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Surface-enhanced Raman scattering (SERS) imaging integrating photothermal and photodynamic therapy (PTT/PDT) is a promising approach for achieving accurate diagnosis and effective treatment of cancers. However, most available Raman reporters show multiple signals in the fingerprint region, which overlap with background signals from cellular biomolecules. Herein, a 4T1 cell membrane-enveloped gold nanorods-manganese porphyrins system (GMCMs) is designed and successfully fabricated as a biomimetic theranostic nanoplatform. Manganese porphyrins are adsorbed on the surface of Au nanorods via the terminal alkynyl group. Cell membrane encapsulation protects the manganese porphyrins from falling off the gold nanorods. The biomimetic GMCMs confirm specific homologous targeting to 4T1 cells with good dispersibility, excellent photoacoustic (PA) imaging properties, and preferable photothermal and 1O2 generation performance. GMCMs exhibit distinct SERS signals in the silent region without endogenous biomolecule interference both in vitro and in vivo. Manganese ions could not only quench the fluorescence of porphyrins to enhance the SERS imaging effect but also deplete cellular GSH to increase 1O2 yield. Both in vitro and in vivo studies demonstrate that GMCMs effectively eradicate tumors through SERS/PA imaging-guided PTT/PDT. This study provides a feasible strategy for augmenting the Raman imaging effects of the alkynyl group and integrating GSH-depletion to enhance PTT/PDT efficacy.
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An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8+ T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment.
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Hidrogeles , Inmunoterapia , Lectinas Tipo C , Inmunoterapia/métodos , Animales , Hidrogeles/química , Lectinas Tipo C/metabolismo , Humanos , Línea Celular Tumoral , Neoplasias/terapia , Neoplasias/inmunología , Ratones Endogámicos C57BL , Microambiente Tumoral/inmunología , Quitosano/química , Células Presentadoras de Antígenos/inmunología , Vacunas contra el Cáncer/inmunología , Ratones , Proteínas de la Membrana/metabolismo , Receptores Inmunológicos/metabolismo , Linfocitos T CD8-positivos/inmunologíaRESUMEN
Photoacoustic (PA) tomography is an emerging biomedical imaging technology for precision cancer medicine. Conventional small-molecule PA probes usually exhibit a single PA signal and poor tumor targeting that lack the imaging reliability. Here, we introduce a series of cyanine/hemicyanine interconversion dyes (denoted Cy-HCy) for PA/fluorescent dual-mode probe development that features optimized ratiometric PA imaging and tunable tumor-targeting ability for precise diagnosis and resection of colorectal cancer (CRC). Importantly, Cy-HCy can be presented in cyanine (inherent tumor targeting and long NIR PA wavelength) and hemicyanine (poor tumor targeting and short NIR PA wavelength) by fine-tuning torsion angle and the ingenious transformation between cyanine and hemicyanine through regulation optically tunable group endows the NIR ratiometric PA and tunable tumor-targeting properties. To demonstrate the applicability of Cy-HCy dyes, we designed the first small-molecule tumor-targeting and NIR ratiometric PA probe Cy-HCy-H2S for precise CRC liver metastasis diagnosis, activated by H2S (a CRC biomarker). Using this probe, we not only visualized the subcutaneous tumor and liver metastatic cancers in CRC mouse models but also realized PA and fluorescence image-guided tumor excision. We expect that Cy-HCy will be generalized for creating a wide variety of inherently tumor-targeting NIR ratiometric PA probes in oncological research and practice.
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The tumor immunosuppressive microenvironment (TIME) and uncontrollable release of antigens can lower the efficacy of nanovaccine-based immunotherapy (NBI). Therefore, it is necessary to develop a new strategy for TIME reshaping and controllable release of antigens to improve the NBI efficacy. Herein, an acidity-responsive Schiff base-conjugated polyphenol-coordinated nanovaccine was constructed for the first time to realize bidirectional TIME reshaping and controllable release of antigens for activating T cells. In particular, an acidity-responsive tannic acid-ovalbumin (TA-OVA) nanoconjugate was prepared via a Schiff base reaction. FeIII was coordinated with TA-OVA to produce a FeIII-TA-OVA nanosystem, and 1-methyltryptophan (1-MT) as an indoleamine 2,3-dioxygenase inhibitor was loaded to form a polyphenol-coordinated nanovaccine. The coordination between FeIII and TA could cause photothermal ablation of primary tumors, and the acidity-triggered Schiff base dissociation of TA-OVA could controllably release OVA to realize lysosome escape, initiating the body's immune response. More importantly, oxidative stress generated by a tumor-specific Fenton reaction of Fe ions could promote the polarization of tumor-associated macrophages from the M2 to M1 phenotype, resulting in the upregulation of cytotoxic T cells and helper T cells. Meanwhile, 1-MT could downregulate immunosuppressive regulatory T cells. Overall, such skillful combination of bidirectional TIME reshaping and controllable antigen release into one coordination nanosystem could effectively enhance the NBI efficacy of tumors.
