Construction of a point-of-care electrochemical biosensor for Escherichia coli 16S rRNA analysis based on MoS2 nanoprobes.

Foodborne pathogens are harmful to human health because they can contaminate food and induce diseases. To efficiently distinguish and determine foodborne bacteria, an ultrasensitive point-of-care electrochemical biosensor was designed for 16S rRNA detection by coupling a signal amplification strategy with MoS2-based nanoprobes. Gold nanoparticles and thionine co-functionalized molybdenum disulfide (MoS2) nanocomposites (MoS2-Thi-AuNPs) were used to construct nanoprobes, which can efficiently monitor the detection process and amplify the detection signal. In the presence of Escherichia coli (E. coli) 16S rRNA, a classical sandwiched DNA structure was formed on the surface of a hierarchical flower-like gold nanostructure-decorated screen-printed carbon electrode (HFGN-SPCE), generating an obvious electrochemical signal from Thi. Under optimal conditions, this designed electrochemical biosensor showed a wide dynamic range (0-1.0 × 106 fM), low detection limit (2.8 fM), high selectivity and accepted stability for E. coli 16S rRNA detection in ideal buffers. Moreover, this biosensor can efficiently determine 16S rRNA in milk samples and 10 CFU mL-1 bacterial lysate. All experimental results suggested that this biosensor has a promising application in the detection of foodborne pathogens.

Elastic Nanovaccine Enhances Dendritic Cell-Mediated Tumor Immunotherapy.

Nanovaccine-based immunotherapy (NBI) has the ability to initiate dendritic cell (DC)-mediated tumor-specific immune responses and maintain long-term antitumor immune memory. To date, the mechanism by which the mechanical properties of nanoparticles alter the functions of DCs in NBI remains largely unclear. Here, a soft mesoporous organosilica-based nanovaccine (SMONV) is prepared and the elasticity-dependent effect of the nanovaccine on the underlying DC-mediated immune responses is studied. It is found that the elasticity results in greater internalization of SMONV by DCs, followed by the induction of substantial cytosolic delivery of antigens via endosomal escape, leading to effective DC maturation and antigen cross-presentation. Impressively, elasticity enables SMONV to enhance lymphatic drainage of antigens in vivo, thus stimulating robust humoral and cellular immunity. The results from therapeutic tumor vaccination further reveal that subcutaneously administered SMONV effectively suppresses tumor growth in tumor-bearing mice by evoking antigen-specific CD8+ T-cell immune responses, mitigating regulatory T-cell-mediated immunosuppression, and increasing central memory and effector memory T-cell populations. Furthermore, combinatorial immunization with SMONV and anti-PD-L1 blocking antibodies results in an amplified therapeutic effect on tumor-bearing mice. These findings reveal the elastic effect of the nanovaccine on DC-mediated immune responses, and the prepared SMONV represents a facile and powerful strategy for antitumor immunotherapy.

Dysbiosis of gut microbiota and intestinal damage in mice induced by a single intravenous exposure to CdTe quantum dots at low concentration.

Although quantum dots (QDs) have shown great potential for various biomedical applications, their potential toxicity still needs to be comprehensively investigated. Previous studies showed that intravenous exposure of CdTe QDs at low concentration did not lead to obvious in vivo toxicity in the long term. However, the influence of CdTe QDs on the gut microbiota and the intestine is still unknown. Here, we explored whether single intravenous injection of CdTe QDs at low concentration can affect the gut microbiota and intestine of mice in short term. The results showed that CdTe QDs caused an imbalance of gut microbiota, especially the rapid increase in Lactobacillus on day 1 post-treatment. Meanwhile, the intestine exhibited the promotion of oxidative stress, inflammatory response, and hemorrhaging on days 5 and 15. These results demonstrate that the gut microbiota and the intestine are very sensitive to the toxicity of low-concentration CdTe QDs. This study provides further insight and method for the biosafety evaluation of nanomaterials.

Efficient Preparation of Small-Sized Transition Metal Dichalcogenide Nanosheets by Polymer-Assisted Ball Milling.

