An Engineered Nanoplatform with Tropism toward Irradiated Glioblastoma Augments Its Radioimmunotherapy Efficacy.

Combining radiotherapy with immune checkpoint blockade therapy offers a promising approach to treat glioblastoma multiforme (GBM), yet challenges such as limited effectiveness and immune-related adverse events (irAEs) persist. These issues are largely due to the failure in targeting immunomodulators directly to the tumor microenvironment. To address this, we developed a biomimetic nanoplatform that combines a genetically modified mesenchymal stem cell (MSC) membrane with a bioactive nanoparticle core for chemokine-directed radioimmunotherapy of GBM. The CCR2-overexpressing MSC membrane acts as a tactical tentacle to achieve radiation-induced tropism toward the abundant chemokine ligand CCL2 in irradiated gliomas. The nanoparticle core, comprising diselenide-bridged mesoporous silica nanoparticles (MSNs) and PD-L1 antibodies (αPD-L1), enables X-ray-responsive drug release and radiosensitization. In two murine models with orthotopic GBM tumors, this nanoplatform reinvigorated immunogenic cell death, and augmented the efficacy and specificity of GBM radioimmunotherapy, with reduced occurrence of irAEs. This study suggests a promising radiation-induced tropism strategy for targeted drug delivery, and presents a potent nanoplatform that enhances the efficacy and safety of radio-immunotherapy. This article is protected by copyright. All rights reserved.

Hepatic-Accumulated Obeticholic Acid and Atorvastatin Self-Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic-Associated Fatty Liver Disease.

Exploration of medicines for efficient and safe management of metabolic-associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic-targeted nanodrugs composed of OCA and cholesterol-lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier-free nanocrystals (OCAHTs) are self-assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter-mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen-challenged mice and high-fat diet-induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD-associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter-based strategy for hepatic-targeting drug delivery but also presents an efficient and safe full-API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD.

Bioactive mesoporous silica nanoparticle-functionalized titanium implants with controllable antimicrobial peptide release potentiate the regulation of inflammation and osseointegration.

Bacterial infection and delayed osseointegration are two major challenges for titanium-based orthopedic implants. In the present study, we developed a functionalized titanium implant Ti-M@A by immobilizing antimicrobial peptide (AMP) HHC36-loaded diselenide-bridged mesoporous silica nanoparticles (MSNs) on the surface, which showed good long-term and mechanical stability. The functionalized implants can realize the sustained release of AMP over 30 days and exhibit over 95.71 % antimicrobial activity against four types of clinical bacteria (S. aureus, E. coli, P. aeruginosa and MRSA), which arose from the capability to destroy the bacterial membranes. Moreover, Ti-M@A can efficiently inhibit the biofilm formation of the bacteria. The functionalized implants can also significantly promote the osteogenic differentiation of mouse bone marrow-derived mesenchymal stem cells (mBMSCs) because of the Se in MSNs. Notably, it can trigger macrophages toward M2 polarization in vitro by scavenging ROS in LPS-activated macrophages. Consequently, in vivo assays with infection and non-infection bone defect models demonstrated that such bioactive implants can not only kill over 98.82 % of S. aureus, but also promote osseointegration. Hence, this study provides a combined strategy to resolve bacterial infection and delayed osseointegration for titanium implants.

Leveraging Radiation-triggered Metal Prodrug Activation Through Nanosurface Energy Transfer for Directed Radio-chemo-immunotherapy.

Metal-based drugs currently dominate the field of chemotherapeutic agents; however, achieving the controlled activation of metal prodrugs remains a substantial challenge. Here, we propose a universal strategy for the radiation-triggered activation of metal prodrugs via nanosurface energy transfer (NSET). The core-shell nanoplatform (Ru-GNC) is composed of gold nanoclusters (GNC) and ruthenium (Ru)-containing organic-inorganic hybrid coatings. Upon X-ray irradiation, chemotherapeutic Ru (II) complexes were released in a controlled manner through a unique NSET process involving the transfer of photoelectron energy from the radiation-excited Ru-GNCs to the Ru-containing hybrid layer. In contrast to the traditional radiation-triggered activation of prodrugs, such an NSET-based system ensures that the reactive species in the tumor microenvironment are present in sufficient quantity and are not easily quenched. Additionally, ultrasmall Ru-GNCs preferably target mitochondria and profoundly disrupt the respiratory chain upon irradiation, leading to radiosensitization by generating abundant reactive oxygen species. Consequently, Ru-GNC-directed radiochemotherapy induces immunogenic cell death, resulting in significant therapeutic outcomes when combined with the programmed cell death-ligand 1 (PD-L1) checkpoint blockade. This NSET strategy represents a breakthrough in designing radiation-triggered nanoplatforms for metal-prodrug-mediated cancer treatment in an efficient and controllable manner.