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Inmunoterapia , Ovalbúmina , Polifenoles , Bases de Schiff , Taninos , Microambiente Tumoral , Animales , Microambiente Tumoral/efectos de los fármacos , Ovalbúmina/inmunología , Ovalbúmina/química , Ovalbúmina/administración & dosificación , Polifenoles/química , Polifenoles/farmacología , Ratones , Taninos/química , Taninos/farmacología , Bases de Schiff/química , Concentración de Iones de Hidrógeno , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/administración & dosificación , Triptófano/química , Triptófano/análogos & derivados , Nanoconjugados/química , Ratones Endogámicos C57BL , Nanopartículas/química , Línea Celular Tumoral , Compuestos Férricos/química , NanovacunasRESUMEN
Due to the difficulty of accurately characterizing properties such as the molecular weight (Mn) and grafting density (σ) of gradient brushes (GBs), these properties are traditionally assumed to be uniform in space to simplify analysis. Applying a stochastic reaction model (SRM) developed for heterogeneous polymerizations, we explored surface-initiated polymerizations (SIPs) with initiator gradients in lattice Monte Carlo simulations to examine this assumption. An initial exploration of SIPs with 'homogeneously' distributed initiators revealed that increasing σ slows down the polymerization process, resulting in polymers with lower molecular weight and larger dispersity (D) for a given reaction time. In SIPs with an initiator gradient, we observed that the properties of the polymers are position-dependent, with lower Mn and larger D in regions of higher σ, indicating the non-uniform properties of polymers in GBs. The results reveal a significant deviation in the scaling behavior of brush height with σ compared to experimental data and theoretical predictions, and this deviation is attributed to the non-uniform Mn and D.
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Hypoxia is a critical factor for restricting photodynamic therapy (PDT) of tumor, and it becomes increasingly severe with increasing tissue depth. Thus, the relief of deep tumor hypoxia is extremely important to improve the PDT efficacy. Herein, tumor microenvironment (TME)-responsive size-switchable hyaluronic acid-hybridized Ru nanoaggregates (HA@Ru NAs) were developed via screening reaction temperature to alleviate deep tumor hypoxia for improving the tumor-specific PDT by the artful integration multiple bioactivated chemical reactions inâ situ and receptor-mediated targeting (RMT). In this nanosystem, Ru NPs not only enabled HA@Ru NAs to have near infrared (NIR)-mediated photothermal/photodynamic functions, but also could catalyze endogenous H2O2 to produce O2 inâ situ. More importantly, hyaluronidase (HAase) overexpressed in the TME could trigger disassembly of HA@Ru NAs via the hydrolysis of HA, offering the smart size switch capability from 60 to 15â nm for enhancing tumor penetration. Moreover, the RMT characteristics of HA ensured that HA@Ru NAs could specially enter CD44-overexpressed tumor cells, enhancing tumor-specific precision of phototherapy. Taken together these distinguishing characteristics, smart HA@Ru NAs successfully realized the relief of deep tumor hypoxia to improve the tumor-specific PDT.
