Supramolecular Chiral Binding Affinity-Achieved Efficient Synergistic Cancer Therapy.

Supramolecular chirality-mediated selective interaction among native assemblies is essential for precise disease diagnosis and treatment. Herein, to fully understand the supramolecular chiral binding affinity-achieved therapeutic efficiency, supramolecular chiral nanoparticles (WP5⊃D/L-Arg+DOX+ICG) with the chirality transfer from chiral arginine (D/L-Arg) to water-soluble pillar[5]arene (WP5) are developed through non-covalent interactions, in which an anticancer drug (DOX, doxorubicin hydrochloride) and a photothermal agent (ICG, indocyanine green) are successfully loaded. Interestingly, the WP5⊃D-Arg nanoparticles show 107 folds stronger binding capability toward phospholipid-composed liposomes compared with WP5⊃L-Arg. The enantioselective interaction further triggers the supramolecular chirality-specific drug accumulation in cancer cells. As a consequence, WP5⊃D-Arg+DOX+ICG exhibits extremely enhanced chemo-photothermal synergistic therapeutic efficacy (tumor inhibition rate of 99.4%) than that of WP5⊃L-Arg+DOX+ICG (tumor inhibition rate of 56.4%) under the same condition. This work reveals the breakthrough that supramolecular chiral assemblies can induce surprisingly large difference in cancer therapy, providing strong support for the significance of supramolecular chirality in bio-application.

Exploring Immune-Related Gene Profiling and Infiltration of Immune Cells in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.

Cervical cancer is a widespread malignancy among women, leading to a substantial global health impact. Despite extensive research, our understanding of the basic molecules and pathogenic processes of cervical squamous cell carcinoma is still insufficient. This investigation aims to uncover immune-related genes linked to CESC and delineate their functions. Leveraging data from the GEO and ImmPort databases, a total of 22 immune-related genes were identified. Multiple tools, including DAVID, the human protein atlas, STRING, GeneMANIA, and TCGA, were employed to delve into the expression and roles of these immune genes in CESC, alongside their connections to the disease's pathological features. Through RT-PCR, the study confirmed notable disparities in CXCL8 and CXCL10 mRNA expression between CESC and normal cervical tissue. The TCGA dataset's immune-related information reinforced the association of CXCL8 and CXCL10 with immune infiltration in CESC. This research sheds light on the potential of CXCL8 and CXCL10 as promising therapeutic targets and essential prognostic factors for individuals diagnosed with CESC.

Shape-Regulated Photothermal-Catalytic Tumor Therapy Using Polydopamine@Pt Nanozymes with the Elicitation of an Immune Response.

Recently, nanozyme-based photothermal-catalytic therapy has emerged as a promising strategy for antitumor treatment. Extensive research has focused on optimizing the catalytic activity and photothermal conversion performance of nanozymes through size, morphology, and surface property regulations. However, the biological effects of nanozymes, such as cellular uptake and cytotoxicity, resulting from their physicochemical properties, remain largely unexplored. In this study, two types of polydopamine/platinum (PDA@Pt) nanozymes, flower-like (FPDA@Pt) and mesoporous spherical-like (MPDA@Pt), to comprehensively compare their enzyme-mimicking activity, photothermal conversion capacity, and antitumor efficiency are designed. These findings revealed that FPDA@Pt exhibited superior peroxidase-like activity and higher photothermal conversion efficiency compared to MPDA@Pt. This led to enhanced production of reactive oxygen species (ROS) and increased heat generation at tumor sites. Importantly, it is observed thatthe flower-like structure of FPDA@Pt facilitated enhanced cellular uptake, leading to an increased accumulation of nanozymes within tumor cells. Furthermore, the light irradiation on tumors also triggered a series of anti-tumor immune responses, further enhancing the therapeutic efficacy. This work provides a possible design orientation for nanozyme-based photothermal-catalytic tumor therapy, highlighting the importance of considering the physicochemical properties of nanozymes to optimize their therapeutic potential in antitumor strategies.

