Understanding the mechanisms of virus infection is pivotal for the effective prevention and treatment of viral diseases. This review provides a comprehensive overview of the latest advancements in realtime monitoring of viral dynamics within established infection models. We begin by summarizing the recent progress in fluorescent probe and labeling techniques for real-time and in situ virus tracking. Next, we provide an in-depth analysis of the types and characteristics of virus infection models and discuss their respective advantages and limitations in virus tracking. Finally, we detail the recent progress in viral dynamics tracking across different infection models, illustrating how to use these models to monitor virus infection dynamics and discussing the meaningful biological information that can be acquired. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Idiopathic pulmonary fibrosis (IPF), a progressive, life-threatening disease marked by excessive collagen deposition, severe tissue injury, and dysregulated oxidative stress, poses a major threat to human health. Despite clinical advances, current therapies have limited anti-fibrotic efficacy. Here we show a reactive oxygen species (ROS)-responsive nanosystem targeting tissue inhibitor of metalloproteinase-1 (TIMP-1) for spatiotemporally precise IPF treatment. Anti-TIMP-1 antibodies (aT) are conjugated to mesenchymal stem cell-derived exosomes (Mexo) via ROS-cleavable phenylboronic acid ester linkers (cl), yielding Mexo-cl-aT. Following intratracheal administration, cl linkers are selectively cleaved by elevated ROS in the IPF microenvironment, enabling ROS scavenging while releasing Mexo and aT to mediate tissue repair and collagen degradation, respectively. We demonstrate that a single dose of Mexo-cl-aT exerts robust therapeutic efficacy against IPF in a bleomycin-induced mouse model of advanced-stage fibrosis, thereby validating this nanosystem as a safe and efficient candidate for next-generation IPF therapies.

The immunosuppressive tumor microenvironment (TME), shaped significantly by tumor-associated macrophages (TAMs), facilitates immune escape in cervical cancer. The dynamic post-translational modification O-GlcNAcylation, regulated by O-GlcNAc transferase (OGT), has been implicated in cancer progression, but its specific role in modulating TAM function within the TME remains largely unknown. This study aimed to investigate the impact and mechanism of tumor cell OGT-mediated O-GlcNAcylation on the functional polarization of TAMs and anti-tumor immunity in cervical cancer. We employed a co-culture system of THP-1-derived macrophages and cervical cancer CaSki cells with OGT gain- or loss-of-function manipulation. Macrophage polarization was assessed via flow cytometry (CD86/M1, CD206/M2) and phagocytosis assays. Cytokine secretion profiles were measured by ELISA. The molecular mechanism was explored using co-immunoprecipitation, Western blot, and site-directed mutagenesis of STAT1. OGT overexpression in CaSki cells reprogrammed co-cultured macrophages towards an M2-like phenotype, suppressed their phagocytic capacity, and altered cytokine secretion towards a pro-tumorigenic profile. Mechanistically, OGT directly O-GlcNAcylated STAT1 at serine 727 (Ser727), which competitively inhibited its phosphorylation. Crucially, the immunomodulatory effects of OGT were completely abolished in STAT1-knockout or STAT1 Ser727-mutant CaSki cells. Conversely, pharmacological inhibition of OGT promoted an M1-like macrophage phenotype and enhanced phagocytosis. Our findings reveal a novel immune evasion mechanism in cervical cancer whereby tumor cell OGT, via O-GlcNAcylating and inactivating STAT1 at Ser727, drives TAMs into an immunosuppressive M2-like state. Targeting the OGT/STAT1 axis may represent a promising strategy to reprogram the TME and restore anti-tumor immunity.