Engineering a biomimetic system for hepatocyte-specific RNAi treatment of non-alcoholic fatty liver disease.

RNA interference (RNAi) presents great potential against intractable liver diseases. However, the establishment of specific, efficient, and safe delivery systems targeting hepatocytes remains a great challenge. Herein, we described a promising hepatocytes-targeting system through integrating triantennary N-acetylgalactosamine (GalNAc)-engineered cell membrane with biodegradable mesoporous silica nanoparticles, which efficiently and safely delivered siRNA to hepatocytes and silenced the target PCSK9 gene expression for the treatment of non-alcoholic fatty liver disease. Having optimized the GalNAc-engineering strategy, insertion orders, and cell membrane source, we obtained the best-performing GalNAc-formulations allowing strong hepatocyte-specific internalization with reduced Kupffer cell capture, resulting in robust gene silencing and less hepatotoxicity when compared with cationic lipid-based GalNAc-formulations. Consequently, a durable reduction of lipid accumulation and damage was achieved by systemic administering siRNAs targeting PCSK9 in high-fat diet-fed mice, accompanied by displaying desirable safety profiles. Taken together, this GalNAc-engineering biomimetics represented versatile, efficient, and safe carriers for the development of hepatocyte-specific gene therapeutics, and prevention of metabolic diseases. STATEMENT OF SIGNIFICANCE: Compared to MSN@LP-GN3 (MC3-LNP), MSN@CM-GN3 exhibited strong hepatocyte targeting and Kupffer cell escaping, as well as good biocompatibility for safe and efficient siRNA delivery. Furthermore, siPCSK9 delivered by MSN@CM-GN3 reduced both serum and liver LDL-C, TG, TC levels and lipid droplets in HFD-induced mice, resulting in better performance than MSN/siPCSK9@LP-GN3 in terms of lipid-lowering effect and safety profiles. These findings indicated promising advantages of our biomimetic GN3-based systems for hepatocyte-specific gene delivery in chronic liver diseases. Our work addressed the challenges associated with the lower targeting efficiency of cell membrane-mimetic drug delivery systems and the immunogenicity of traditional GalNAc delivery systems. In conclusion, this study provided an effective and versatile approach for efficient and safe gene editing using ligand-integrated biomimetic nanoplatforms.

Association between periodontitis and mortality of patients with cardiovascular diseases: A cohort study based on NHANES.

BACKGROUND: The association between periodontitis and cardiovascular disease (CVD) has been widely explored, but little is known about the effect of periodontitis on the mortality of CVD patients. This study aims to clarify the effect of periodontitis on all-cause and cause-specific mortality of CVD patients. METHODS: We included 2,135 individuals with CVD from the National Health and Nutrition Examination Survey. Mortality data were ascertained by linkage to National Death Index records through 31 December 2019. We used Cox proportional hazards models for all-cause mortality and competing risk models for CVD and cancer mortality to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Further covariate adjustments, stratification analyses, and a variety of sensitivity analyses were conducted to test the reliability and robustness of the results. RESULTS: The all-cause mortality in CVD patients with moderate/severe periodontitis was significantly higher than in those with no/mild periodontitis (HR: 1.25; 95% CI: 1.02-1.52; P = 0.03). The all-cause mortality in participants with severe clinical attachment loss was significantly higher (HR: 1.07; 95% CI: 1.01-1.14; P = 0.01). However, no discrepancy in CVD or cancer mortality was observed between CVD patients with different periodontal status. CONCLUSIONS: Our findings from a longitudinal study with a large sample indicated significant but slightly higher all-cause mortality in CVD patients with moderate/severe periodontitis than in those with no/mild periodontitis.

Intravenous Senescent Erythrocyte Vaccination Modulates Adaptive Immunity and Splenic Complement Production.