Biomineralized Polydopamine Nanoparticle-Based Sodium Alginate Hydrogels for Delivery of Anti-serine/Threonine Protein Kinase B-Rapidly Accelerated Fibrosarcoma siRNA for Metastatic Melanoma Therapy.

Malignant melanoma, as a highly aggressive skin cancer, is strongly associated with mutations in serine/threonine protein kinase B-RAF (BRAF, where RAF stands for rapidly accelerated fibrosarcoma). Targeted therapy with anti-BRAF small interfering RNA (siBRAF) represents a crucial aspect of metastatic melanoma treatment. In this study, an injectable hydrogel platform based on sodium alginate (SA), with multifunctions of photothermal and Ca2+-overload cell apoptosis, was explored as a siBRAF carrier for metastatic melanoma therapy. We employed polydopamine nanoparticles (PDAs) as a photothermal core and constructed a calcium phosphate (CaP) shell via biomineralization (PDA@CaP) to load siBRAF (PDA@siBRAF/CaP). The pH-sensitive CaP shell facilitated the release of Ca2+ under the weakly acidic tumor microenvironment, triggering the gelation of PDA@siBRAF/CaP-SA to localized release siBRAF at tumor sites with the interruption of the RAS-RAF-MEK-ERK (MAPK) pathway. Besides, the continuous release of Ca2+ could also lead to Ca2+-overload cell apoptosis. Moreover, the photothermal effect of PDA regulated the release kinetics, resulting in coordinated therapeutic abilities of individual components in the PDA@siBRAF/CaP-SA hydrogels. Consequently, the effective inhibition of tumor growth and metastasis was achieved in vitro and in vivo using a highly metastatic melanoma cell line B16F10 as the model, by combining photothermal ablation, Ca2+ overload, and BRAF silencing. Our work provides a proof-of-concept for an injectable hydrogel system that simultaneously targets multiple mechanisms involved in melanoma progression and has the potential to be translated into clinical use for the metastatic melanoma therapy.

CaCO3-assistant synthesis of pH/near-infrared light-responsive and injectable sodium alginate hydrogels for melanoma synergistic treatment.

Melanoma is an aggressive tumor located in skin with high rates of recurrence and metastasis. Due to the limited traditional therapies, the development of novel strategies against melanoma is urgently quested. To reduce the side effects of traditional administration ways and amplify the killing effect, an injectable sodium alginate (SA)-based hydrogels were developed, in which CaCO3/polydopamine nanoparticles (CaCO3/PDA NPs) were embedded for the synergistic photothermal/calcium ions interference therapy of melanoma. In the study, the formation conditions and mechanical properties of CaCO3/PDA-SA hydrogels were characterized, and their antitumor efficiency and mechanism against mouse melanoma cells were investigated. Wheninjectedintratumorally, CaCO3/PDA-SA fluid was converted into hydrogel in situ through the interaction of pH-sensitive released Ca2+ and alginate chains, which increased the retention time of photothermal agents (CaCO3/PDA NPs) at tumor sites and thereby was more conducive to produce hyperthermia via photothermal conversion to combat melanoma. Moreover, in acidic tumor microenvironment, the residual CaCO3/PDA NPs in hydrogels continuously decomposed and released Ca2+ to destroy the Ca2+ buffering capacity and evoke the mitochondrial Ca2+-overloading, resulting in the inhibition of adenosine triphosphate production to accelerate cell death. Notably, besides the heat elevation, the near-infrared light (NIR) irradiation would further enhance the release of Ca2+ to promote the Ca2+-involved cell death. Therefore, a pH/NIR-responsive and injectable SA-based hydrogels were successfully established and showed enhanced treatment efficacy of melanoma through the synergism of photothermal therapy and calcium ions interference therapy.

Ferrous iron-induced formation of glycyrrhizic acid hydrogels for Staphylococcus aureus-infected wound healing.