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The study of cross-catenated metallacages, which are complex self-assembly systems arising from multiple supramolecular interactions and hierarchical assembly processes, is currently lacking but could provide facile insights into achieving more precise control over low-symmetry/high-complexity hierarchical assembly systems. Here, we report a cross-catenane formed between two position-isomeric Pt(II) metallacages in the solid state. These two metallacages formed [2]catenanes in solution, whereas a 1:1 mixture selectively formed a cross-catenane in crystals. Varied temperature nuclear magnetic resonance experiments and time-of-flight mass spectra are employed to characterize the cross-catenation in solutions, and the dynamic library of [2]catenanes are shown. Additionally, we searched for the global-minimum structures of three [2]catenanes and re-optimized the low-lying structures using density functional theory calculations. Our results suggest that the binding energy of cross-catenanes is significantly larger than that of self-catenanes within the dynamic library, and the selectivity in crystallization of cross-catenanes is thermodynamic. This study presents a cross-catenated assembly from different metallacages, which may provide a facile insight for the development of low-symmetry/high-complexity self-assemble systems.
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Dual-labeled single fluorescent probes are powerful tools for studying autophagy on the molecular scale, yet their development has been hampered by design complexity and a lack of valid strategies. Herein, for the first time, we introduce a combinatorial regulation strategy to fabricate dual-labeled probes for studying autophagy by integrating the specific organelle-targeting group and the functional fluorescence switch into a pentacyclic pyrylium scaffold (latent dual-target scaffold). For proof of concept, we prepared a range of dual-labeled probes (TMOs) that display different emission colors in duple organelles. In these probes, TMO1 and TMO2 enabled the simultaneous two-color visualization of the lysosomes and mitochondria. The other probes (TMO3 and TMO4) discriminatively targeted lysosomes/nucleolus and lysosomes/lipid droplets (LDs) with dual-color emission characteristics, respectively. Intriguingly, by simply connecting the endoplasmic reticulum (ER) targeting group to the pentacyclic pyrylium scaffold, we created the first dual-labeled probe TMO5 for simultaneously labeling lysosomes/ER in distinctive fluorescent colors. Subsequently, using the dual-labeled probe TMO2, drug-induced mitophagy was successfully recorded by evaluating the alterations of multiple mitophagy-related parameters, and the mitophagy defects in a cellular model of Parkinson's disease (PD) were also revealed by simultaneous dual-color/dual-organelle imaging. Further, the probe TMO4 can track the movement of lysosomes and LDs in real time and monitor the dynamic process of lipophagy. Therefore, this work not only presents attractive dual-labeled probes to promote the study of organelle interactions during autophagy but also provides a promising combinatorial regulation strategy that may be generalized for designing other dual-labeled probes with multiple organelle combinations.
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Colorantes Fluorescentes , Orgánulos , Colorantes Fluorescentes/metabolismo , Orgánulos/metabolismo , Lisosomas/metabolismo , Mitocondrias , Retículo Endoplásmico , AutofagiaRESUMEN
Owing to the strong Hg-Se interaction, Se-containing materials are promising for the uptake and immobilization of Hg(II) ions; compared with metal selenides or selenized compounds, elemental Se contains the highest ratio of Se. However, it remains a challenge to fully expose all the potential Se binding sites and achieve high utilization efficiency of elemental Se. Through rational design on the structure, dispersity, and size of materials, Se/CNF aerogels composed of abundant well-dispersed and amorphous nano-Se have been prepared and applied for the high-efficient uptake and immobilization of Hg(II) ions. The well-dispersion of nano-Se increases the exposure of Se sites, the amorphous structure benefits the easy cleavage of Se-Se bonds, the 3D porous networks of aerogels permit fast ions transport and easy operation. Benefiting from the combination effect of strong Hg-Se interaction and sufficient exposure of Se-enriched sites, the Se/CNF aerogels demonstrate strong binding ability (Kd = 3.8 ×105 mL·g-1), high capacity (943.4 mg·g-1), and preeminent selectivity (αMHg > 100) towards highly toxic Hg(II) ions. Notably, the utilization efficiency of Se in Se/CNF aerogels is as high as 99.5%. Moreover, the strong Hg-Se interaction and extraordinary stability of HgSe could minimize the environmental impact of the spent Se/CNF adsorbents after its disposal.