Targeted delivery of vaccines to the spleen remains a challenge. Inspired by the erythrophagocytotic process in the spleen, we herein report that intravenous administration of senescent erythrocyte-based vaccines profoundly alters their tropism toward splenic antigen-presenting cells (APCs) for imprinting adaptive immune responses. Compared with subcutaneous inoculation, intravenous vaccination significantly upregulated splenic complement expression in vivo and demonstrated synergistic antibody killing in vitro. Consequently, intravenous senescent erythrocyte vaccination produces potent SARS-CoV-2 antibody-neutralizing effects, with potential protective immune responses. Moreover, the proposed senescent erythrocyte can deliver antigens from resected tumors and adjuvants to splenic APCs, thereby inducing a personalized immune reaction against tumor recurrence after surgery. Hence, our findings suggest that senescent erythrocyte-based vaccines can specifically target splenic APCs and evoke adaptive immunity and complement production, broadening the tools for modulating immunity, helping to understand adaptive response mechanisms to senescent erythrocytes better, and developing improved vaccines against cancer and infectious diseases.

Novel STAT1 mutation in a paediatric case of chronic mucocutaneous candidiasis complicated by primary hypothyroidism: clinical presentation, genetic analysis and prognostic implications.

This case report presents a young girl in her early childhood diagnosed with chronic mucocutaneous candidiasis (CMC) and primary hypothyroidism. Genetic analysis revealed a novel de novo mutation in the STAT1 gene (exon 11, c.972C>G, p.Cys324Trp), adding to the existing literature on STAT1 mutations, which account for approximately 53% of CMC cases. The identified mutation is predicted to have a more severe pathogenic impact based on PolyPhen-2 scoring. Our findings emphasise the importance of comprehensive genetic testing in CMC diagnosis and suggest that the specific mutation site may correlate with disease prognosis. The case underscores the need for vigilant monitoring and targeted therapeutic interventions, given the potential for poorer outcomes.

Cationic mesoporous silica nanoparticles alleviate osteoarthritis by targeting multiple inflammatory mediators.

Osteoarthritis (OA) is a common and complex inflammatory disorder that is frequently compounded by cartilage degradation, synovial inflammation, and osteophyte formation. Damaged chondrocytes release multiple danger mediators that exacerbate synovial inflammation and accelerate the progression to OA. Conventional treatments targeting only a single mediator of OA have failed to achieve a strong therapeutic effect. Addressing the crucial role of multiple danger mediators in OA progression, we prepared polyethylenimine (PEI)-functionalized diselenide-bridged mesoporous silica nanoparticles (MSN-PEI) with cell-free DNA (cfDNA)-binding and anti-oxidative properties. In models of surgery-induced and collagenase-induced arthritis, we showed that these cationic nanoparticles attenuated cartilage degradation and provided strong chondroprotection against joint damage. Mechanistically, multiple target blockades alleviated oxidative stress and dampened cfDNA-induced inflammation by suppressing the M1 polarization of macrophages. This study suggests a beneficial direction for targeting multiple danger mediators in the treatment of intractable arthritis.

X-ray-controllable release of carbon monoxide potentiates radiotherapy by ultrastable hybrid nanoreservoirs.

Carbon monoxide (CO) exhibits unique abilities in sensitizing cancer radiotherapy (RT). However, the development of a highly stable CO-delivery nanosystem with sustained CO release in tumor tissues and the prevention of CO leakage into normal tissues remains a challenge. Herein, an organic-inorganic hybrid strategy is proposed to create ultrastable CO nanoreservoirs by locking an unstable iron carbonyl (FeCO) prodrug in a stable mesoporous silica matrix. Different from traditional FeCO-loading nanoplatforms, FeCO-bridged nanoreservoirs not only tethered labile FeCO in the framework to prevent unwanted FeCO leakage, but also achieved sustained CO release in response to X-ray and endogenous H2O2. Importantly, FeCO-bridged nanoreservoirs exhibited the sequential release of CO and Fe2+, thereby performing highly efficient chemodynamic therapy. Such a powerful combination of RT, gas therapy, and chemodynamic therapy boosts robust immunogenic cell death, thus enabling the elimination of deeply metastatic colon tumors with minimal side effects. The proposed organic-inorganic hybrid strategy opens a new window for the development of stable nanoreservoirs for the on-demand delivery of unstable gases and provides a feasible approach for the sequential release of CO and metal ions from metal carbonyl complexes.

Thiol-Disulfide Exchange Coordinates the Release of Nitric Oxide and Dexamethasone for Synergistic Regulation of Intestinal Microenvironment in Colitis.