Melanoma, the most aggressive form of skin cancer, remains a formidable therapeutic challenge. While oncolytic viruses (OVs) exhibit promising antitumor potential, their efficacy is often limited by insufficient intratumoral viral replication, poor tissue penetration, and the immunosuppressive tumor microenvironment (TME). Herein, a multistage microneedle (MN-OJ) system designed to amplify both local oncolysis and systemic antitumor immunity mediated by oncolytic adenovirus (OA) in melanoma. The dissolvable MN base facilitates rapid OA delivery, inducing tumor cell lysis and subsequent release of tumor-associated antigens to prime T-cell responses. Concurrently, the degradable MN tip enables sustained release of JQ1, which enhances OA replication, modulates lactic acid levels and PD-L1 expression, thereby reprogramming the immunosuppressive TME to promote T-cell infiltration and cytotoxicity. In murine models, MN-OJ demonstrated potent inhibition of both primary and distal tumors, without systemic toxicity. This innovative platform combines immediate tumor destruction with sustained immune modulation, offering a promising clinical approach for melanoma therapy.

In vivo fluorescent in situ visualization of viral infection dynamics is crucial for elucidating the mechanisms of viral pathogenesis. However, current approaches lack sufficient specificity and sensitivity for spatiotemporal monitoring of viral infection in vivo. Here, we proposed virosome-masked ratiometric nanoprobes (VMR-NPs) integrated with dual-stimuli-responsive near-infrared (NIR) Förster resonance energy transfer (FRET) reporters that specifically recognize influenza A virus (IAV) viral RNA (vRNA) and apurinic/apyrimidinic endonuclease 1 (APE1). Surface hemagglutinin (HA) envelope protein of IAV virosome endows VMR-NPs with enhanced host-cell association and IAV-like intracellular trafficking behavior. Following internalization, vRNA recognition together with APE1-assisted signal amplification modulates the ratiometric fluorescence output of VMR-NPs, enabling sensitive detection of infection-associated signal changes in vitro and in vivo. This study establishes an IAV virosome-masked sensing platform for imaging infection-associated IAV burden and provides a useful tool for studying virus-related biological processes.

Biological detection and bioimaging based on specific optical signal changes have succeeded in recent decades. Likewise, a plethora of strategies have emerged to enhance detection sensitivity. Notably, whispering gallery mode (WGM)-based optical biosensing has attracted significant attention due to its high sensitivity and label-free nature. In this review, we present the characterization parameters of WGM resonators in detail and elucidate their relationship with ultrasensitive biological detection and bioimaging. Then, we present emerging design principles and functionalization strategies of WGM resonators. Finally, we thoroughly describe the recent advances of WGM-based optical biosensing technology in different biosensing applications. Thus, we aim to offer fresh insights and stimulate interest among researchers from various domains toward developing and utilizing WGM resonators for biosensing purposes.

The activation of stimulator of interferon genes (STING) pathways holds immense potential for cancer immunotherapy. Nevertheless, the challenge lies in achieving precise and efficient STING activation within tumors while avoiding systemic immunotoxicity. Here, we develop a novel nanotherapeutic platform, termed HAL@SyBVs, by simply electroporating FDA-approved prodrug 5-aminolevulinate hydrochloride (HAL) into the synthetic bacterial vesicles (SyBVs), which allows for the spatiotemporal orchestration of STING pathways. Following systemic injection, HAL@SyBVs target tumor tissues, where HAL induces the confined biosynthesis and accumulation of sonosensitizer protoporphyrin IX (PpIX) within mitochondria. Upon ultrasound irradiation, PpIX-induced reactive oxygen species (ROS) trigger the release of double-stranded DNA (dsDNA), thereby achieving precise STING activation. Simultaneously, SyBVs enhance STING signaling by impeding its degradation, thereby amplifying the immune response. This intelligent synergy effectively ameliorates the immunosuppressive tumor microenvironment and elicits a robust antitumor T cell immune response, resulting in comprehensive tumor regression without apparent adverse effects.