Severe skin wound healing is mainly hindered by bacterial infection and uncontrolled inflammatory reaction. As a wound dressing, multifunctional hydrogel is expected to offer the potential possibility for overcoming current barriers in wound therapeutics. Herein, a natural drug molecule (glycyrrhizic acid, GA) and metal ion (Fe2+) were used to achieve the metal coordination-induced gelation. This as-prepared Fe2+-induced GA hydrogel showed excellent injectability, self-healing property, and sustained release behavior at a relatively lower concentration of GA, thereby reducing the high dose-caused cytotoxicity. In addition to acting as an inducer of gelation, Fe2+ promoted the antibacterial performance of hydrogel against Escherichia coli and Staphylococcus aureus through causing lipid peroxidation, membrane damage, and DNA degradation. Moreover, the released GA from hydrogel significantly accelerated cell migration and inhibited the inflammatory reaction by mediation of NF-κB signaling pathway to downregulate levels of important inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells. Using a mouse skin infected model, we revealed that the Fe2+/GA hydrogel applied to the wound resulted in the rapid wound healing. It is believed that the construction of natural drug molecule-derived hydrogel with antibacterial and anti-inflammatory capabilities may shed a new light to serve as a promising dressing for managing the severe skin wounds.

Biomedical applications of iron sulfide-based nanozymes.

Nanozymes have attracted great interest owing to their marvelous advantages, such as high stability, facile preparation, and high tunability. In particular, iron sulfide-based nanozymes (termed as ISNs), as one of the most researched nanomaterials with versatile enzyme-mimicking properties, have proved their potential in biomedical applications. In this review, we briefly summarize the classification, catalytic mechanisms of ISNs and then principally introduce ISNs' biomedical applications in biosensors, tumor therapy, antibacterial therapy, and others, demonstrating that ISNs have promising potential for alleviating human health.

Yolk-shell Fe3O4@Carbon@Platinum-Chlorin e6 nanozyme for MRI-assisted synergistic catalytic-photodynamic-photothermal tumor therapy.

HYPOTHESIS: Tumor treatments based on phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), are promising anticancer strategies. However, their dependence on light also poses several limitations for their application. Therefore, the establishment of a multifunctional nanotheranostic platform based on light therapy is needed to improve applicability of the technology. EXPERIMENTS: We designed yolk-shell magnetic Fe3O4@Carbon@Platinum-Chlorin e6 nanoparticles (MCPtCe6), which may be used for Magnetic resonance imaging (MRI) and synergistic catalytic-photodynamic-photothermal (catalytic-PDT-PTT) tumor therapy. FINDINGS: We designed to compound multiple nanozymes and solve the drawbacks of single nanozyme and give additional functionalization to nanozymes for tumor therapy. Fe3O4 has T2 weighted MRI ability. The designed yolk-shell structure can disperse Fe3O4 in the carbon shell layer, which in turn can act as a carrier for PtNPs and improve the dispersion of both Fe3O4 and Pt. Pt nanoparticles attached to the surface of N-doped carbon spheres enhanced the catalytic ability of the nanozyme to generate reactive oxygen species (ROS). The covalently linked photosensitizer chlorin e6 (Ce6) on the Fe3O4@C@Pt (MCPt) nanozyme is essential for the therapeutic effects of PDT. MCPtCe6 can be specifically activated by the microenvironment through an enzyme-like catalytic process and extend PDT/PTT in acidic and H2O2-rich microenvironments. The results showed that MCPtCe6 had a high photothermal conversion efficiency (η = 28.28%), indicating its feasibility for PTT. Further cellular and animal studies have revealed that catalytic-PDT-PTT therapy can effectively inhibit tumors both in vitro and in vivo.

Construction of core-in-shell Au@N-HCNs nanozymes for tumor therapy.