The cell-specific functions of nitric oxide (NO) in the intestinal microenvironment orchestrate its therapeutic effects in ulcerative colitis. While most biomaterials show promise by eliciting the characteristics of NO, the insufficient storage, burst release, and pro-inflammatory side effects of NO remain as challenges. Herein, we report the development of thiol-disulfide hybrid mesoporous organosilica nanoparticles (MONs) that improve the storage and sustained release of NO, broadening the therapeutic window of NO-based therapy against colitis. The tailored NO-storing nanomaterials coordinated the release of NO and the immunoregulator dexamethasone (Dex) in the intestinal microenvironment, specifically integrating the alleviation of oxidative stress in enterocytes and the reversal of NO-exacerbated macrophage activation. Mechanistically, such a synchronous operation was achieved by a self-motivated process wherein the thiyl radicals produced by NO release cleaved the disulfide bonds to degrade the matrix and release Dex via thiol-disulfide exchange. Specifically, the MON-mediated combination of NO and Dex greatly ameliorated intractable colitis compared with 5-aminosalicylic acid, even after delayed treatment. Together, our results reveal a key contribution of synergistic modulation of the intestinal microenvironment in NO-based colitis therapy and introduce thiol-disulfide hybrid nanotherapeutics for the management of inflammatory diseases and cancer.

Tumor-targeted bioactive nanoprobes visualizing of hydrogen peroxide for forecasting chemotherapy-exacerbated malignant prognosis.

Introduction: Fluorescent visualization of hydrogen peroxide in the tumor microenvironment (TME) is conducive to predicting malignant prognosis after chemotherapy. Two photon microscopy has been employed for in vivo hydrogen peroxide detection owing to its advantages of deep penetration and low phototoxicity. Methods: In this study, a two-photon fluorescent probe (TPFP) was protected by mesoporous silica nanoparticles (MSNs) and masked by cloaking the cancer cell membranes (CM), forming a tumor-targeted bioactive nanoprobe, termed MSN@TPFP@CM. Results: This multifunctional nanoprobe allowed for the effective and selective detection of excessive hydrogen peroxide production in chemotherapeutic Etoposide (VP-16)-challenged tumor cells using two-photon microscopy. After specific accumulation in tumors, VP-16-MSN@TPFP@CM monitored tumor-specific hydrogen peroxide levels and revealed a positive correlation between oxidative stress in the TME and chemotherapy-exacerbated malignant prognosis. Discussion: Given the recent translation of fluorescent imaging into early clinical trials and the high biocompatibility of bioactive nanoprobes, our approach may pave the way for specific imaging of oxidative stress in solid tumors after treatment and provide a promising technology for malignant prognosis predictions.

Self-polymerized platinum (II)-Polydopamine nanomedicines for photo-chemotherapy of bladder Cancer favoring antitumor immune responses.

Systemic administration of platinum-based drugs has obvious limitations in the treatment of advanced bladder cancer (BC) owing to lower tumor accumulation and uncontrolled release of chemotherapeutics. There is an urgent need for advanced strategies to overcome the current limitations of platinum-based chemotherapy, to achieve maximal therapeutic outcomes with reduced side effects. In this study, self-polymerized platinum (II)-polydopamine nanocomplexes (PtPDs) were tailored for efficient chemo-photoimmunotherapy of BC. PtPDs with high Pt loading content (11.3%) were degradable under the combination of a reductive tumor microenvironment and near-infrared (NIR) light irradiation, thus controlling the release of Pt ions to achieve efficient chemotherapy. In addition, polydopamine promoted stronger photothermal effects to supplement platinum-based chemotherapy. Consequently, PtPDs provided effective chemo-photothermal therapy of MB49 BC in vitro and in vivo, strengthening the immunogenic cell death (ICD) effect and robust anti-tumoral immunity response. When combined with a PD-1 checkpoint blockade, PtPD-based photochemotherapy evoked systemic immune responses that completely suppressed primary and distant tumor growth without inducing systemic toxicities. Our work provides a highly versatile approach through metal-dopamine self-polymerization for the precise delivery of metal-based chemotherapeutic drugs, and may serve as a promising nanomedicine for efficient and safe platinum-based chemotherapy for BC.

Nanoparticle-Mediated CD47-SIRPα Blockade and Calreticulin Exposure for Improved Cancer Chemo-Immunotherapy.