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Porphyrins and their derivatives are widely used as photosensitizers and sonosensitizers in tumor treatment. Nevertheless, their poor water solubility and low chemical stability reduce their singlet oxygen (1O2) yield and, consequently, their photodynamic therapy (PDT) and sonodynamic therapy (SDT) efficiency. Although strategies for porphyrin molecule assembly have been developed to augment 1O2 generation, there is scope for further improving PDT and SDT efficiencies. Herein, we synthesized ordered manganese porphyrin (SM) nanoparticles with well-defined self-assembled metalloporphyrin networks that enabled efficient energy transfer for enhanced photocatalytic and sonocatalytic activity in 1O2 production. Subsequently, Au nanoparticles were grown in situ on the SM surface by anchoring the terminal alkynyl of porphyrin to form plasmonic SMA heterostructures, which showed the excellent near-infrared-II (NIR-II) region absorption and photothermal properties, and facilitated electron-hole pair separation and transfer. With the modification of hyaluronic acid (HA), SMAH heterostructure nanocomposites exhibited good water solubility and were actively targeted to cancer cells. Under NIR-II light and ultrasound (US) irradiation, the SMAH generates hyperthermia, and a large amount of 1O2, inducing cancer cell damage. Both in vitro and in vivo studies confirmed that the SMAH nanocomposites effectively suppressed tumor growth by decreasing GSH levels in SDT-augmented PDT/PTT. Moreover, by utilizing the strong absorption in the NIR-II window, SMAH nanocomposites can achieve NIR-II photoacoustic imaging-guided combined cancer treatment. This work provides a paradigm for enhancing the 1O2 yield of metalloporphyrins to improve the synergistic therapeutic effect of SDT/PDT/PTT.
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Nanopartículas del Metal , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Fotoquimioterapia , Porfirinas , Humanos , Manganeso , Porfirinas/farmacología , Porfirinas/uso terapéutico , Oro/química , Nanopartículas del Metal/uso terapéutico , Nanopartículas del Metal/química , Fototerapia , Neoplasias/terapia , Agua , Línea Celular TumoralRESUMEN
The development of injectable self-healing adhesive hydrogel dressings with excellent bactericidal activity and wound healing ability is urgently in demand for combating biofilm infections. Herein, a multifunctional hydrogel (QP/QT-MB) with near-infrared (NIR) light-activated mild photothermal/gaseous antimicrobial activity was developed based on the dynamic reversible borate bonds and hydrogen bonds crosslinking between quaternization chitosan (QCS) derivatives alternatively containing phenylboronic acid and catechol-like moieties in conjunction with the in situ encapsulation of BNN6-loaded mesoporous polydopamine (MPDA@BNN6 NPs). Given the dynamic reversible cross-linking feature, the versatile hybrid hydrogel exhibited injectability, flexibility, and rapid self-healing ability. The numerous phenylboronic acid and catechol-like moieties on the QCS backbone confer the hydrogel with specific bacterial affinity, desirable tissue adhesion, and antioxidant stress ability that enhance bactericidal activity and facilitate the regeneration of infection wounds. Under NIR irradiation, the QP/QT-MB hydrogels exhibited a desirable mild photothermal effect and NIR-activity controllable NO delivery, combined with the endogenous contact antimicrobial activity of hydrogel, contributing jointly to induce dispersal of biofilms and disruption of the bacterial plasma membranes, ultimately leading to bacteria inactivation and biofilm elimination. In vivo experiments demonstrated that the fabricated QP/QT-MB hydrogel platform was capable of inducing efficient eradication of the S. aureus biofilm in a severely infected wound model and accelerating infected wound repair by promoting collagen deposition, angiogenesis, and suppressing inflammatory responses. Additionally, the QP/QT-MB hydrogel demonstrated excellent biocompatibility in vitro and in vivo. Collectively, the hydrogel (QP/QT-MB) reveals great potential application prospects as a promising alternative in the field of biofilm-associated infection treatment.
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Antiinfecciosos , Quitosano , Hidrogeles/farmacología , Preparaciones de Acción Retardada , Óxido Nítrico , Staphylococcus aureus , Cicatrización de Heridas , Biopelículas , CatecolesRESUMEN
Metal complexes have shown promise as photosensitizers for cancer diagnosis and therapeutics. However, the vast majority of metal photosensitizers are not ideal and associated with several limitations including pharmacokinetic limitations, off-target toxicity, fast systemic clearance, poor membrane permeability, and hypoxic tumour microenvironments. Metal complex functionalized nanomaterials have the potential to construct multifunctional systems, which not only overcome the above defects of metal complexes but are also conducive to modulating the tumour microenvironment (TME) and employing combination therapies to boost photodynamic therapy (PDT) efficacy. In this review, we first introduce the current challenges of photodynamic therapy and summarize the recent research strategies (such as metal coordination bonds, self-assembly, π-π stacking, physisorption, and so on) used for preparing metal complexes functionalized nanomaterials in the application of PDT.