Dendritic cell (DC)-based vaccines for solid tumors face major challenges, including limited tumor-specific antigens and immunosuppressive stroma. Here, we present a therapeutic nanovaccine (UCNP@MOF@MI@FM [UMMF]) composed of a DC/tumor fused cytomembrane-coated UCNP@MOF nanoparticle, co-loaded with a MutT homolog 1 (MTH1) inhibitor and combined with tetrahydrobiopterin (BH4). The fused membrane facilitates dual targeting to tumors and lymph nodes while enabling broad-spectrum tumor antigen presentation. Upon near-infrared (NIR) irradiation, upconversion-triggered reactive oxygen species (ROS) generation and MTH1 inhibition synergistically induce immunogenic PANoptosis, releasing antigens and promoting DCs maturation. Simultaneously, ROS remodels the tumor stroma by depleting collagen and cancer-associated fibroblasts, enhancing T cell infiltration. BH4 counteracts IDO-mediated kynurenine accumulation, reversing immune tolerance and restoring T cell function. This multifunctional platform integrates tumor cell killing, immune priming, and stromal reprogramming, resulting in robust antitumor immunity, reduced relapse, and metastasis suppression. UMMF offers a promising strategy for precision nanoimmunotherapy through controlled PANoptosis and microenvironment modulation.

Background Legumain is a ubiquitously expressed protease playing vital parts in multiple pathological conditions, such as cancerous and inflammatory diseases including pancreatitis, fibrosis and atherosclerosis. The multiple links between legumain and various disease may derive from its role in immune cell infiltration and antigen presenting process. Despite its established clinical associations, the mechanistic interplay between legumain mediated immune cross-talk and disease pathogenesis remains poorly understood. However, there are very limited real-time legumain probes reported. The fact emphasizes the importance of developing legumain-specific fluorescent probe, particularly in leukocytes such as macrophages. Results First, a series legumain-specific AIE-peptide probes have been developed and applied for the real-time fluorescent imaging of legumain in subphenotypes of macrophages. Human macrophages were derived from THP-1 cells and induced into M0, M1 and M2 macrophage, which was validated by flow cytometry by recognizing the fluorescent labeled surface markers. The probes showed significant real-time fluorescent turn-on upon legumain, which is useful for further investigation of inflammatory diseases. The good selectivity of the probes was proved by legumain inhibitor and immunofluorescence staining. In addition, by proper design, targeted legumain imaging in M2 macrophages can also be achieved. It is also noteworthy that the probes exert minimal disturbance to the cytoskeleton of macrophages, which indicates their good compatibility in sustaining the normal biological functions of macrophages. Significance The probes have successfully realized the specific legumain sensing in human macrophages, both for any subphenotype or for targeted imaging in M2 macrophages. It is also noteworthy that the probes exerted minimal side effects on the cytoskeleton morphology of macrophages, which will benefit the fluorescent sensing of targets which levels are sensitive to the probe disturbance.

Small extracellular vesicles (sEVs) are nanosized vesicles. Death receptor 5 (DR5) mediates extrinsic apoptosis. We engineer DR5 agonistic single-chain variable fragment (scFv) expression on the surface of sEVs derived from natural killer cells. PDGFR transmembrane domain delivers DR5-scFvs to the surface of sEVs. DR5-scFv sEVs rapidly induce apoptosis of different types of DR5 + cancer cells, myeloid-derived suppressor cells (MDSCs), and cancer-associated fibroblasts (CAFs). DR5-scFv sEVs migrate specifically to DR5 + tumors in vitro and in vivo. Systemic delivery of DR5-scFv sEVs significantly inhibits the growth of DR5 + melanoma, liver cancer, and breast cancer and prolongs mouse life span without significant toxicity. DR5-scFv sEVs are significantly more efficacious than DR5 antibodies in vivo. In organotypic patient-derived melanoma slice cultures, DR5-scFv sEVs effectively inhibit melanoma cells and MDSCs and activate CD8 + T cells. Our studies demonstrate that DR5-scFv sEVs can inhibit tumor growth by targeting tumor cells and immunosuppressive stromal cells in the TME.