Enabling macrophages to phagocytose tumor cells holds great potential for cancer therapy but suffers from tremendous challenges because the tumor cells upregulate antiphagocytosis molecules (such as CD47) on their surface. The blockade of CD47 alone is insufficient to stimulate tumor cell phagocytosis in solid tumors due to the lack of "eat me" signals. Herein, a degradable mesoporous silica nanoparticle (MSN) is reported to simultaneously deliver anti-CD47 antibodies (aCD47) and doxorubicin (DOX) for cancer chemo-immunotherapy. The codelivery nanocarrier aCD47-DMSN was constructed by accommodating DOX within the mesoporous cavity, while adsorbing aCD47 on the surface of MSN. aCD47 blocks the CD47-SIRPα axis to disable the "don't eat me" signal, while DOX induces immunogenic tumor cell death (ICD) for calreticulin exposure as an "eat me" signal. This design facilitated the phagocytosis of tumor cells by macrophages, which enhanced antigen cross-presentation and elicited efficient T cell-mediated immune response. In 4T1 and B16F10 murine tumor models, aCD47-DMSN generated a strong antitumor effect after intravenous injection by increasing tumor-infiltration of CD8+ T cells. Taken together, this study offers a nanoplatform to modulate the phagocytosis of macrophages for efficacious cancer chemo-immunotherapy.

Nanomaterials against intracellular bacterial infection: from drug delivery to intrinsic biofunction.

Fighting intracellular bacteria with strong antibiotics evading remains a long-standing challenge. Responding to and regulating the infectious microenvironment is crucial for treating intracellular infections. Sophisticated nanomaterials with unique physicochemical properties exhibit great potential for precise drug delivery towards infection sites, along with modulating infectious microenvironment via their instinct bioactivity. In this review, we first identify the key characters and therapeutic targets of intracellular infection microenvironment. Next, we illustrate how the nanomaterials physicochemical properties, such as size, charge, shape and functionalization affect the interaction between nanomaterials, cells and bacteria. We also introduce the recent progress of nanomaterial-based targeted delivery and controlled release of antibiotics in intracellular infection microenvironment. Notably, we highlight the nanomaterials with unique intrinsic properties, such as metal toxicity and enzyme-like activity for the treatment of intracellular bacteria. Finally, we discuss the opportunities and challenges of bioactive nanomaterials in addressing intracellular infections.

Leveraging ß-Adrenergic Receptor Signaling Blockade for Improved Cancer Immunotherapy Through Biomimetic Nanovaccine.

The establishment of effective antitumor immune responses of vaccines is mainly limited by insufficient priming tumor infiltration of T cells and immunosuppressive tumor microenvironment (TME). Targeting ß-adrenergic receptor (ß-AR) signaling exerts promising benefits on reversing the suppressive effects directly on T cells, but it appears to have considerably limited antitumor performance when combined with vaccine-based immunotherapies. Herein, a tumor membrane-coated nanoplatform for codelivery of adjuvant CpG and propranolol (Pro), a ß-AR inhibitor is designed. The biomimetic nanovaccine displayed an improved accumulation in lymph nodes and sufficient drug release, thereby inducing dendritic cell maturation and antigen presentation. Meanwhile, the integration of vaccination and blockade of ß-AR signaling not only promoted the priming of the naive CD8+ T cells and effector T cell egress from lymph nodes, but also alleviated the immunosuppressive TME by decreasing the frequency of immunosuppressive cells and increasing the tumor infiltration of B cells and NK cells. Consequently, the biomimetic nanovaccines outperformed greater prophylactic and therapeutic efficacy than nanovaccines without Pro encapsulation in B16-F10 melanoma mice. Taken together, the work explored a biomimetic nanovaccine for priming tumor infiltration of T cells and immunosuppressive TME regulation, offering tremendous potential for a combined ß-AR signaling-targeting strategy in cancer immunotherapy.

Biomimetic Nanovaccines Potentiating Dendritic Cell Internalization via CXCR4-Mediated Macropinocytosis.