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Complejos de Coordinación , Nanoestructuras , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Complejos de Coordinación/química , Nanoestructuras/química , Terapia Combinada , Neoplasias/patología , Microambiente TumoralRESUMEN
Bismuth sulfide is widely used as an n-type semiconductor material in photocatalytic reactions. However, bismuth sulfide has poor absorption in the near-infrared region and low charge separation efficiency, limiting its application in phototherapy and sonodynamic therapy (SDT). In this study, we successfully synthesized an "all-in-one" phototheranostic nanoplatform, namely Bi2S3-x-Au@HA, based on a single second near-infrared (NIR-II) light-responsive Schottky-type Bi2S3-x-Au heterostructure for photoacoustic (PA) imaging-guided SDT-enhanced photodynamic therapy (PDT)/photothermal therapy (PTT). Bi2S3-x-Au@HA exhibits excellent NIR-II plasmonic and photothermal properties, rendering it with NIR-II PA imaging capabilities for accurate diagnosis. Additionally, the high-density sulfur vacancies constructed on the Bi2S3 surface cause it to possess a reduced band gap (1.21 eV) that can act as an electron trap. Using the density functional theory, we confirmed that the light and ultrasound-induced electrons are more likely to aggregate on the Au nanoparticle surface through interfacial self-assembly, which promotes electron-hole separation and enhances photocatalytic activity with increased reactive oxygen species (ROS) generation. With a further modification of hyaluronic acid (HA), Bi2S3-x-Au@HA can selectively target cancer cells through HA and CD44 protein interactions. Both in vitro and in vivo experiments demonstrated that Bi2S3-x-Au@HA effectively suppressed tumor growth through SDT-enhanced PTT/PDT under a single NIR-II laser and ultrasound irradiation with negligible toxicity. Our findings provide a framework for fabricating Schottky-type heterostructures as single NIR-II light-responsive nanotheranostic agents for PA imaging-guided cancer phototherapy.
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Nanopartículas del Metal , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Fotoquimioterapia , Humanos , Técnicas Fotoacústicas/métodos , Oro/química , Nanopartículas del Metal/química , Fototerapia , Fotoquimioterapia/métodos , Nanopartículas/química , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Línea Celular TumoralRESUMEN
Increasing the reactive oxygen species (ROS) content at the tumor site is one of the effective strategies to promote intracellular oxidative stress and improve therapeutic efficiency. Herein, an atomically precise cinnamaldehyde-derived metal-organic Cu(I) complex (denoted as DC-OD-Cu) was rationally constructed. DC-OD-Cu could preferentially accumulate in the mitochondria of HeLa cells due to the mitochondria-targeting ability of triphenylphosphine, which was accompanied by the generation of large amounts of highly toxic hydroxyl radicals (ËOH) via Cu(I)-mediated Fenton-like reactions. Meanwhile, greater ROS generation jointly results in mitochondrial damage under white LED light irradiation. Furthermore, the in vitro and in vivo results suggested that DC-OD-Cu possesses favorable cytotoxicity and inhibits tumor growth. We believe that this research might provide a controllable strategy to construct multifunctional metal organic complexes for ROS-involved CDT.
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Complejos de Coordinación , Humanos , Células HeLa , Especies Reactivas de Oxígeno , Complejos de Coordinación/farmacología , Luz , Mitocondrias , Línea Celular Tumoral , Peróxido de HidrógenoRESUMEN
Chemodynamic immunotherapy that utilizes catalysts to produce reactive oxygen species (ROS) for killing tumor cells and arousing antitumor immunity has received considerable attention. However, it is still restricted by low ROS production efficiency and insufficient immune activation, due to intricate redox homeostasis in the tumor microenvironment (TME). Herein, a metalloprotein-like hybrid nanozyme (FeS@GOx) is designed by in situ growth of nanozyme (ferrous sulfide, FeS) in a natural enzyme (glucose oxidase, GOx) to amplify ROS cascade for boosting chemodynamic immunotherapy. In FeS@GOx, GOx allows the conversion of endogenous glucose to gluconic acid and hydrogen peroxide, which provides favorable increasing hydrogen peroxide for subsequent Fenton reaction of FeS nanozymes, thus reinforcing ROS production. Notably, hydrogen sulfide (H2 S) release is activated by the gluconic acid generation-related pH decrease, which can suppress the activity of endogenous thioredoxin reductase and catalase to further inhibit ROS elimination. Thus, FeS@GOx can sustainably amplify ROS accumulation and perturb intracellular redox homeostasis to improve chemodynamic therapy and trigger robust immunogenic cell death for effective immunotherapy combined with immune checkpoint blockade. This work proposes a feasible H2 S amplified ROS cascade strategy employing a bioinspired hybrid nanozyme, providing a novel pathway to multi-enzyme-mediated TME modulation for precise and efficient chemodynamic immunotherapy.
