) performance but also plays an indispensable role in controllably triggering the decomposition of the Mn2(CO)10 payload for CO release, which gives rise to remarkable synergistic PTT-enhanced CO gas therapy for complete tumor eradication. By harnessing the unique acidic and redox properties of TME, the judiciously designed smart POM-anchored HMON nanoplatform is expected to act as a "magic bomb" to selectively destroy cancer without damaging normal tissues. This nanoplatform holds significant potential in realizing TME-responsive self-assembly for enhanced tumor accumulation and precise tumor-specific synergistic therapy, which is very promising for clinical translation.
Asunto(s)
Antineoplásicos/farmacología , Monóxido de Carbono/farmacología , Glioblastoma/tratamiento farmacológico , Nanopartículas/química , Compuestos de Organosilicio/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Monóxido de Carbono/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Glioblastoma/diagnóstico por imagen , Humanos , Ratones , Compuestos de Organosilicio/síntesis química , Compuestos de Organosilicio/química , Tamaño de la Partícula , Técnicas Fotoacústicas , Fototerapia , Porosidad , Propiedades de Superficie , Microambiente Tumoral/efectos de los fármacosRESUMEN
Tumor-specific phototheranostics is conducive to realizing precise cancer therapy. Herein, a novel tumor microenvironment (TME)-responsive phototheranostic paradigm based on the combination of semiconducting polymer brushes and polyoxometalate clusters (SPB@POM) is rationally designed. The acidic TME could drive the self-assembly of SPB@POM into bigger aggregates for enhanced tumor retention and accumulation, while the reducing TME could significantly enhance the NIR absorption of SPB@POM for significant improvement of photoacoustic imaging contrast and photothermal therapy efficacy. Therefore, the smart pH/glutathione (GSH)-responsive SPB@POM allows for remarkable phototheranostic enhancement under the unique TME, which has potential for precise tumor-specific phototheranostics with minimal side effects.
Asunto(s)
Glutatión/química , Neoplasias/terapia , Fototerapia/métodos , Polímeros/química , Semiconductores , Nanomedicina Teranóstica , Compuestos de Tungsteno/química , Humanos , Concentración de Iones de Hidrógeno , Microscopía Electrónica de Transmisión , Polimerizacion , Espectroscopía Infrarroja Corta , Microambiente TumoralRESUMEN
Accurate diagnosis of tumor is promising to guide photothermal therapy (PTT) for efficacious tumor ablation with minimal damage to healthy tissues. Here, we report an activatable dual-modal imaging agent, which is based on PEGylated-gadolinium metallofullerene-polypyrrole nanoparticle (PEG-GMF-PPy NP) for imaging-guided PTT. A contrast agent (gadolinium metallofullerene, GMF) with excellent magnetic resonance imaging (MRI) performance and an ultra-pH-responsive polymer (PEG-PC7A) are successively modified to the surface of photothermal agent (PPy NP). The prepared PEG-GMF-PPy NPs show strong absorption in the near-infrared (NIR) region, so they can be utilized for photoacoustic imaging. Furthermore, in a tumor extracellular environment, the PEG-GMF-PPy NPs can achieve pH-enhanced MRI because of the hydrophobic-to-hydrophilic conversion of the PC7A. Upon accurate diagnosis-guided NIR laser irradiation, excellent tumor ablation effect is achieved. The results suggest that the PEG-GMF-PPy NPs are promising agents for activatable imaging-guided PTT.