Noble metals act as nanozymes that can generate reactive oxygen species (ROS) by catalysis to induce apoptosis of tumor cells for cancer therapy. But they are easy to aggregate, which will affect their further application. Carbon materials are often used as the carrier of noble metals to improve their catalytic performance. However, designing a composite structure to build an efficient carbon/noble metal hybrid nanozyme with high catalytic performance for tumor therapy is still a significant challenge. In this work, a core-in-shell structure nanozyme composed of gold nanoparticles (AuNPs) embedded in nitrogen-doped hollow carbon nanoshells (AuNPs@N-HCNs) were fabricated, which exhibited peroxidase-like (POD-like) and oxidase-like (OXD-like) activity. Compared with core-out-of-shell structure composite, the AuNPs@N-HCNs showed a better ability to generate ROS to kill tumor cells. Furthermore, AuNPs@N-HCNs also exhibited satisfactory photothermal conversion properties, which helped build a platform for photothermal therapy. Meanwhile, the enzyme activity produced by AuNPs@N-HCNs increased significantly under light irradiation. Comparing the size of AuNPs in carbon shell, 15 nm AuNPs were better than 2 nm in both enzyme-like activities and in vivo therapeutic effect. In vitro and in vivo studies demonstrated that under the synergistic effect of light-enhancing nanozyme catalysis and photothermal therapy, AuNPs@N-HCNs could induce cancer cell apoptosis and destroy tumors effectively, which provided evidence for the feasibility of tumor catalytic-photothermal treatment.

Metal ions/nucleotide coordinated nanoparticles comprehensively suppress tumor by synergizing ferroptosis with energy metabolism interference.

BACKGROUND: Ferroptosis holds promise as a potential tumor therapy by programming cell death with a hallmark of reactive oxygen species (ROS)-induced lipid peroxidation. However, vigorous energy metabolism may assist tumors to resist oxidative damage and thus weaken the effects of ferroptosis in tumor treatment. RESULTS: Herein, a bifunctional antitumor platform was constructed via coordinated interactions between metal ions and nucleotides to synergistically activate ferroptosis and interrupt energy metabolism for tumor therapy. The designed nanoparticles were composed of Fe2+/small interfering RNA (siRNA) as the core and polydopamine as the cloak, which responded to the tumor microenvironment with structural dissociation, thereby permitting tumor-specific Fe2+ and siRNA release. The over-loaded Fe2+ ions in the tumor cells then triggered ferroptosis, with hallmarks of lipid peroxidation and cellular glutathione peroxidase 4 (GPX4) down-regulation. Simultaneously, the released siRNA targeted and down-regulated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression in the tumor to inhibit glycolytic pathway, which interfered with tumor energy metabolism and enhanced Fe2+-induced ferroptosis to kill tumor cells. CONCLUSIONS: This study presents a concise fabrication of a metal ion/nucleotide-based platform to integrate ferroptosis and energy metabolism intervention in one vehicle, thereby providing a promising combination modality for anticancer therapy.

Supramolecular Core-Shell Nanoassemblies with Tumor Microenvironment-Triggered Size and Structure Switch for Improved Photothermal Therapy.

Photothermal therapy (PTT) is demonstrated to be an effective methodology for cancer treatment. However, the relatively low photothermal conversion efficiency, limited tumor accumulation, and penetration still remain to be challenging issues that hinder the clinical application of PTT. Herein, the core-shell hierarchical nanostructures induced by host-guest interaction between water-soluble pillar[5]arene (WP5) and polyethylene glycol-modified aniline tetramer (TAPEG) are constructed. The pH-responsive performance endows the core-shell nanostructures with size switchable property, with an average diameter of 200 nm in the neutral pH and 60 nm in the acidic microenvironment, which facilitates not only tumor accumulation but also tumor penetration. Moreover, the structure switch of WP5⊃TAPEG under acidic microenvironment and the dual mechanism regulated extending of п conjugate, inclusion in the hydrophobic cavity of WP5 and the dense distribution in the core-shell structured assemblies, dramatically enhance the absorption in the near-infrared-II region and, further, the photothermal conversion efficiency (60.2%). The as-designed intelligent nanoplatform is demonstrated for improved antitumor efficacy via PTT.

Staphylococcus aureus-targeting peptide/surfactant assemblies for antibacterial therapy.