BACKGROUND:Targeted drug delivery systems have garnered increasing research interest in cancer threapy. Bacteria have emerged as a promising vehicle due to their innate ability to the tumour microenvironment (TME) and their intrinsic immune-stimulating properties. This review explores the application of bacteria in oncology, emphasizing the tumour-targeting behaviour of specific strains, their immunomodulatory functions, and their potential as delivery platforms for the controlled release of therapeutic agents. MAIN TEXT:This review synthesizes recent advances in bacteria-mediated cancer therapy, focusing on the mechanisms underlying bacterial targeting of hypoxic and immunosuppressive regions within the tumor microenvironment (TME). We discuss how genetic modification has been employed to design recombinant bacterial strains with enhanced tumor specificity and amplified therapeutic effects. Furthermore, the integration of bacteria with nanotechnology has facilitated the development of hybrid systems capable of targeted drug delivery and triggered-release mechanisms. The combination of bacterial therapy with other treatment modalities-such as photodynamic (PDT) and sonodynamic therapies (SDT)-is also examined, emphasizing their synergistic potential in overcoming tumor heterogeneity and enhancing anti-tumor immunity. Finally, we survey the current clinical progress of bacteria-based therapeutics and offer perspectives on the future role of artificial intelligence (AI) in improving the design and application of these living medicines. CONCLUSIONS:Bacteria-based delivery systems represent a multifunctional and innovative strategy in the evolution of targeted cancer therapies. Through genetic modification and nanobiotechnology approaches, bacteria can be customized to mediate multi-effect synergistic treatments for cancer, enhancing the precision, safety, and efficacy of cancer therapies. With the ongoing integration of advanced technologies, including AI, there is great potential to overcome existing limitations and accelerate the clinical translation of bacterial anticancer therapies. This interdisciplinary effort is poised to open new avenues for next-generation cancer treatments and lay the foundation for future directions in cancer research and therapeutic practice. KEY POINTS:Bacteria exhibit inherent tumour-targeting capabilities, particularly thriving in hypoxic tumour microenvironments (TMEs) and activating potent anti-tumour immune responses through pathogen-associated molecular patterns (PAMPs) and immunomodulation. Genetic engineering and nanobiotechnology enable advanced bacterial therapies, allowing for reduced toxicity, controlled proliferation, targeted drug delivery and the expression of therapeutic payloads (e.g., cytokines, enzymes, tumour antigens) within tumours. Bacteria serve as versatile platforms for multi-modal synergistic therapy, effectively combining with immunotherapy, photodynamic therapy (PDT), thermodynamic therapy (TDT), photothermal therapy (PTT) and sonodynamic therapy (SDT) to significantly enhance tumour eradication. Artificial intelligence (AI) is poised to revolutionise bacterial cancer therapy, offering powerful tools for optimising synthetic biology designs (e.g., promoters, gene circuits), nanocarrier engineering and predicting bacterial-host interactions for more effective and safer treatments.

Chimeric antigen receptor (CAR) T cell therapies have poor efficacy in solid tumors due to limited target specificity and an immunosuppressive tumor microenvironment. We investigated death receptor 5 (DR5) as a CAR target based on its high expression in both solid tumors and myeloid- derived suppressor cells (MDSCs). We engineered agonistic DR5-specific CAR constructs and evaluated their activity in multiple models, demonstrating DR5-expression-dependent tumor killing, confirmed by knockout and overexpression experiments. DR5-targeting single-chain variable fragments retained their pro-apoptotic activity when expressed on non-effector cells or extracellular vesicles. Among multiple CAR designs, we identified a construct with optimized binding affinity that maintained T cell viability while preserving strong tumor and MDSC-killing potency. To assess safety and efficacy in an immunocompetent setting, we also developed a murine DR5-targeted CAR. In multiple xenograft and syngeneic mouse models, DR5 CAR-T cells reduced tumor growth, prolonged survival, and did not cause detectable toxicity. In patient- derived organoids and tissue slices, DR5 CAR-T cells infiltrated tumor tissues, reduced MDSCs, boosted CD8+ T cell activity, and inhibited tumor growth. These findings support DR5-targeted CAR-T therapy as a promising strategy for treating solid tumors, which combines direct tumor cytotoxicity with immune activation and minimizes off-target effects. Teaser DR5 CAR-T cells eliminate tumor cells and MDSCs and activate tumor-resident CD8+ T cells within the TME. ### Competing Interest Statement HW, SL, and XX are inventors on a patent application related to methods of DR5-CAR T cell-based therapy (provisional patent) on behalf of the University of Pennsylvania. XX reports grant support from Incytes and founders stock and member of the SAB with CureBiotech, Exio Bioscience, TLR Biosciences, and Evinacel Therapeutics. CHJ reports royalties from Novartis paid by the University of Pennsylvania, grant support and personal fees from Kite Gilead, and founders stock and member of the SAB with Dispatch Bio, Capstan Therapeutics, and BlueWhale Bio. TM received an honorarium for participating in the Scientific Advisory Board from Merck, BMS, and Pfizer. The other authors declare no competing interests. National Institutes of Health, https://ror.org/01cwqze88, CA258113, CA261608, CA284182, and CA114046

