Crystal Facet Controlled Metal-Support Interaction in Uricase Mimics for Highly Efficient Hyperuricemia Treatment.

The effect of strong metal-support interaction (SMSI) has never been systematically studied in the field of nanozyme-based catalysis before. Herein, by coupling two different Pd crystal facets with MnO2, i.e., (100) by Pd cube (Pdc) and (111) by Pd icosahedron (Pdi), we observed the reconstruction of Pd atomic structure within the Pd-MnO2 interface, with the reconstructed Pdc (100) facet more disordered than Pdi (111), verifying the existence of SMSI in such coupled system. The rearranged Pd atoms in the interface resulted in enhanced uricase-like catalytic activity, with Pdc@MnO2 demonstrating the best catalytic performance. Theoretical calculations suggested that a more disordered Pd interface led to stronger interactions with intermediates during the uricolytic process. In vitro cell experiments and in vivo therapy results demonstrated excellent biocompatibility, therapeutic effect, and biosafety for their potential hyperuricemia treatment. Our work provides a brand-new perspective for the design of highly efficient uricase-mimic catalysts.

Chitin nanocrystals-stabilized emulsion as template for fabricating injectable suspension containing polylactide hollow microspheres.

One of the promising applications of rod-like chitin nanocrystals (ChNCs) is the use as particle emulsifier to develop Pickering emulsions. We reported a ChNC-stabilized oil-in-water emulsion system, and developed a Pickering emulsion-templated method to prepare polylactide (PLA) hollow microspheres here. The results showed that both non-modified ChNCs and acetylated ChNCs could well emulsify the dichloromethane (DCM) solution of PLA-in-aqueous mannitol solution systems, forming very stable emulsions. At the same oil-to-water ratios and ChNC loadings, the emulsion stability was improved with increasing acetylation levels of ChNCs, accompanied by reduced size of droplets. Through the solvent evaporation, the PLA hollow microspheres were templated successfully, and the surface structure was also strongly dependent on the acetylation level of ChNCs. At a low level of acetylation, the single-hole or multi-hole surface structure formed, which was attributed to the out-diffusion of DCM caused by the solvent extraction and evaporation. These surface defects decreased with increased acetylation levels of ChNCs. Moreover, the aqueous suspension with as-obtained PLA microspheres revealed shear-thinning property and good biocompatibility, thereby had promising application as injectable fillers. This work can provide useful information around tuning surface structures of the Pickering emulsion-templated polymer hollow microspheres by regulating acetylation level of ChNCs.

Organo-Ptii Complexes for Potent Photodynamic Inactivation of Multi-Drug Resistant Bacteria and the Influence of Configuration.

PtII based organometallic photosensitizers (PSs) have emerged as novel potent photodynamic inactivation (PDI) reagents through their enhanced intersystem crossing (ISC) processes. Currently, few PtII PSs have been investigated as antibacterial materials, with relatively poor performances reported and with structure-activity relationships not well described. Herein, a pair of configurational isomers are reported of Bis-BODIPY (4,4-difluoro-boradizaindacene) embedded PtII PSs. The cis-isomer (cis-BBP) displayed enhanced 1O2 generation and better bacterial membrane anchoring capability as compared to the trans-isomer (trans-BBP). The effective PDI concentrations (efficiency > 99.9%) for cis-BBP in Acinetobacter baumannii (multi-drug resistant (MDR)) and Staphylococcus aureus are 400 nM (12 J cm-2) and 100 nM (18 J cm-2), respectively; corresponding concentrations and light doses for trans-BBP in the two bacteria are 2.50 µM (30 J cm-2) and 1.50 µM (18 J cm-2), respectively. The 50% and 90% minimum inhibitory concentration (MIC50 and MIC90) ratio of trans-BBP to cis-BBP is 22.22 and 24.02 in A. baumannii (MDR); 21.29 and 22.36 in methicillin resistant S. aureus (MRSA), respectively. Furthermore, cis-BBP displays superior in vivo antibacterial performance, with acceptable dark and photoinduced cytotoxicity. These results demonstrate cis-BBP is a robust light-assisted antibacterial reagent at sub-micromolecular concentrations. More importantly, configuration of PtII PSs should be an important issue to be considered in further PDI reagents design.

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.

Cerium-Luteolin Nanocomplexes in Managing Inflammation-Related Diseases by Antioxidant and Immunoregulation.

Oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and the antioxidant defense system, plays a pivotal role in inflammation-related diseases. Excessive ROS levels can induce cellular damage and impair normal physiological functions, triggering the release of inflammatory mediators and exacerbating the inflammatory response, ultimately leading to irreversible tissue damage. In this study, we synthesized cerium ion-luteolin nanocomplexes (CeLutNCs) by coordinating Ce ions with the natural product luteolin, aiming to develop a therapeutic agent with excellent antioxidant and immunoregulation properties for ROS-related inflammation treatment. In vitro experiments demonstrated that the prepared CeLutNCs effectively scavenged excess ROS, prevented cell apoptosis, down-regulated levels of important inflammatory cytokines, regulated the response of inflammatory macrophages, and suppressed the activation of the nuclear factor-κ-gene binding (NF-κB) pathway. In an acute kidney injury (AKI) animal model, CeLutNCs exhibited significant efficacy in improving kidney function, repairing damaged renal tissue, and reducing oxidative stress, inflammatory response, and cellular apoptosis. Moreover, the therapeutic potential of CeLutNCs in an acute lung injury (ALI) model was confirmed through the assessment of inflammatory responses and histopathological studies. This study emphasizes the effectiveness of these metal-natural product coordination nanocomplexes as a promising therapeutic approach for preventing AKI and other diseases associated with oxidative stress.