To address the challenge from microbial resistance, this work developed a surfactant with 18-carbon single hydrocarbon chain and multi-amine head groups (C18N3). After assembling with Staphylococcus aureus-targeting peptide (CARG), the obtained C18N3/CARG assemblies exhibited excellent antimicrobial activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in vitro and in vivo, in which the targeting peptide CARG bonded specifically to Staphylococcus aureus and C18N3 killed bacteria with a mechanism of membrane disruption. Importantly, C18N3 could also work as a ß-lactamase inhibitor to overcome the bacterial resistance to ß-lactam antibiotics through noncompetitive inhibition. The combination of ß-lactam antibiotic and C18N3/CARG assemblies more effectively suppressed methicillin-resistant Staphylococcus aureus in vitro and in vivo relative to equivalent dose of free antibiotic or C18N3. Thus, the antibacterial platform of antibiotic-carrying surfactant assemblies bearing bacteria-targeted peptides, in which C18N3 performed dual function, antibacterial agent and ß-lactamase inhibitor, may help fight against the difficult-to-treat infections.

Gold nanorod@void@polypyrrole yolk@shell nanostructures: Synchronous regulation of photothermal and drug delivery performance for synergistic cancer therapy.

Synergistic therapy has been emerging as new trend for effective tumor treatment due to synchronous function and cooperative reinforcement of multi therapeutic modalities. Herein, gold nanorods (GNRs) encapsulated into polypyrrole (PPy) shell with tunable void space (GNRs@Void@PPy) showing yolk@shell nanostructures were innovatively designed. The exploitation of dual near-infrared (NIR) absorptive species offered synergistic enhancement of photothermal performance. In addition, the manipulation of the void space between them provided additional benefits of high drug encapsulation efficiency (92.6%) and, interestingly, tumor microenvironment and NIR irradiation triggered targeted drug releasing. Moreover, the GNRs@Void@PPy exhibited excellent biocompatibility, and optimal curative effect by chemo-photothermal synergistic therapy was achieved through both in vitro and in vivo antitumor activity investigation.

Artesunate-loaded poly (lactic-co-glycolic acid)/polydopamine-manganese oxides nanoparticles as an oxidase mimic for tumor chemo-catalytic therapy.

Conventional tumor chemotherapy is limited by its low therapeutic efficacy and side effects, which severely hold back its further application as a first-line agent in clinic. To improve the cure efficacy of cancer, nanozyme with enzyme-like activity has now been extensively investigated as a new strategy for tumor treatment. Herein, an anti-tumor platform based on manganese oxides (MnOx) modified poly (lactic-co-glycolic acid) (PLGA)@polydopamine (PDA) nanoparticles (PP-MnOx NPs) as an oxidase mimic was developed. PP-MnOx NPs could not only produce abundant reactive oxygen species to inhibit tumor growth taking advantage of their oxidase-like activity, but also encapsulate and release antitumor drug (artesunate) to function as chemotherapy, achieving remarkable synergistic chemo-catalytic therapeutic effects. As an oxidase mimics, PP-MnOx NPs induced the decrease of mitochondrial membrane potential, down-regulation of Bcl-2, as well as activation of Bax and Caspase-3, demonstrating that the apoptosis triggered by PP-MnOx NPs was mediated via mitochondrial pathways. Importantly, the artesunate in PP-MnOx NPs further promoted this apoptosis. In addition, Mn ions released from PP-MnOx NPs facilitated the tumor-microenvironment-specific T1-weighted magnetic resonance imaging. Taken together, this study well clarifies the antitumor mechanism of artesunate-loaded PP-MnOx NPs and offer a synergistic chemo-catalytic strategy for tumor theranostics.

Catalytic inactivation of influenza virus by iron oxide nanozyme.