Asunto(s)
Nanopartículas , Gadolinio , Fototerapia , Polímeros , PirrolesRESUMEN
Designing nanomaterials with advanced functions and physical properties to improve cancer diagnosis and treatment has been an enormous challenge. In this work, we report the synthesis of magnetic gold nanowreaths (AuNWs) by combining wet-chemical synthesis with layer-by-layer self-assembly. The presence of Au branches, small junctions, and central holes in AuNWs led to improved photothermal effect compared with Au nanoring seeds and thick Au nanoring with smooth surface. The self-assembly of exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) on the surfaces of AuNWs not only effectively quenched the T1-weighted magnetic resonance imaging (MRI) ability due to the enhanced T2 decaying effect but also provided the responsiveness to glutathione (GSH). After intravenous injection, the T1 signal of magnetic AuNWs initially in the "OFF" state can be intelligently switched on in response to the relatively high GSH concentration in tumor, and the formation of larger assemblies of ES-MIONs improved their tumor delivery compared to ES-MIONs themselves. Thus, the magnetic AuNWs showed higher MRI contrast than ES-MIONs or commercial Magnevist in T1-weighted MR imaging of tumor. Furthermore, the magnetic AuNWs have absorption in near-infrared range, leading to strong photoacoustic signal and effective photoablation of tumor. Therefore, our GSH-responsive self-assembled magnetic AuNWs could enhance T1-weighted MRI and photoacoustic imaging of tumor and be used for imaging-guided photothermal therapy.
Asunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Glutatión/química , Oro/química , Nanopartículas del Metal/química , Neoplasias Experimentales/diagnóstico por imagen , Animales , Neoplasias Encefálicas/tratamiento farmacológico , Línea Celular Tumoral , Glioma/tratamiento farmacológico , Humanos , Imagen por Resonancia Magnética , Ratones , Ratones Desnudos , Neoplasias Experimentales/tratamiento farmacológico , FototerapiaRESUMEN
Alleviation of tumor hypoxia has been the premise for improving the effectiveness of radiotherapy, which hinges upon the advanced delivery and rapid release of oxygen within the tumor region. Herein, we propose a "bubble-enhanced oxygen diffusion" strategy to achieve whole tumor oxygenation for significant radiation enhancement based on the "bystander effect". Toward this end, sub-50 nm CuS-modified and 64Cu-labeled hollow mesoporous organosilica nanoparticles were constructed for tumor-specific delivery of O2-saturated perfluoropentane (PFP). Through the aid of PFP gasification arising from NIR laser-triggered mild hyperthermia, simultaneous PET/PA/US multimodality imaging and rapid oxygen diffusion across the tumor can be achieved for remarkable hypoxic radiosensitization. Furthermore, the multifunctional oxygen-carrying nanotheranostics also allow for other oxygen-dependent treatments, thus greatly advancing the development of bubble-enhanced synergistic therapy platforms.
Asunto(s)
Fluorocarburos/uso terapéutico , Nanopartículas/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Compuestos de Organosilicio/uso terapéutico , Oxígeno/metabolismo , Nanomedicina Teranóstica/métodos , Animales , Línea Celular Tumoral , Femenino , Humanos , Hipertermia Inducida/métodos , Ratones , Ratones Desnudos , Nanopartículas/ultraestructura , Neoplasias/radioterapia , Técnicas Fotoacústicas/métodos , Porosidad , Tomografía de Emisión de Positrones/métodos , Ultrasonografía/métodosRESUMEN
The clearance of nanoparticles (NPs) by mononuclear phagocyte system (MPS) from blood leads to high liver and spleen uptake and negatively impacts their tumor delivery efficiency. Here we systematically evaluated the in vitro and in vivo nanobio interactions of a two-dimensional (2D) model, gold (Au) nanorings, which were compared with Au nanospheres and Au nanoplates of similar size. Among different shapes, Au nanorings achieved the lowest MPS uptake and highest tumor accumulation. Among different sizes, 50 nm Au nanorings showed the highest tumor delivery efficiency. In addition, we demonstrated the potential use of Au naonrings in photoacoustic imaging and photothermal therapy. Thus, engineering the shape, surface area, and size of Au nanostructures is important in controlling NP-MPS interactions and improving the tumor uptake efficiency.