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.

Bacteria-targeted magnolol-loaded multifunctional nanocomplexes for antibacterial and anti-inflammatory treatment.

Natural plant-derived small molecules have shown great potential for their antimicrobial and anti-inflammatory properties. In this study, we successfully developed a nanocomplex consisting of magnolol (Mag), a surfactant with an 18 carbon hydrocarbon chain and multi-amine head groups (C18N3), and a peptide (cyclic 9-amino acid peptide (CARG)) with targeting capabilities forStaphylococcus aureus(S. aureus). The obtained Mag/C18N3/CARG nanocomplexes exhibited strong antibacterial activity againstS. aureus. Furthermore, they demonstrated anti-inflammatory effects by reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ßfrom macrophage inflammatory cells. This was achieved through downregulating the activation of NF-κB, KEAP1, and NRF2 signaling pathways. In a murine skin infection model, the Mag/C18N3/CARG nanocomplexes effectively suppressed the growth ofS. aureusin the infected area and promoted wound healing. Additionally, in a mouse model of acute kidney injury (AKI), the nanocomplexes significantly reduced the levels of blood urea nitrogen and creatinine, leading to a decrease in mortality rate. These findings demonstrate the potential of combining natural plant-derived small molecules with C18N3/CARG assemblies as a novel approach for the development of effective and safe antibacterial agents.

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.

In situ formation of ferrous sulfide in glycyrrhizic acid hydrogels to promote healing of multi-drug resistant Staphylococcus aureus-infected diabetic wounds.

Diabetic wound treatment faces great challenges in clinic. Staphylococcus aureus (S. aureus) is one of the most frequently isolated pathogens from the diabetic infections, which can severely impede wound healing time. Herein, ferrous sulfide (FeS) nanoparticles were fabricated through an in situ reaction between Fe2+ and S2- in glycyrrhizic acid (GA) solution. As the FeS nanoparticles aged, the solution gradually transformed into a gel, exhibiting excellent mechanical strength, injectability, and biocompatibility as a wound dressing. In addition to its own pharmacological effects, GA could act as the protector for FeS from oxidation of air. It also provided a weak acidic microenvironment, facilitating the pH-dependent dissolution reaction of FeS to release H2S and Fe2+. Notably, the effective antibacterial performance of the FeS/GA hydrogels towards S. aureus and multi-drug resistant S. aureus (MRSA) was achieved via the degradedly released Fe2+ and H2S through combination of ferroptosis damage and energy metabolism disruption. Moreover, FeS/GA hydrogels effectively modulated the proportion of M1/M2 macrophages, reduced the secretion of inflammatory cytokines, and significantly enhanced the proliferation and migration of fibroblasts in vitro. Importantly, in an MRSA-infected diabetic wound model, the FeS/GA hydrogels efficiently eradicated bacteria and regulated the inflammatory microenvironment, thereby promoting the diabetic wound repair. Overall, our study establishes a novel strategy for developing multifunctional hydrogels that serve as an effective therapeutic platform for managing bacteria-infected diabetic wounds.

Synthesis of Ti3C2T x /MnO2 composites for synergistic catalytic/photothermal-based bacterial inhibition.

Human inflammation caused by bacterial infection threatens global public health. The abuse of antibiotics often leads to the development of drug resistance in bacteria. To address this issue, nanozymes with peroxidase-like (POD-like) activity have often been reported for bacteriostasis with the assistance of catalytic substrate hydrogen peroxide (H2O2). However, it is difficult to achieve efficient bactericidal outcomes only through exertion of the POD-like activity of nanozymes. Here, MnO2 loaded Ti3C2T x (Ti3C2T x /MnO2) was prepared by a two-step reaction method, in which MnO2 showed high oxidase-like (OXD-like) activity to elevate the levels of reactive oxygen species (ROS) without H2O2 and Ti3C2T x exhibited high photothermal conversion efficiency to induce hyperthermia. Thus, the obtained Ti3C2T x /MnO2 realized synergistic catalytic/photothermal-based bacterial inhibition, including for Gram-negative bacteria (Escherichia coli), Gram-positive bacteria (Staphylococcus aureus), and methicillin-resistant Staphylococcus aureus. Importantly, Ti3C2T x /MnO2 with near-infrared light irradiation successfully promoted Staphylococcus aureus-infected wound healing in mouse models, representing an alternative treatment to fight against bacterial infection.

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.

Fluorescent Nitrogen-Doped Carbon Dots for Label Live Elder Blood-Stage Plasmodium falciparum through New Permeability Pathways.

To verify the size and emergence time of new permeability pathways (NPPs) in malaria parasites, the permeability of the Plasmodium falciparum-infected erythrocytes was tested with different particle sizes of nanomaterials by flow cytometry assay. The results confirmed the permeability of the host cell membrane increases with parasite maturation for the stage-development evolution of NPPs, and especially found that a particle size of about 50 nm had higher efficiency. As a kind of the novel nanomaterials, nitrogen-doped carbon dots (NCDs) showed no toxicity, specificity binding ability to the malaria parasites, and could label live elder blood-stage P. falciparum through NPPs, indicating the potential application in cell imaging. NPPs and some nanomaterials such as NCDs deserve more attention and exploration for the elimination and prevention of malaria.

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.