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Peróxido de Hidrógeno , Sulfuro de Hidrógeno , Sulfuro de Hidrógeno/farmacología , Especies Reactivas de Oxígeno , Inmunoterapia , Microambiente TumoralRESUMEN
Zn2+ and H2S are essential to maintain normal prostate function, and sometimes can evolve into weapons to attack and destroy prostate cancer (PCa) cells. Nevertheless, how to achieve the targeted and effective release of Zn2+ and H2S, and reverse the concentration distribution within PCa tumor cells still highly challenging. Herein, combined with these pathological characteristics of prostate, we proposed a tumor microenvironment (TME) responsive Zn2+-interference and H2S-mediated gas synergistic therapy strategy based on a nanoplatform of tannic acid (TA) modified zinc sulfide nanoparticles (ZnS@TA) for the specific treatment of PCa. Once the constructed pH-responsive ZnS@TA internalized by cancer cells, it would instantaneously decomposed in acidic TME, and explosively release excess Zn2+ and H2S exceeding the cell self-regulation threshold. Meanwhile, the in situ produced Zn2+ and H2S synergistic enhancement of cell apoptosis, which is evidenced to increase levels of Bax and Bax/Bcl-2 ratio, release of Cytochrome c in cancer cells, contributing to inhibit the growth of tumor. Moreover, the TA in cooperation with Zn2+ specifically limits the migration and invasion of PCa cells. Both in vitro and in vivo results demonstrate that the Zn2+-interference in combination with H2S-mediated gas therapy achieves an excellent anti-tumor performance. Overall, this nanotheranostic synergistic therapy provides a promising direction for exploring new strategies for cancer treatment based on specific tumor pathological characteristics, and provides a new vision for promoting practical cancer therapy.
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Nanopartículas , Neoplasias de la Próstata , Masculino , Humanos , Proteína X Asociada a bcl-2 , Apoptosis , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Zinc/farmacología , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Using solar energy to drive catalytic conversion of CO2 into value-added chemicals has great potential to alleviate the global energy shortage and anthropogenic climate change. Herein, a "hitting three birds with one stone" strategy was reported to prepared boron-doped g-C3N4/TiO2-x composite (BCT) by a one-step thermal reduction process. A series of characterizations showed that the composite catalyst has extended full-spectrum absorption, rapid photogenerated charge separation, and outstanding CO2 photoreduction performance (265.2 µmol g-1h-1), which is 7.5 and 9.2 times higher than that of pure TiO2 and g-C3N4, respectively. In addition, the CO2 conversion rate can be further increased to 345.1 µmol g-1h-1 at 70 °C due to its excellent photothermal conversion. Mechanistic studies reveal that synergistic effects alter the charge density distribution, thereby lowering the energy barrier for CO2 conversion by adsorbing and activating CO2 molecules. This work provides a novel three-in-one integrated strategy for fabricating high-efficiency catalysts.