Two-dimensional (2D) transition metal dichalcogenide nanosheets (TMDC NSs) have attracted growing interest due to their unique structure and properties. Although various methods have been developed to prepare TMDC NSs, there is still a great need for a novel strategy combining simplicity, generality, and high efficiency. In this study, we developed a novel polymer-assisted ball milling method for the efficient preparation of TMDC NSs with small sizes. The use of polymers can enhance the interaction of milling balls and TMDC materials, facilitate the exfoliation process, and prevent the exfoliated nanosheets from aggregating. The WSe2 NSs prepared by carboxymethyl cellulose sodium (CMC)-assisted ball milling have small lateral sizes (8~40 nm) with a high yield (~60%). The influence of the experimental conditions (polymer, milling time, and rotation speed) on the size and yield of the nanosheets was studied. Moreover, the present approach is also effective in producing other TMDC NSs, such as MoS2, WS2, and MoSe2. This study demonstrates that polymer-assisted ball milling is a simple, general, and effective method for the preparation of small-sized TMDC NSs.

Cu2 MoS4 Nanozyme with NIR-II Light Enhanced Catalytic Activity for Efficient Eradication of Multidrug-Resistant Bacteria.

Nanozymes with unique enzyme-like catalytic properties and versatile functionalities are particularly attractive for the treatment of bacterial infections, especially for combating drug-resistant bacteria. However, inherently low catalytic activity significantly limits their antibacterial performance. Herein, a new near-infrared II (NIR-II) light responsive nanozyme (Cu2 MoS4 nanoplates, CMS NPs) is developed for efficient eradication of multidrug-resistant (MDR) bacteria. CMS NPs with intrinsic dual enzyme-like property can generate reactive oxygen species (ROS) by catalysis. Importantly, CMS NPs show NIR-II light enhanced oxidase- and peroxidase-like catalytic activities to improve ROS generation for highly efficient killing of bacteria. In vitro results demonstrate that CMS NPs (40 µg mL-1 ) achieve rapid killing of 8 log MDR Escherichia coli and 6 log MDR Staphylococcus aureus (S. aureus) under NIR-II light irradiation (1064 nm, 1 W cm-2 ) in 10 min. Moreover, CMS NPs exhibit excellent therapeutic efficacy of MDR S. aureus infection in vivo as well as negligible toxicity to cells and animals, indicating their potential use as antibacterial agents. This work provides a novel antibacterial strategy by combining the catalytic generation of ROS and NIR-II photothermal effect of nanozymes for efficient treatment of MDR bacteria-related infections.

Gut microbiota and lipid metabolism alterations in mice induced by oral cadmium telluride quantum dots.

The potential toxicity of cadmium-containing quantum dots (QDs) has received much attention because of increasing biomedical applications. However, little has been known about how cadmium telluride (CdTe) QDs influence the gut microbiota and lipid metabolism. In this study, mice were exposed orally to CdTe QDs (200 µL of 0.2, 2, 20 or 200 µm; twice per week) for 4 weeks. The oral experiments showed CdTe QD exposure led to a decrease of the Firmicutes/Bacteroidetes (F/B) ratio of gut microbiota, which highly negatively correlated with the low-density lipoprotein (LDL), triglyceride (TG) and total cholesterol (TC) levels in serum. In addition, the low-dose (0.2 and 2 µm) CdTe QDs significantly increased the diversity of gut microbiota, and did not elevate the LDL, TG and TC levels in serum. The medium dose (20 µm) of CdTe QDs caused the biggest decrease of the F/B ratio, so it significantly increased the LDL, TG and TC levels compared with the control. Furthermore, high-dose (200 µm) CdTe QDs caused various toxicities in the histopathology of liver and intestine, liver function and intestinal immunity, but did not significantly lead to changes of the LDL, TG and TC levels in serum. This study demonstrates that high-dose oral CdTe QDs mainly lead to tissue damage of the liver and intestine, while the medium and low doses of oral CdTe QDs induce shifts of gut microbiota structure, which are associated with blood lipid levels.

Reduction of graphene oxide quantum dots to enhance the yield of reactive oxygen species for photodynamic therapy.

The production of reactive oxygen species (ROS) from graphene oxide quantum dots (GOQDs) and chemically reduced GOQDs (rGOQDs) was studied. This shows that GOQDs and rGOQDs produce ROS including singlet oxygen (1O2), hydrogen peroxide (H2O2) and superoxide anion (O2˙-). Interestingly, the rGOQDs exhibit a higher yield of ROS under white light in comparison with GOQDs, indicating the enhanced photodynamic effect through chemical reduction of GOQDs. Studies on the relation between their structures and the yield of ROS demonstrate that the reduction of GOQDs with hydrazine hydrate decreases the band gap and valence band of GOQDs and results in more electron-hole pairs, which leads to an improvement in the yield of ROS from rGOQDs. This research explores the specific species of ROS generated from GOQDs, and provides an efficient avenue to improve the yield of ROS through surface modification of GOQDs.

Recent Advances in Synthesis and Biomedical Applications of Two-Dimensional Transition Metal Dichalcogenide Nanosheets.