Influenza poses a severe threat to human health in the world. However, developing a universal anti-viral strategy has remained challenging due to the presence of diverse subtypes as well as its high mutation rate, resulting in antigenic shift and drift. Here we developed an antiviral strategy using iron oxide nanozymes (IONzymes) to target the lipid envelope of the influenza virus. Methods: We evaluated the antiviral activities of our IONzymes using a hemagglutination assay, together with a 50% tissue culture infectious doses (TCID50) method. Lipid peroxidation of the viral envelope was analyzed using a maleic dialdehyde (MDA) assay and transmission electron microscopy (TEM). The neighboring viral proteins were detected by western blotting. Results: We show that IONzymes induce envelope lipid peroxidation and destroy the integrity of neighboring proteins, including hemagglutinin, neuraminidase, and matrix protein 1, causing the inactivation of influenza A viruses (IAVs). Furthermore, we show that our IONzymes possess a broad-spectrum antiviral activity on 12 subtypes of IAVs (H1~H12). Lastly, we demonstrate that applying IONzymes to a facemask improves the ability of virus protection against 3 important subtypes that pose a threat to human, including H1N1, H5N1, and H7N9 subtype. Conclusion: Together, our results clearly demonstrate that IONzymes can catalyze lipid peroxidation of the viral lipid envelope to inactivate enveloped viruses and provide protection from viral transmission and infection.

Light-enhanced sponge-like carbon nanozyme used for synergetic antibacterial therapy.

Bacterial infection and the issue of antibiotic resistance have become one of the major public health problems worldwide. Thus, searching for new antibacterial agents is urgently required. Hydrogen peroxide, H2O2, as a traditional bactericide, is applied widely for medical treatments. However, the relatively high concentration of H2O2 used in a clinical setting usually inhibits wound healing and even damages normal tissues during disinfection. Here, we synthesized N-doped sponge-like carbon spheres (N-SCSs), which showed excellent mimicking activities for multiple enzymes, including peroxidase, oxidase, superoxide dismutase, and catalase. We then utilized the peroxidase-like activity of the N-SCSs to convert low-concentration H2O2 into radical oxygen species to resist bacteria. The data showed that the antibacterial performance of H2O2 against Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus aureus), and multidrug-resistant bacteria was improved through the peroxidase-like catalytic reaction of N-SCSs. Importantly, besides generating heat against bacteria, near-infrared laser exposure also promoted the peroxidase activity of N-SCSs, to further generate radical oxygen species to kill bacteria. In addition, this catalytic-photothermal antibacterial strategy demonstrated accelerated recovery of infected wounds in an animal model. Thus, our work provides a new synergetic anti-infection strategy, and further expands the application of carbon-based nanozymes in biomedicine.

NKG2D-IL-15 fusion protein encapsulated in N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride retards melanoma growth in mice.

BACKGROUND: Chitosan can be modified to increase the efficiency of the delivery of chemical drugs, nucleic acids, or proteins. Sodium tripolyphosphate (TPP) is a noncytotoxic and polyanionic crosslinker that binds with the positively charged ions of chitosan. DsNKG2D-IL-15 is a fusion protein that exerts promising antitumor effects via lymphocyte activation. The extracellular domains of double NKG2D is linked to IL-15. METHODS: To increase the stability and efficiency of dsNKG2D-IL-15 protein, the fusion protein was encapsulated in nanoparticles based on chitosan pre-modified with N-(2-hydroxy) propyl-3-trimethyl ammonium (HTCC). Moreover, the biological activity of protein nanoparticle was evaluated on the mouse lymphocyte ex vivo and mouse tumor model in vivo. RESULTS: TPP sharply promoted the HTCC chitosan encapsulating efficiency (85-95%) with dsNKG2D-IL-15. The protein nanoparticle displayed a spherical shape with a diameter of 200-400 nm and zeta-potential value of 15.6±4.82 mV. DsNKG2D-IL-15 could be released from the nanogel within 72 h. In addition, the protein biological activity for lymphocyte activation was maintained. Natural killer (NK) and CD8+ T cells increased the activity of IFN-γ production and degranulation after incubation with the dsNKG2D-IL-15-HTCC-TPP nanoparticle ex vivo. Treatment with dsNKG2D-IL-15 nanoparticles exhibited better effects of inhibiting tumor growth and prolonging the life span of B16BL6-MICA tumor-bearing mice in vivo than by using the dsNKG2D-IL-15 protein alone. CONCLUSIONS: The dsNKG2D-IL-15 protein nanoparticle exhibited notable effects of lymphocyte activation and tumor inhibition. The protein nanoparticle could be developed further for tumor therapy in clinical practice.