Although targeted delivery of nanoparticulate vaccines to dendritic cells (DCs) holds tremendous potential, it still faces insufficient internalization and endosome degradation via the receptor-mediated endocytosis pathway. Inspired by the advantages of CXC-chemokine receptor type 4 (CXCR4)-mediated macropinocytosis in the internalization of DCs, a multifunctional vaccine is constructed based on a reactive oxygen species (ROS)-responsive nanoparticulate core and macropinocytosis-inducing peptide-fused cancer membrane shell, allowing the direct cytosolic delivery of cancer membrane-associated antigen and a stimulator of interferon genes (STING) agonist, cGAMP for highly efficient cancer immunotherapy. The biomimetic nanovaccines show a dramatically enhanced cellular uptake by DCs via CXCR4-mediated macropinocytosis. Such a direct delivery process promotes cytosolic release of cGAMP in response to ROS, and together promoted DC maturation and T cell priming by activating the STING pathway. Consequently, the biomimetic nanovaccines not only result in a great tumor rejection in prophylactic B16-F10 melanoma murine model, but also markedly suppress the growth of established melanoma tumors when combined with anti-PD-1 checkpoint blockade. This study advances the design of biomimetic nanovaccines and provides a promising strategy for macropinocytosis-mediated cancer vaccination.

Probiotic-Inspired Nanomedicine Restores Intestinal Homeostasis in Colitis by Regulating Redox Balance, Immune Responses, and the Gut Microbiome.

Microbiota-based therapeutics offer innovative strategies to treat inflammatory bowel diseases (IBDs). However, the poor clinical outcome so far and the limited flexibility of the bacterial approach call for improvement. Inspired by the health benefits of probiotics in alleviating symptoms of bowel diseases, bioartificial probiotics are designed to restore the intestinal microenvironment in colitis by regulating redox balance, immune responses, and the gut microbiome. The bioartificial probiotic comprises two components: an E. coli Nissle 1917-derived membrane (EM) as the surface and the biodegradable diselenide-bridged mesoporous silica nanoparticles (SeM) as the core. When orally administered, the probiotic-inspired nanomedicine (SeM@EM) adheres strongly to the mucus layer and restored intestinal redox balance and immune regulation homeostasis in a murine model of acute colitis induced by dextran sodium sulfate. In addition, the respective properties of the EM and SeM synergistically alter the gut microbiome to a favorable state by increasing the bacterial diversity and shifting the microbiome profile to an anti-inflammatory phenotype. This work suggests a safe and effective nanomedicine that can restore intestinal homeostasis for IBDs therapy.

A multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT) eradicates tumors by intratumoral catalytic chemical reaction and subsequently disrupts redox homeostasis, which shows tumor specific reactive oxygen species (ROS)-mediated therapy. However, insufficient ROS generation and high levels of glutathione (GSH) in cancer cells have limited the therapeutic efficacy of CDT. Herein, we constructed a multifunctional oxidative stress nanoamplifier with ROS amplification and GSH exhaustion for enhanced CDT. Such a sandwich-like nanoamplifier comprised layer-by-layer artesunate (AS) and calcium carbonate coatings on the surface of manganese dioxide (MnO2) nanoparticles. The nanoamplifier was disassembled under an acidic environment once accumulated into tumor sites, and subsequently released AS to replenish the intratumoral peroxide pool for ROS amplification. Besides being an AS carrier, MnO2 exhausted GSH to yield Mn2+ ions that catalyzed the overexpression of H2O2 in the tumor, further intensifying the oxidative stress and facilitating cancer cell death. Taken together, our findings not only provide a paradigm for fabricating intratumoral catalytic nanomaterials, but also present a new ROS enhancement strategy to improve anti-tumor efficacy. Our multifunctional oxidative stress nanoamplifier might broaden the future of CDT.

Self-Assembled Ru(II)-Coumarin Complexes for Selective Cell Membrane Imaging.

The cell membrane, as the protecting frontier of cells, is closely related to crucial biological behaviors including cell growth, death, and division. Lots of fluorescent probes have been fabricated to monitor cell membranes due to their simplicity and intuitiveness. However, the efficiency of those traditional probes has been limited by their susceptibility to photobleaching and poor water solubility. In this study, we have reported Ru(II)-coumarin complexes consisting of ruthenium, 1,10-phenanthroline, and coumarin 6 to further form self-assembled nanoprobes, for cell membrane targeting and imaging. The fluorescent property could be switchable from red to green through the dynamic disassembly of nanoprobes. Compared with commercial Dil, biocompatible nanoprobes exhibited superior stability for long-term cell imaging, along with remarkedly reduced background interference. Therefore, our self-assembled nanoprobe provides a powerful solution for investigating lipid trafficking with optical imaging.