RESUMEN
Narrow photo-absorption range and low carrier utilization are significant barriers that restrict the antitumor efficiency of 2D bismuth oxyhalide (BiOX, X = Cl, Br, I) nanosheets (NSs). Introducing oxygen vacancy (OV) defects can expand the absorption range and improve carrier utilization, which are crucial but also challenging. In this study, a series of BiOxCl NSs with different OV defect concentrations (x = 1, 0.7, 0.5) is developed, which shows full spectrum absorption and strong absorption in the second near-infrared region (NIR-II). Density functional theory calculations are utilized to calculate the crystal structure and density states of BiOxCl, which confirm that part of the carriers is separated by OV enhanced internal electric field to improve carrier utilization. The carriers without redox reaction can be trapped in the OV, leading to great majority of photo-generated carriers promoting the photothermal performance. Triggered by single NIR-II (1064 nm), BiOxCl NSs' bidirectional efficient utilization of carriers achieves synchronously combined phototherapy, leading to enhanced tumor ablation and multimodal diagnostic in vitro and vivo. It is thus believed that this work provides an innovative strategy to design and construct nanoplatforms of indirect band gap semiconductors for clinical phototheranostics.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , Oxígeno/química , Fototerapia/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Imagen Multimodal , Nanopartículas/química , Nanomedicina Teranóstica/métodos , Línea Celular TumoralRESUMEN
The recently emerging bismuth oxyhalide (BiOX) nanomaterials are promising indirect band gap photosensitizer for ultraviolet (UV) light-triggered phototherapy due to their unique layered nanosheet structure. However, the low absorption and poor photothermal conversion efficiency have always impeded their further applications in cancer clinical therapy. Herein, BiOCl rich in oxygen vacancies has been reported to have full-spectrum absorption properties, making it possible to achieve photothermal property under near-infrared laser. Under 808 nm irradiation, the photothermal conversion efficiency of black BiOCl nanosheets (BBNs) is up to 40%. BBNs@PEG can effectively clear primary subcutaneous tumors and prevent recurrence, achieving good synergistic treatment effect. These results not only broke the limitation of UV on the BiOCl material and provided a good template for other semiconductor materials, but also represent a promising approach to fabricate BBN@PEG a novel, potent and multifunctional theranostic platform for precise photothermal therapy and prognostic evaluation.
RESUMEN
The absence of effective therapeutic targets and tumor hypoxia are the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Biomimetic nanotechnology and tumor microenvironment (TME) responsiveness bring hope and opportunity to address this problem. Here, we develop a core membrane nanoplatform (HM/D-I-BL) using hollow mesoporous manganese dioxide (HM) coated with a biomimetic cancer cell membrane for enhanced chemotherapy/phototherapy via the strategy of precise drug delivery and hypoxia amelioration. Cancer cell membrane modification endows HM/D-I-BL with excellent homologous targeting and immune escape performance. Cellular uptake and fluorescence imaging studies confirmed that HM/D-I-BL can be accurately delivered to tumor sites. HM/D-I-BL also features efficient in situ O2 generation in tumors upon laser irradiation, and subsequently enhanced chemotherapy/phototherapy, pointing to its usefulness as a TME-responsive nanozyme to alleviate tumor hypoxia in the presence of H2O2. In addition, HM/D-I-BL showed good fluorescence and magnetic resonance imaging performances, which offers a reliable multimodal image-guided combination tumor therapy for precision theranostics in the future. In general, this intelligent biomimetic nanoplatform with its homotypic tumor targeting, in situ alleviation of tumor hypoxia and synergetic chemophototherapy would open up a new dimension for the precision treatment of TNBC.
Asunto(s)
Nanopartículas , Fotoquimioterapia , Neoplasias de la Mama Triple Negativas , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Humanos , Peróxido de Hidrógeno/farmacología , Fototerapia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Microambiente TumoralRESUMEN
Photothermal therapy (PTT), as an important noninvasive and effective tumor treatment method, has been extensively developed into a powerful cancer therapeutic technique. Nevertheless, the low photothermal conversion efficiency and the limited tissue penetration of typical photothermal therapeutic agents in the first near-infrared (NIR-I) region (700-950 nm) are still the major barriers for further clinical application. Here, we proposed an organic/inorganic dual-PTT agent of synergistic property driven by polydopamine-modified black-titanium dioxide (b-TiO2@PDA) with excellent photoconversion efficiency in the second NIR (NIR-II) region (1000-1500 nm). More specifically, the b-TiO2 treated with sodium borohydride produced excessive oxygen vacancies resulting in oxygen vacancy band that narrowed the b-TiO2 band gap, and the small band gap led to NIR-II region wavelength (1064 nm) absorbance. Furthermore, the combination of defect energy level trapping carrier recombination heat generation and conjugate heat generation mechanism, significantly improved the photothermal performance of the PTT agent based on b-TiO2. The photothermal properties characterization indicated that the proposed dual-PTT agent possesses excellent photothermal performance and ultra-high photoconversion efficiency of 64.9% under 1064 nm laser irradiation, which can completely kill esophageal squamous cells. Meanwhile, Gd2O3 nanoparticles, an excellent magnetic resonance imaging (MRI) agent, were introduced into the nanosystem with similar dotted core-shell structure to enable the nanosystem achieve real-time MRI-monitored cancer therapeutic performance. We believe that this integrated nanotherapeutic system can not only solve the application of PTT in the NIR-II region, but also provide certain theoretical guidance for the clinical diagnosis and treatment of esophageal cancer.