During recent decades, a giant leap in the development of nanotechnology has been witnessed. Numerous nanomaterials with different dimensions and unprecedented features have been developed and provided unimaginably wide scope to solve the challenging problems in biomedicine, such as cancer diagnosis and therapy. Recently, two-dimensional (2D) transition metal dichalcogenide (TMDC) nanosheets (NSs), including MoS2 , WS2 , and etc., have emerged as novel inorganic graphene analogues and attracted tremendous attention due to their unique structures and distinctive properties, and opened up great opportunities for biomedical applications, including ultrasensitive biosensing, biological imaging, drug delivery, cancer therapy, and antibacterial treatment. A comprehensive overview of different synthetic methods of ultrathin 2D TMDC NSs and their state-of-the-art biomedical applications, especially those that have appeared in the past few years, is presented. At the end of this review, the future opportunities and challenges for 2D TMDC NSs in biomedicine are also discussed.

Facile Synthesis of Yolk-Shell-Structured Triple-Hybridized Periodic Mesoporous Organosilica Nanoparticles for Biomedicine.

The synthesis of mesoporous nanoparticles with controllable structure and organic groups is important for their applications. In this work, yolk-shell-structured periodic mesoporous organosilica (PMO) nanoparticles simultaneously incorporated with ethane-, thioether-, and benzene-bridged moieties are successfully synthesized. The preparation of the triple-hybridized PMOs is via a cetyltrimethylammonium bromide-directed sol-gel process using mixed bridged silsesquioxanes as precursors and a following hydrothermal treatment. The yolk-shell-structured triple-hybridized PMO nanoparticles have large surface area (320 m(2) g(-1) ), ordered mesochannels (2.5 nm), large pore volume (0.59 cm(3) g(-1) ), uniform and controllable diameter (88-380 nm), core size (22-110 nm), and shell thickness (13-45 nm). In vitro cytotoxicity, hemolysis assay, and histological studies demonstrate that the yolk-shell-structured triple-hybridized PMO nanoparticles have excellent biocompatibility. Moreover, the organic groups in the triple-hybridized PMOs endow them with an ability for covalent connection of near-infrared fluorescence dyes, a high hydrophobic drug loading capacity, and a glutathione-responsive drug release property, which make them promising candidates for applications in bioimaging and drug delivery.

A MoS2-based system for efficient immobilization of hemoglobin and biosensing applications.

A novel hydrogen peroxide (H2O2) and nitric oxide (NO) biosensor was fabricated by immobilizing hemoglobin (Hb) on a gold nanoparticle-decorated MoS2 nanosheet (AuNPs@MoS2) nanocomposite film modified glass carbon electrode. The AuNPs@MoS2 nanocomposite not only made the immobilized Hb keep its native biological activity but also facilitated the electron transfer between electrode and the electroactive center of Hb due to its excellent conductivity and biocompatibility. The direct electrochemistry and bioelectrocatalytic activity of Hb were investigated by cyclic voltammetry (CV). The modified electrode showed good electrocatalytic ability toward the reduction of H2O2 and NO. Under optimal conditions, the current response was linear with the concentration of H2O2 and NO in the range from 10 to 300 µM and 10 to 1100 µM with a detection limit of 4 and 5 µM, respectively. This MoS2-based biosensor was sensitive, reproducible and stable, indicating that AuNPs@MoS2 nanocomposite maybe a promising platform to construct electrochemical sensors for chemical and biological molecules detection.

H2O2/acid self-supplying double-layer electrospun nanofibers based on ZnO2 and Fe3O4 nanoparticles for efficient catalytic therapy of wound infection.

Catalytic therapy based on nanozymes is promising for the treatment of bacterial infections. However, its therapeutic efficacy is usually restricted by the limited amount of hydrogen peroxide and the weak acidic environment in infected tissues. To solve these issues, we prepared polyvinyl alcohol (PVA)-polyacrylic acid (PAA)-iron oxide (Fe3O4)/polyvinyl alcohol (PVA)-zinc peroxide (ZnO2) double-layer electrospun nanofibers (PPF/PZ NFs). In this design, PVA serves as the carrier for ZnO2 nanoparticles (NPs), Fe3O4 NPs, and PAA. The double-layer structure of nanofibers can spatially separate the PAA and ZnO2 to avoid their reaction with each other during preparation and storage, while in the wet wound bed, PVA can dissolve and PAA can provide H+ ions to promote the generation of hydrogen peroxide and subsequent conversion to hydroxyl radicals for bacteria killing. In vitro experimental results demonstrated that PPF/PZ NFs can reduce the methicillin-resistant Staphylococcus aureus by 3.1 log (99.92%). Moreover, PPF/PZ NFs can efficiently treat the bacterial infection in a mouse wound model and promote wound healing with negligible toxicity to animals, indicating their potential use as "plug-and-play" antibacterial wound dressings. This work provides a novel strategy for the construction of double-layer electrospun nanofibers as catalytic wound dressings with hydrogen peroxide/acid self-supplying properties for the efficient treatment of bacterial infections.