Asunto(s)
Antineoplásicos/farmacología , Oro/farmacología , Sistema Mononuclear Fagocítico/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Fototerapia , Animales , Antineoplásicos/química , Diagnóstico por Imagen , Oro/química , Macrófagos/efectos de los fármacos , Ratones , Sistema Mononuclear Fagocítico/inmunología , Neoplasias/diagnóstico , Tamaño de la Partícula , Tomografía de Emisión de Positrones , Células RAW 264.7 , Propiedades de Superficie , Distribución TisularRESUMEN
Although various noble metal and semiconducting molecules have been developed as photoacoustic (PA) agents, the use of semiconducting polymer-metal nanoparticle hybrid materials to enhance PA signal has not been explored. A novel semiconducting-plasmonic nanovesicle was fabricated by self-assembly of semiconducting poly(perylene diimide) (PPDI) and poly(ethylene glycol (PEG) tethered gold nanoparticles (Au@PPDI/PEG). A highly localized and strongly enhanced electromagnetic (EM) field is distributed between adjacent gold nanoparticles in the vesicular shell, where the absorbing collapsed PPDI is present. Significantly, the EM field in turn enhances the light absorption efficiency of PPDI, leading to a much greater photothermal effect and a stronger photoacoustic signal compared to PDI nanoparticle or gold nanovesicle alone. The optical property of the hybrid vesicle can be further tailored by controlling the ratio of PPDI and gold nanoparticle as well as the adjustable interparticle distance of gold nanoparticles localized in the vesicular shell. In vivo imaging and therapeutic evaluation demonstrated that the hybrid vesicle is an excellent probe for cancer theranostics.
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Oro/metabolismo , Hipertermia Inducida/métodos , Nanopartículas/metabolismo , Imagen Óptica/métodos , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animales , Modelos Animales de Enfermedad , Fenómenos Electromagnéticos , Glioblastoma/diagnóstico por imagen , Glioblastoma/terapia , Xenoinjertos , Ratones , Nanomedicina/métodos , Trasplante de Neoplasias , Polietilenglicoles/metabolismo , Resultado del TratamientoRESUMEN
Integration of magnetic resonance imaging (MRI) and other imaging modalities is promising to furnish complementary information for accurate cancer diagnosis and imaging-guided therapy. However, most gadolinium (Gd)-chelator MR contrast agents are limited by their relatively low relaxivity and high risk of released-Gd-ions-associated toxicity. Herein, a radionuclide-64 Cu-labeled doxorubicin-loaded polydopamine (PDA)-gadolinium-metallofullerene core-satellite nanotheranostic agent (denoted as CDPGM) is developed for MR/photoacoustic (PA)/positron emission tomography (PET) multimodal imaging-guided combination cancer therapy. In this system, the near-infrared (NIR)-absorbing PDA acts as a platform for the assembly of different moieties; Gd3 N@C80 , a kind of gadolinium metallofullerene with three Gd ions in one carbon cage, acts as a satellite anchoring on the surface of PDA. The as-prepared CDPGM NPs show good biocompatibility, strong NIR absorption, high relaxivity (r 1 = 14.06 mM-1 s-1 ), low risk of release of Gd ions, and NIR-triggered drug release. In vivo MR/PA/PET multimodal imaging confirms effective tumor accumulation of the CDPGM NPs. Moreover, upon NIR laser irradiation, the tumor is completely eliminated with combined chemo-photothermal therapy. These results suggest that the CDPGM NPs hold great promise for cancer theranostics.
Asunto(s)
Indoles/química , Polímeros/química , Gadolinio , Humanos , Imagen Multimodal , Neoplasias , FototerapiaRESUMEN
Reported procedures on the synthesis of gold nanoshells with smooth surfaces have merely demonstrated efficient control of shell thickness and particle size, yet no branch and nanoporous features on the nanoshell have been implemented to date. Herein, we demonstrate the ability to control the roughness and nanoscale porosity of gold nanoshells by using redox-active polymer poly(vinylphenol)-b-(styrene) nanoparticles as reducing agent and template. The porosity and size of the branches on this branched nanoporous gold nanoshell (BAuNSP) material can be facilely adjusted by control of the reaction speed or the reaction time between the redox-active polymer nanoparticles and gold ions (Au3+). Due to the strong reduction ability of the redox-active polymer, the yield of BAuNSP was virtually 100%. By taking advantage of the sharp branches and nanoporous features, BAuNSP exhibited greatly enhanced physico-optical properties, including photothermal effect, surface-enhanced Raman scattering (SERS), and photoacoustic (PA) signals. The photothermal conversion efficiency can reach as high as 75.5%, which is greater than most gold nanocrystals. Furthermore, the nanoporous nature of the shells allows for effective drug loading and controlled drug release. The thermoresponsive polymer coated on the BAuNSP surface serves as a gate keeper, governing the drug release behavior through photothermal heating. Positron emission tomography imaging demonstrated a high passive tumor accumulation of 64Cu-labeled BAuNSP. The strong SERS signal generated by the SERS-active BAuNSP in vivo, accompanied by enhanced PA signals in the tumor region, provide significant tumor information, including size, morphology, position, and boundaries between tumor and healthy tissues. In vivo tumor therapy experiments demonstrated a highly synergistic chemo-photothermal therapy effect of drug-loaded BAuNSPs, guided by three modes of optical imaging.
