RESUMEN
Hollow mesoporous organosilica nanoparticles (HMONs) are widely considered as a promising drug nanocarrier, but the loaded drugs can easily leak from HMONs, resulting in the considerably decreased drug loading capacity and increased biosafety risk. This study reports the smart use of core/shell Fe3O4/Gd2O3 (FG) hybrid nanoparticles as a gatekeeper to block the pores of HMONs, which can yield an unreported large loading content (up to 20.4%) of DOX. The conjugation of RGD dimer (R2) onto the DOX-loaded HMON with FG capping (D@HMON@FG@R2) allowed for active tumor-targeted delivery. The aggregated FG in D@HMON@FG@R2 could darken the normal tissue surrounding the tumor due to the high r2 value (253.7 mM-1 s-1) and high r2/r1 ratio (19.13), and the intratumorally released FG as a result of reducibility-triggered HMON degradation could brighten the tumor because of the high r1 value (20.1 mM-1 s-1) and low r2/r1 ratio (7.01), which contributed to high contrast magnetic resonance imaging (MRI) for guiding highly efficient tumor-specific DOX release and chemotherapy.
Asunto(s)
Nanopartículas , Fototerapia , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Imagen por Resonancia Magnética , Nanopartículas/uso terapéutico , Fototerapia/métodos , PolímerosRESUMEN
Continuous irradiation during photodynamic therapy (PDT) inevitably induces tumor hypoxia, thereby weakening the PDT effect. In PDT-induced hypoxia, providing singlet oxygen from stored chemical energy may enhance the cell-killing effect and boost the therapeutic effect. Herein, we present a phototheranostic (DPPTPE@PEG-Py NPs) prepared by using a 2-pyridone-based diblock polymer (PEG-Py) to encapsulate a semiconducting, heavy-atom-free pyrrolopyrrolidone-tetraphenylethylene (DPPTPE) with high singlet-oxygen-generation ability both in dichloromethane and water. The PEG-Py can trap the 1 O2 generated from DPPTPE under laser irradiation and form a stable intermediate of endoperoxide, which can then release 1 O2 in the dark, hypoxic tumor microenvironment. Furthermore, fluorescence-imaging-guided phototherapy demonstrates that this phototheranostic could completely inhibit tumor growth with the help of laser irradiation.
Asunto(s)
Oscuridad , Fototerapia/métodos , Oxígeno Singlete/metabolismo , Hipoxia Tumoral/efectos de la radiación , Microambiente Tumoral/efectos de la radiación , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Humanos , Rayos Láser , Imagen Óptica , Polietilenglicoles/química , Pirrolidinonas/química , Oxígeno Singlete/química , Estilbenos/químicaRESUMEN
Gd chelates have occupied most of the market of magnetic resonance imaging (MRI) contrast agents for decades. However, there have been some problems (nephrotoxicity, non-specificity, and low r1 ) that limit their applications. Herein, a wet-chemical method is proposed for facile synthesis of poly(acrylic acid) (PAA) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GON-PAA) with an excellent water dispersibility and a size smaller than 2.0 nm, which is a powerful T1 -weighted MRI contrast agent for diagnosis of diseases due to its remarkable relaxivities (r1 = 70.2 ± 1.8 mM-1 s-1 , and r2 /r1 = 1.02 ± 0.03, at 1.5 T). The r1 is much higher and the r2 /r1 is lower than that of the commercial Gd chelates and reported gadolinium oxide nanoparticles (GONs). Further ES-GON-PAA is developed with conjugation of RGD2 (RGD dimer) (i.e., ES-GON-PAA@RGD2) for T1 -weighted MRI of tumors that overexpress RGD receptors (i.e., integrin αv ß3 ). The maximum signal enhancement (ΔSNR) for T1 -weighted MRI of tumors reaches up to 372 ± 56% at 2 h post-injection of ES-GON-PAA@RGD2, which is much higher than commercial Gd-chelates (<80%). Due to the high biocompatibility and high tumor accumulation, ES-GON-PAA@RGD2 with remarkable relaxivities is a promising and powerful T1 -weighted MRI contrast agent.
Asunto(s)
Gadolinio/química , Imagen por Resonancia Magnética , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Tamaño de la Partícula , Resinas Acrílicas/química , Línea Celular Tumoral , Humanos , Nanopartículas/ultraestructuraRESUMEN
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
Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency.