Gold Nanorods/Polypyrrole/m-SiO2 Core/Shell Hybrids as Drug Nanocarriers for Efficient Chemo-Photothermal Therapy.

Combination therapy as a novel strategy with the combination of photothermal therapy and chemotherapy (photothermal-chemotherapy) has aroused the tremendously increasing interest owing to the synergistic therapeutic effect on destroying cancer cells because the hyperthermia generated from photothermal therapy can promote drug delivery into tumors, which would highly increase therapeutic efficacy as compared to those sole treatments. Herein, we fabricated a novel nanomaterial-based carrier composed of gold nanorods (GNRs), polypyrrole (PPy), and mesoporous silica to form GNRs/PPy/m-SiO2 core/shell hybrids. After loading the anticancer drug of doxorubicin (DOX), the photothermal effect and the drug-release behavior of GNRs/PPy@m-SiO2-DOX hybrids were investigated. The in vitro and in vivo near-infrared (NIR) photothermal-chemotherapy were also revealed. The results indicated that the NIR-induced photothermal effect was beneficial to promote the release of the drug. In addition, combination therapy demonstrated the enhanced synergistic efficacy and excellent treatment efficacy for cancer therapy.

In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy.

Nanomaterials with intrinsic enzyme-like activities (nanozymes), have been widely used as artificial enzymes in biomedicine. However, how to control their in vivo performance in a target cell is still challenging. Here we report a strategy to coordinate nanozymes to target tumor cells and selectively perform their activity to destruct tumors. We develop a nanozyme using nitrogen-doped porous carbon nanospheres which possess four enzyme-like activities (oxidase, peroxidase, catalase and superoxide dismutase) responsible for reactive oxygen species regulation. We then introduce ferritin to guide nitrogen-doped porous carbon nanospheres into lysosomes and boost reactive oxygen species generation in a tumor-specific manner, resulting in significant tumor regression in human tumor xenograft mice models. Together, our study provides evidence that nitrogen-doped porous carbon nanospheres are powerful nanozymes capable of regulating intracellular reactive oxygen species, and ferritinylation is a promising strategy to render nanozymes to target tumor cells for in vivo tumor catalytic therapy.

Controllable Synthesis of Gold Nanorod/Conducting Polymer Core/Shell Hybrids Toward in Vitro and in Vivo near-Infrared Photothermal Therapy.

Photothermal therapy (PTT) is a minimally invasive tumor treatment technology, and is regarded as a potential anticancer strategy because of its targeted destruction and low toxicity. Specifically, near-infrared light-induced PTT has attracted intriguing interest because of the high transparency of tissue, blood, and water. However, effective PTT generally requires the assistance of photothermal agents. Gold nanorods (GNRs) and conducting polymer are often used as photothermal materials because of their high absorption efficiency and photothermal conversion efficiency. Herein, we combined GNRs with poly( o-methoxyaniline) (POMA, a polyaniline derivative) to form GNRs/POMA core/shell hybrids through the surfactant-assisted chemical oxidative polymerization route and studied their photothermal conversion properties. The configuration of GNRs/POMA core/shell hybrids has been precisely controlled through adjusting the monomer concentration, and the relationship between morphology and absorption band of GNRs/POMA core/shell hybrids has been revealed. Finally, the in vitro and in vivo experiments were performed, and the results indicated that the GNRs/POMA core/shell hybrids with optimized absorbance at around 808 nm exhibited the best performance on photothermal therapy under 808 nm NIR laser irradiation.