Asunto(s)
Oro/química , Nanoporos , Nanocáscaras/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Polímeros/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Femenino , Oro/uso terapéutico , Humanos , Hipertermia Inducida/métodos , Ratones , Nanoporos/ultraestructura , Nanocáscaras/uso terapéutico , Nanocáscaras/ultraestructura , Imagen Óptica/métodos , Oxidación-Reducción , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Polímeros/uso terapéutico , Tomografía de Emisión de Positrones/métodosRESUMEN
The combination of hyperthermia and chemotherapy is able to greatly enhance the treatment efficacy mainly due to the synergistic interactions between these two treatments. In this study, we propose a new concept of mild hyperthermia enhanced chemotherapy to explore and validate the synergistic mechanism in vitro and in vivo. To do this, a novel kind of biodegradable nanotheranostics based on copper sulfide doped periodic mesoporous organosilica nanoparticles (CuS@PMOs) was constructed via an in situ growth method for light-triggered mild hyperthermia and drug delivery. The as-prepared CuS@PMOs exhibit a high doxorubicin (DOX) loading capacity of 470 mg/g. The DOX release from CuS@PMOs can be precisely controlled by three stimuli, including intracellular glutathione (GSH), acidic environment in tumor cells, and external laser irradiation. Most intriguingly, mild hyperthermia induced by laser-irradiated CuS nanoparticles can dramatically improve the cell uptake of nanotheranostics both in vitro and in vivo, thus significantly enhancing the chemotherapeutic efficacy for complete tumor growth suppression without recurrence. Meanwhile, the fluorescence recovery following the DOX release can be used as an indicator to monitor the chemotherapeutic progress.
Asunto(s)
Materiales Biocompatibles/química , Doxorrubicina/uso terapéutico , Hipertermia Inducida , Nanomedicina Teranóstica , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Diagnóstico por Imagen , Doxorrubicina/farmacología , Liberación de Fármacos , Humanos , Ratones , Nanopartículas/química , Nanopartículas/ultraestructura , Porosidad , Dióxido de Silicio/químicaRESUMEN
It is essential to control the size and morphology of nanoparticles strictly in nanomedicine. Protein cages offer significant potential for templated synthesis of inorganic nanoparticles. In this study, we successfully synthesized ultrasmall copper sulfide (CuS) nanoparticles inside the cavity of ferritin (Fn) nanocages by a biomimetic synthesis method. The uniform CuS-Fn nanocages (CuS-Fn NCs) showed strong near-infrared absorbance and high photothermal conversion efficiency. In quantitative ratiometric photoacoustic imaging (PAI), the CuS-Fn NCs exhibited superior photoacoustic tomography improvements for real-time in vivo PAI of entire tumors. With the incorporation of radionuclide (64)Cu, (64)CuS-Fn NCs also served as an excellent PET imaging agent with higher tumor accumulation compared to free copper. Following the guidance of PAI and PET, CuS-Fn NCs were applied in photothermal therapy to achieve superior cancer therapeutic efficiency with good biocompatibility both in vitro and in vivo. The results demonstrate that the bioinspired multifunctional CuS-Fn NCs have potential as clinically translatable cancer theranostics and could provide a noninvasive, highly sensitive, and quantitative in vivo guiding method for cancer photothermal therapies in experimental and clinical settings.