RESUMEN
Unlike stable atherosclerotic plaques, vulnerable plaques are very likely to cause serious cardio-cerebrovascular diseases. Meanwhile, how to non-invasively identify vulnerable plaques at early stages has been an urgent but challenging problem in clinical practices. Here, we propose a macrophage-targeted and in situ stimuli-triggered T1-T2 switchable magnetic resonance imaging (MRI) nanoprobe for the non-invasive diagnosis of vulnerable plaques. Precisely, single-dispersed iron oxide nanoparticles (IONPs) modified with hyaluronic acid (HA), denoted as IONP-HP, show macrophage targetability and T1 MRI enhancement (r2/r1 = 3.415). Triggered by the low pH environment of macrophage lysosomes, the single-dispersed IONP-HP transforms into a cluster analogue, which exhibits T2 MRI enhancement (r2/r1 = 13.326). Furthermore, an in vivo switch of T1-T2 enhancement modes shows that the vulnerable plaques exhibit strong T1 enhancement after intravenous administration of the nanoprobe, followed by a switch to T2 enhancement after 9 h. In contrast, stable plaques show only slight T1 enhancement but without T2 enhancement. It is therefore imperative that the intelligent and novel nanoplatform proposed in this study achieves a substantial non-invasive diagnosis of vulnerable plaques by means of a facile but effective T1-T2 switchable process, which will significantly contribute to the application of materials science in solving clinical problems.
Asunto(s)
Medios de Contraste , Placa Aterosclerótica , Humanos , Imagen por Resonancia Magnética , Placa Amiloide , Placa Aterosclerótica/diagnóstico por imagenRESUMEN
Malignant melanoma, one of the most aggressive types of cancer easily metastasizes, making it extremely difficult to treat and unresponsive to current therapies. Recent breakthroughs in nanomaterials-based cancer immunotherapy have provided potential specific strategy for tumor and metastasis inhibition. With the development of nanotechnology, inorganic nanomaterials have been increasingly studied for their potential cancer therapeutic and molecular imaging functions. However, only iron-based nanomaterials have been approved by the Food and Drug Administration (FDA) in inorganic nanomedicines. For promising clinical application, a new type of nanocomposite is engineered by combining ultra-small iron oxide nanoparticles (Fe3O4 NPs) and ovalbumin (OVA), denoted as Fe3O4-OVA nanocomposites in this study. Interestingly, this is the first time that Fe3O4 NPs are found as nano-immunopotentiators helping nanocomposites efficiently stimulate dendritic cell-based immunotherapy and potentially-activate macrophages. These nanocomposites efficiently stimulate the maturation level of bone marrow derived dendritic cell (BMDCs) and corresponding activation of T cells and also potentially-activate macrophages. With the help of the Fe3O4 nano-immunopotentiators (Fe3O4 NPs), this therapeutic and prophylactic Fe3O4-OVA vaccine can not only efficiently inhibit the subcutaneous and metastatic B16-OVA tumor growth but also successfully prevent the formation of subcutaneous and metastatic tumor, providing a promising strategy for expanding the clinical use of Fe-based nanomaterials.
Asunto(s)
Compuestos Férricos/química , Inmunoterapia/métodos , Neoplasias Pulmonares/prevención & control , Melanoma/patología , Neoplasias Cutáneas/terapia , Animales , Antígenos de Neoplasias/inmunología , Materiales Biocompatibles/química , Células de la Médula Ósea/citología , Células Dendríticas/citología , Femenino , Humanos , Neoplasias Pulmonares/secundario , Macrófagos/citología , Melanoma/terapia , Melanoma Experimental , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Microscopía Fluorescente , Nanomedicina/métodos , Metástasis de la Neoplasia , Células RAW 264.7 , Neoplasias Cutáneas/patología , Rayos XRESUMEN
The efficiency of chemical intercommunication between enzymes in natural networks can be significantly enhanced by the organized catalytic cascades. Nevertheless, the exploration of two-or-more-enzymes-engineered nanoreactors for catalytic cascades remains a great challenge in cancer therapy because of the inherent drawbacks of natural enzymes. Here, encouraged by the catalytic activity of the individual nanozyme for benefiting the treatment of solid tumors, we propose an organized in situ catalytic cascades-enhanced synergistic therapeutic strategy driven by dual-nanozymes-engineered porphyrin metal-organic frameworks (PCN). Precisely, catalase-mimicking platinum nanoparticles (Pt NPs) were sandwiched by PCN, followed by embedding glucose oxidase-mimicking ultrasmall gold nanoparticles (Au NPs) within the outer shell, and further coordination with folic acid (P@Pt@P-Au-FA). The Pt NPs effectively enabled tumor hypoxia relief by catalyzing the intratumoral H2O2 to O2 for (1) enhancing the O2-dependent photodynamic therapy and (2) subsequently accelerating the depletion of ß-d-glucose by Au NPs for synergistic starving-like therapy with the self-produced H2O2 as the substrate for Pt NPs. Consequently, a remarkably strengthened antitumor efficiency with prevention of tumor recurrence and metastasis was achieved. This work highlights a rationally designed tumor microenvironment-specific nanoreactor for opening improved research in nanozymes and provides a means to design a catalytic cascade model for practical applications.