Metabolic Modulation-Mediated Antibiotic and Immune Activation for Treatment of Chronic Lung Infections.

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.

Ultrasound-responsive gallium protoporphyrin and oxygen loaded perfluoropentane nanodroplets for effective sonodynamic therapy of implant infections.

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

Recent Advances in DNA Nanotechnology-Enabled Biosensors for Virus Detection.

Virus-related infectious diseases are serious threats to humans, which makes virus detection of great importance. Traditional virus-detection methods usually suffer from low sensitivity and specificity, are time-consuming, have a high cost, etc. Recently, DNA biosensors based on DNA nanotechnology have shown great potential in virus detection. DNA nanotechnology, specifically DNA tiles and DNA aptamers, has achieved atomic precision in nanostructure construction. Exploiting the programmable nature of DNA nanostructures, researchers have developed DNA nanobiosensors that outperform traditional virus-detection methods. This paper reviews the history of DNA tiles and DNA aptamers, and it briefly describes the Baltimore classification of virology. Moreover, the advance of virus detection by using DNA nanobiosensors is discussed in detail and compared with traditional virus-detection methods. Finally, challenges faced by DNA nanobiosensors in virus detection are summarized, and a perspective on the future development of DNA nanobiosensors in virus detection is also provided.

On-Demand Free Radical Release by Laser Irradiation for Photothermal-Thermodynamic Biofilm Inactivation and Tooth Whitening.

Dental diseases associated with biofilm infections and tooth staining affect billions of people worldwide. In this study, we combine photothermal agents (MoS2@BSA nanosheets, MB NSs), a thermolysis free-radical initiator (AIPH), and carbomer gel to develop laser-responsive hydrogel (MBA-CB Gel) for biofilm inactivating and tooth whitening. Under a physiological temperature without laser irradiation, MB NSs can eliminate free radicals generated from the slow decomposition of AIPH due to their antioxidative activity, thereby avoiding potential side effects. A cytotoxicity study indicates that MB NSs can protect mammalian cells from the free radicals released from AIPH without laser irradiation. Upon exposure to laser irradiation, MB NSs promote the rapid decomposition of AIPH to release free radicals by photothermal effect, suggesting their on-demand release ability of free radicals. In vitro experimental results show that the bacteria inactivation efficiency is 99.91% (3.01 log units) for planktonic Streptococcus mutans (S. mutans) and 99.98% (3.83 log units) for planktonic methicillin-resistant Staphylococcus aureus (MRSA) by the mixed solution of MB NSs and AIPH (MBA solution) under 808 nm laser irradiation (1.0 W/cm2, 5 min). For S. mutans biofilms, an MBA solution can inactivate 99.97% (3.63 log units) of the bacteria under similar laser irradiation conditions. Moreover, MBA-CB Gel can whiten an indigo carmine-stained tooth under laser irradiation after 60 min of laser treatment, and the color difference (ΔE) in the teeth of the MBA-CB Gel treatment group was 10.9 times that of the control group. This study demonstrates the potential of MBA-CB Gel as a promising platform for biofilm inactivation and tooth whitening. It is worth noting that, since this study only used stained models of extracted teeth, the research results may not fully reflect the actual clinic situation. Future clinical research needs to further validate these findings.

Self-Adaptive Antibiofilm Effect and Immune Regulation by Hollow Cu2MoS4 Nanospheres for Treatment of Implant Infections.

Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow Cu2MoS4 nanospheres (H-CMS NSs) with pH-responsive enzyme-like activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.

Nanotherapeutics with immunoregulatory functions for the treatment of bacterial infection.