Asunto(s)
Imagen Multimodal/métodos , Nanopartículas/química , Accidente Cerebrovascular/diagnóstico por imagen , Animales , Supervivencia Celular/efectos de los fármacos , Medios de Contraste/efectos adversos , Medios de Contraste/química , Corazón/efectos de los fármacos , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Pulmón/efectos de los fármacos , Imagen por Resonancia Magnética , Masculino , Ratones , Nanopartículas/efectos adversos , Polietilenglicoles , Células RAW 264.7 , Bazo/efectos de los fármacosRESUMEN
Nanomedicine-enhanced immunogenic cell death (ICD) has attracted considerable attention for its great potential in cancer treatment. Even though polyethylene glycol (PEG) is widely recognized as the gold standard for surface modification of nanomedicines, some shortcomings associated with this PEGylation, such as hindered cell endocytosis and accelerated blood clearance phenomenon, have been revealed in recent years. Notably, polysarcosine (PSar) as a highly biocompatible polymer can be finely synthesized by mild ring-opening polymerization (ROP) of sarcosine N-carboxyanhydrides (Sar-NCAs) and exhibit great potential as an alternative to PEG. In this article, PSar-b-polycamptothecin block copolymers are synthesized by sequential ROP of camptothecin-based NCAs (CPT-NCAs) and Sar-NCAs. Then, the detailed and systematic comparison between PEGylation and PSarylation against the 4T1 tumor model indicates that PSar decoration can facilitate the cell endocytosis, greatly enhancing the ICD effects and antitumor efficacy. Therefore, it is believed that this well-developed PSarylation technique will achieve effective and precise cancer treatment in the near future.
Asunto(s)
Neoplasias , Péptidos , Polietilenglicoles , Sarcosina/análogos & derivados , Humanos , Camptotecina , Muerte Celular Inmunogénica , PolímerosRESUMEN
Inhibiting the myofibroblast differentiation of lung-resident mesenchymal stem cells (LR-MSCs) is a promising yet challenging approach for pulmonary fibrosis (PF) therapy. Here, micelles formed by a graft copolymer of multiple PEGs modified branched polyethylenimine are used for delivering runt-related transcription factor-1 (RUNX1) small interfering RNA (siRNA) (siRUNX1) to the lung, aiming to inhibit the myofibroblast differentiation of LR-MSCs. LR-MSC targeting is achieved by functionalizing the micelle surface with an anti-stem-cell antigen-1 antibody fragment (Fab'). Consequently, therapeutic benefits are obtained by successful suppression of myofibroblast differentiation of LR-MSCs in bleomycin-induced PF model mice treated with siRUNX1-loaded micelles. Furthermore, an excellent synergistic effect of PF therapy is achieved for this micelle system loaded siRUNX1 and glioma-associated oncogene homolog-1 (Gli1) small interfering RNA (siGli1), a traditional anti-PF siRNA of glioma-associated oncogene homolog-1. Hence, this work not only provides RUNX1 as a novel PF therapeutic target, but also as a promising dual siRNA-loaded nanocarrier system for the therapy of PF.
Asunto(s)
Portadores de Fármacos/química , Polímeros/química , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/terapia , ARN Interferente Pequeño/química , ARN Interferente Pequeño/genética , Animales , Ratones , MicelasRESUMEN
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has shown great potential in biomedical applications. Although physical approaches, viruses, and some nonviral vectors have been employed for CRISPR/Cas9 delivery and induce some promising genome-editing efficacy, precise genome editing remains challenging and has not been reported yet. Herein, second near-infrared window (NIR-II) imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 genome-editing strategy is reported based on a rationally designed semiconducting polymer brush (SPPF). SPPF can not only be a vector to deliver CRISPR/Cas9 cassettes but also controls the endolysosomal escape and payloads release through photothermal conversion under laser irradiation. Upon laser exposure, the nanocomplex of SPPF and CRISPR/Cas9 cassettes induces effective site-specific precise genome editing both in vitro and in vivo with minimal toxicity. Besides, NIR-II imaging based on SPPF can also be applied to monitor the in vivo distribution of the genome-editing system and guide laser irradiation in real time. Thus, this study offers a typical paradigm for NIR-II imaging-guided NIR-light-triggered remote control of the CRISPR/Cas9 system for precise genome editing. This strategy may open an avenue for CRISPR/Cas9 genome-editing-based precise gene therapy in the near future.