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Dióxido de Carbono , Energía Solar , Luz , CatálisisRESUMEN
Phototheranostics has attracted considerable attention in the fields of cancer diagnosis and treatment. However, the complete eradication of solid tumors using traditional phototheranostics is difficult because of the limited depth and range of laser irradiation. New phototheranostics enabling precise phototherapy and post-treatment imaging-guided programmed therapy for residual tumors is urgently required. Accordingly, this study developed a novel transformable phototheranostics by assembling hyaluronic acid (HA) with copper-nitrogen-coordinated carbon dots (CDs). In this transformable nanoplatform, named copper-nitrogen-CDs@HA, the HA component enables the specific targeting of cluster determinant (CD) 44-overexpressing tumor cells. In the tumor cells, redox glutathione converts Cu(II) (cupric ions) into Cu(I) (cuprous ions), which confers the novel transformable functionality to phototheranostics. Both in vitro and in vivo results reveal that the near-infrared-light-photoactivated CuII-N-CDs@HA could target CD44-overexpressing tumor cells for precise synergistic photothermal therapy and photodynamic therapy. This study is the first to observe that CuII-N-CDs@HA could escape from lysosomes and be transformed in situ into CuI-N-CDs@HA in tumor cells, with the d9 electronic configuration of Cu(II) changing to the d10 electronic configuration of Cu(I), which turns on their fluorescence and turns off their photothermal properties. This transformable phototheranostics could be used for post-treatment imaging-guided photodynamic therapy on residual tumor cells. Thus, the rationally designed copper-nitrogen-coordinated CDs offer a simple in situ transformation strategy for using multiple-stimulus-responsive precise phototheranostics in post-treatment monitoring of residual tumor cells and imaging-guided programmed therapy.
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Nanopartículas , Fotoquimioterapia , Humanos , Carbono/química , Carbono/farmacología , Línea Celular Tumoral , Cobre/química , Cobre/farmacología , Nanopartículas/uso terapéutico , Neoplasia Residual/tratamiento farmacológico , Fotoquimioterapia/métodos , Fototerapia , Nitrógeno/química , Nitrógeno/farmacologíaRESUMEN
Natural biopolymers can be controllably in situ synthesized in organisms and play important roles in biological activities. Inspired by this, the manipulation of in situ biosynthesis of functional polymers in vivo will be an important way to obtain materials for meeting biological requirements. Herein, in situ biosynthesis of functional conjugated polymer at the tumor site was achieved via the utilization of specific tumor microenvironment (TME) characteristics for the first time. Specially, a water-soluble aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) nanoparticles at the tumor site, which was activated via the catalysis of hydrogen peroxide (H2O2) overexpressed in TME to produce hydroxyl radical (â¢OH) by coinjected horseradish peroxidase (HRP). Benefiting from outstanding near-infrared (NIR)-II absorption of PSPA, the in situ polymerization process can be validly monitored by photoacoustic (PA) signal at the NIR-II region. Meanwhile, in situ polymerization would induce the size of polymeric materials from small to large, improving the distribution and retention of PSPA at the tumor site. On the combination of NIR-II absorption of PSPA and the size variation induced by polymerization, such polymerization can be applied for tumor-specific NIR-II light mediated PA image and photothermal inhibition of tumors, enhancing the precision and efficacy of tumor phototheranostics. Therefore, the present work opens the way to manipulate TME-activated in situ biosynthesis of functional conjugated polymer at the tumor site for overcoming formidable challenges in tumor theranostics.
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Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Polimerizacion , Peróxido de Hidrógeno , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Polímeros , Compuestos de Anilina , Línea Celular Tumoral , Nanomedicina Teranóstica/métodos , Fototerapia/métodos , Técnicas Fotoacústicas/métodos , Microambiente TumoralRESUMEN
As promising photonic material, phototheranostics can be activated in the laser irradiation range of tumor with sensitivity and spatiotemporal precision. However, it is difficult to completely eradicate solid tumors due to their irregularity and limited laser irradiation area. Herein, multi-stimulus responsive HA-Ce6@SWNHs were constructed with single-walled carbon nanohorns (SWNHs) and chlorine e6 (Ce6) modified hyaluronic acid (HA) via non-covalent binding. This SWNHs-based phototheranostics not only exhibited water dispersion but also could target tumor and be activated by near-infrared light for photodynamic therapy (PDT) and photothermal therapy (PTT). Additionally, HA-Ce6@SWNHs could be degraded by hyaluronidase in residual tumor cells, causing HA-Ce6 to fall off the SWNHs surfaces to restore autofluorescence, thus precisely guiding the programmed photodynamic treatments for residual tumor cells after the initial phototherapy. Thus, this work provides a rationally designed multiple-stimulus-response strategy to develop smart SWNHs-based phototheranostics for precise PDT/PTT and post-treatment imaging-guided PDT of residual tumor cells.