The advent of drug-resistant pathogens results in the occurrence of stubborn bacterial infections that cannot be treated with traditional antibiotics. Antibacterial immunotherapy by reviving or activating the body's immune system to eliminate pathogenic bacteria has confirmed promising therapeutic strategies in controlling bacterial infections. Subsequent studies found that antimicrobial immunotherapy has its own benefits and limitations, such as avoiding recurrence of infection and autoimmunity-induced side effects. Current studies indicate that the various antibacterial therapeutic strategies inducing immune regulation can achieve superior therapeutic efficacy compared with monotherapy alone. Therefore, summarizing the recent advances in nanomedicine with immunomodulatory functions for combating bacterial infections is necessary. Herein, we briefly introduce the crisis caused by drug-resistant bacteria and the opportunity for antibacterial immunotherapy. Then, immune-involved multimodal antibacterial therapy for the treatment of infectious diseases was systematically summarized. Finally, the prospects and challenges of immune-involved combinational therapy are discussed.

Amylase degradation enhanced NIR photothermal therapy and fluorescence imaging of bacterial biofilm infections.

Effective treatment of bacterial biofilm-related infections is a great challenge for the medical community. During the formation of biofilms, bacteria excrete extracellular polymeric substances (EPS), including polysaccharides, proteins, nucleic acids, etc., to encapsulate themselves and form a "fort-like" structure, which greatly reduces the efficiency of therapeutic agents. Herein, we prepared a nanoagent (MnO2-amylase-PEG-ICG nanosheets, MAPI NSs) with biofilm degradation capability for efficient photothermal therapy and fluorescence imaging of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections. MAPI NSs were constructed by sequentially modifying α-amylase, polyethylene glycol (PEG), and indocyanine green (ICG) on manganese dioxide nanosheets (MnO2 NSs). Experimental results exhibited that MAPI NSs could accumulate in infected tissues after intravenous injection, degrade in the acidic biofilm microenvironment, and release the loaded ICG for near-infrared (NIR) fluorescence imaging of the infected tissues. Importantly, MAPI NSs could efficiently eliminate MRSA biofilm infections in mice by α-amylase enhanced photothermal therapy. In addition, MAPI NSs exhibited neglectable toxicity towards mice. Given the superior properties of MAPI NSs, the enzyme-degradation enhanced therapeutic strategy presented in this work offers a promising solution for effectively combating biofilm infectious diseases.

Environment-Responsive Therapeutic Platforms for the Treatment of Implant Infection.

The application of medical implants has greatly improved the survival rate and life quality of patients. Nevertheless, in recent years, there are increasing cases of implant dysfunction or failure because of bacterial infections. Despite significant improvements in biomedicine, there are still serious challenges in the treatment of implant-related infections. With the formation of bacterial biofilms and the development of bacterial resistance, these limitations lead to a low efficacy of conventional antibiotics. To address these challenges, it is urgent to exploit innovative treatment strategies for implant-related infections. Based on these ideas, environment-responsive therapeutic platforms with high selectivity, low drug resistance, and minor dose-limiting toxicity have attracted widespread attention. By using exogenous/endogenous stimuli, the antibacterial activity of therapeutics can be activated on demand and exhibit remarkable therapeutic effects. Exogenous stimuli include photo, magnetism, microwave, and ultrasound. Endogenous stimuli mainly include the pathological characteristics of bacterial infections such as acidic pH, anomalous temperature, and abnormal enzymatic activities. In this review, the recent progress of environment-responsive therapeutic platforms with spatiotemporally controlled drug release/activation is systematically summarized. Afterward, the limitations and opportunities of these emerging platforms are highlighted. Finally, it is hoped that this review will offer novel ideas and techniques to combat implant-related infections.

Endogenous/Exogenous Nanovaccines Synergistically Enhance Dendritic Cell-Mediated Tumor Immunotherapy.

Traditional dendritic cell (DC)-mediated immunotherapy is usually suppressed by weak immunogenicity in tumors and generally leads to unsatisfactory outcomes. Synergistic exogenous/endogenous immunogenic activation can provide an alternative strategy for evoking a robust immune response by promoting DC activation. Herein, Ti3 C2 MXene-based nanoplatforms (termed MXP) are prepared with high-efficiency near-infrared photothermal conversion and immunocompetent loading capacity to form endogenous/exogenous nanovaccines. Specifically, the immunogenic cell death of tumor cells induced by the photothermal effects of the MXP can generate endogenous danger signals and antigens release to boost vaccination for DC maturation and antigen cross-presentation. In addition, MXP can deliver model antigen ovalbumin (OVA) and agonists (CpG-ODN) as an exogenous nanovaccine (MXP@OC), which further enhances DC activation. Importantly, the synergistic strategy of photothermal therapy and DC-mediated immunotherapy by MXP significantly eradicates tumors and enhances adaptive immunity. Hence, the present work provides a two-pronged strategy for improving immunogenicity and killing tumor cells to achieve a favorable outcome in tumor patients.