Asunto(s)
Sistemas CRISPR-Cas , Polietilenglicoles/química , Polietileneimina/química , Animales , Edición Génica , Vectores Genéticos , Células HCT116 , Humanos , Rayos Infrarrojos , Rayos Láser , Ratones Desnudos , SemiconductoresRESUMEN
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 â¢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 â¢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.
Asunto(s)
Antineoplásicos/administración & dosificación , Quimioradioterapia/métodos , Portadores de Fármacos/síntesis química , Liberación de Fármacos/efectos de la radiación , Neoplasias/terapia , Animales , Monóxido de Carbono/química , Femenino , Células Hep G2 , Humanos , Radical Hidroxilo/química , Radical Hidroxilo/efectos de la radiación , Compuestos de Hierro/administración & dosificación , Ratones , Ratones Desnudos , Nanopartículas/química , Compuestos de Organosilicio/síntesis química , Tamaño de la Partícula , Polietilenglicoles/química , Porosidad , Células RAW 264.7 , Resultado del Tratamiento , Rayos X , Ensayos Antitumor por Modelo de Xenoinjerto , terc-Butilhidroperóxido/administración & dosificación , terc-Butilhidroperóxido/efectos de la radiaciónRESUMEN
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.
Asunto(s)
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
Persistent luminescence nanoparticles (PLNPs) have been used for bioimaging without autofluorescence background interference, but the poor afterglow performance impedes their further applications in cancer therapy. To overcome the Achilles' heel of PLNPs, herein we report the construction of injectable persistent luminescence implants (denoted as PL implants) as a built-in excitation source for efficient repeatable photodynamic therapy (PDT). The injectable ZGC (ZnGa1.996O4:Cr0.004) PL implants were prepared by dissolving ZGC PLNPs in poly(lactic-co-glycolic acid)/N-methylpyrrolidone oleosol, which demonstrated much stronger persistent luminescence (PersL) intensity and longer PersL lifetime than that of ZGC PLNPs both in vitro and in vivo. More importantly, the intratumorally fixed ZGC PL implants can serve as a built-in excitation source for repeatable light emitting diode (LED) and PersL-excited PDT upon and after periodic LED irradiation, which leads to the overall improvement of therapeutic effectiveness for efficient tumor growth suppression. This work represents efficient repeatable PDT based on the injectable yet periodically rechargeable ZGC PL implants.
Asunto(s)
Cromo/uso terapéutico , Galio/uso terapéutico , Sustancias Luminiscentes/uso terapéutico , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Zinc/uso terapéutico , Animales , Línea Celular Tumoral , Cromo/administración & dosificación , Cromo/química , Galio/administración & dosificación , Galio/química , Humanos , Inyecciones , Luminiscencia , Sustancias Luminiscentes/administración & dosificación , Sustancias Luminiscentes/química , Ratones , Nanopartículas/administración & dosificación , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/administración & dosificación , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/uso terapéutico , Zinc/administración & dosificación , Zinc/químicaRESUMEN
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
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
The recently emerged exceedingly small magnetic iron oxide nanoparticles (ES-MIONs) (<5 nm) are promising T1-weighted contrast agents for magnetic resonance imaging (MRI) due to their good biocompatibility compared with Gd-chelates. However, the best particle size of ES-MIONs for T1 imaging is still unknown because the synthesis of ES-MIONs with precise size control to clarify the relationship between the r1 (or r2/r1) and the particle size remains a challenge. In this study, we synthesized ES-MIONs with seven different sizes below 5 nm and found that 3.6 nm is the best particle size for ES-MIONs to be utilized as T1-weighted MR contrast agent. To enhance tumor targetability of theranostic nanoparticles and reduce the nonspecific uptake of nanoparticles by normal healthy cells, we constructed a drug delivery system based on the 3.6 nm ES-MIONs for T1-weighted tumor imaging and chemotherapy. The laser scanning confocal microscopy (LSCM) and flow cytometry analysis results demonstrate that our strategy of precise targeting via exposure or hiding of the targeting ligand RGD2 on demand is feasible. The MR imaging and chemotherapy results on the cancer cells and tumor-bearing mice reinforce that our DOX@ES-MION3@RGD2@mPEG3 nanoparticles are promising for high-resolution T1-weighted MR imaging and precise chemotherapy of tumors.
Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas de Magnetita/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Animales , Línea Celular Tumoral , Medios de Contraste/química , Medios de Contraste/uso terapéutico , Imagen de Difusión por Resonancia Magnética , Compuestos Férricos/química , Compuestos Férricos/uso terapéutico , Humanos , Nanopartículas de Magnetita/química , Ratones , Neoplasias/patología , Polietilenglicoles/química , Polietilenglicoles/uso terapéutico , Nanomedicina Teranóstica/métodosRESUMEN
Multidrug resistance (MDR) is responsible for the relatively low effectiveness of chemotherapeutics. Herein, a nitric oxide (NO) gas-enhanced chemosensitization strategy is proposed to overcome MDR by construction of a biodegradable nanomedicine formula based on BNN6/DOX coloaded monomethoxy(polyethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA). On one hand, the nanomedicine features high biocompatibility due to the high density of PEG and biodegradable PLGA. On the other hand, the nanoformula exhibits excellent stability under physiological conditions but exhibits stimuli-responsive decomposition of BNN6 for NO gas release upon ultraviolet-visible irradiation. More importantly, after NO release is triggered, gas molecules are generated that break the nanoparticle shell and lead to the release of doxorubicin. Furthermore, NO was demonstrated to reverse the MDR of tumor cells and enhance the chemosensitization for doxorubicin therapy.
Asunto(s)
Resistencia a Múltiples Medicamentos/efectos de los fármacos , Nanomedicina/métodos , Óxido Nítrico/farmacología , Línea Celular Tumoral , Doxorrubicina/administración & dosificación , Resistencia a Múltiples Medicamentos/efectos de la radiación , Humanos , Luz , Nanopartículas/administración & dosificación , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Óxido Nítrico/administración & dosificación , Óxido Nítrico/química , Polietilenglicoles/químicaRESUMEN
It is well-known that multimodal imaging can integrate the advantages of different imaging modalities by overcoming their individual limitations. As ultra-high field magnetic resonance imaging (MRI) will be inevitably used in future MRI/X-ray computed tomography (CT) scanner, it is highly expected to develop high-performance nano-contrast agents for ultra-high field MR and CT dual-modality imaging, which has not been reported yet. Moreover, specific behavior of nano-contrast agents for ultra-high field MRI is a challenging work and still remains unknown. Herein, a novel type of NaHoF4 nanoparticles (NPs) with varied particle sizes were synthesized and explored as high-performance dual-modality contrast agents for ultra-high field MR and CT imaging. The specific X-ray absorption and MR relaxivity enhancements with varied nanoparticle diameters (3 nm, 7 nm, 13 nm and 29 nm) under different magnetic field (1.5/3.0/7.0 T) are investigated. Based on experimental results and theoretical analysis, the Curie and dipolar relaxation mechanisms of NaHoF4 NPs are firstly separated. Our results will greatly promote the future medical translational development of the NaHoF4 nano-contrast agents for ultra-high field MR/CT dual-modality imaging applications.
Asunto(s)
Medios de Contraste , Holmio/química , Imagen por Resonancia Magnética/métodos , Nanopartículas , Polietilenglicoles/química , Tomografía Computarizada por Rayos X/métodos , Microscopía Electrónica de Transmisión , Imagen MultimodalRESUMEN
To achieve the accurate diagnosis and efficient in situ therapy of malignant tumors is encouraging but still remains a big challenge. The integration of upconversion nanoparticles and mesoporous silica that can combine the diagnostic/therapeutic functions within a single platform, may provide a more advanced way for the efficient theranostics of cancer. In this study, sub-80 nm rattle-structured multifunctional Gd-UCNPs core/mesoporous silica shell nanotheranostics (UCMSNs) were successfully constructed for the co-delivery of a radio-/photo-sensitizer hematoporphyrin (HP) and a radiosensitizer/chemodrug docetaxel (Dtxl). Upon NIR excitation and X-ray irradiation, the complete tumor elimination has been achieved by the synergetic chemo-/radio-/photodynamic tri-modal therapy under the assistance of simultaneous magnetic/upconversion luminescent (MR/UCL) bimodal imaging. To the best of our knowledge, this study is the first example of achieving tri-modal synergetic therapy in one single nanotheranostic system, and we anticipate that it may serve as a particularly useful platform for the clinical diagnosis and efficient treatment of cancer from bench to beside.