Tumor cell-derived extracellular vesicles (tEVs) have garnered significant attention as promising antigen delivery vehicles for the development of cancer vaccines. However, their practical applications are hindered by weak immunogenicity and inadequate lymph node targeting. In this study, we engineered tEVs into “self-adjuvant” multiantigenic nanovaccines that simultaneously accumulate in tumors and lymph nodes (LNs), effectively triggering innate and adaptive immunity capable of recognizing both tumor cells and virus antigen-modified tumor cells to inhibit tumor progression. 4T1 tumor cells were infected with vesicular stomatitis virus (VSV), leading to the expression of VSVG and calreticulin (CRT) on their surface. Using these infected cells, we prepared extracellular vesicles (vEVs) carrying both VSVG and CRT. When injected subcutaneously, vEVs targeted tumors effectively due to the homologous targeting capability of tumor cell membranes. In which, VSVG induced fusion between vEVs and tumor cells, creating viral antigen-decorated tumor cells, which enhanced the recognition and phagocytosis of tumor cells by macrophages. Additionally, the surface CRT of vEVs activated the “eat-me” signaling, thus improving their recognition and uptake by dendritic cells (DCs). This led to DC maturation and the activation of antiviral and antitumor T cells, synergistically inhibiting tumor growth. This research introduces a straightforward yet efficacious methodology for the production of cancer vaccines to fight cancer through the stimulation of both the antiviral and antitumor immune responses within the body.

Chimeric antigen receptor (CAR) T cell therapies have poor efficacy in solid tumors due to limited target specificity and an immunosuppressive tumor microenvironment. We investigated death receptor 5 (DR5) as a CAR target based on its high expression in both solid tumors and myeloid-derived suppressor cells (MDSCs). We engineered agonistic DR5-specific CAR constructs and evaluated their activity in multiple models, demonstrating DR5 expression-dependent tumor killing, confirmed by knockout and overexpression experiments. DR5-targeting single-chain variable fragments retained their pro-apoptotic activity when expressed on non-effector cells or extracellular vesicles. Among multiple CAR designs, we identified a construct with optimized binding affinity that maintained T cell viability while preserving strong tumor and MDSC killing potency. To assess safety and efficacy in an immunocompetent setting, we also developed a murine DR5-targeted CAR. In multiple xenograft and syngeneic mouse models, DR5 CAR-T cells reduced tumor growth, prolonged survival, and did not cause detectable toxicity. In patient-derived organoids and tissue slices, DR5 CAR-T cells infiltrated tumor tissues, reduced MDSCs, boosted CD8+ T cell activity, and inhibited tumor growth. These findings support DR5-targeted CAR-T therapy as a promising strategy for treating solid tumors, combining direct tumor cytotoxicity with immune activation while minimizing off-target effects.

Historically, the classification of mesoionic compounds has been disconcerting, with more confusion arising when these molecules are used as ligands for metal complexes. Many mesoionic compounds are also biologically active and widely used in various therapeutic applications, but mesoionic metal complexes have not seen much prevalence in the field. In this work, we determine the "mesoionic" nature of an unusual and rare series of N^S biscyclometallated iridium(iii) complexes [Ir(N^C)2(p-ttqt)] (p-Httqt = 1-phenyl-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-1-ium-2-thiolate; HN^C = 2-phenylpyridine (Hppy) (1), 7,8-benzoquinoline (Hbzq) (2), 2-phenylbenzothiazole (Hbt) (3) and 2-(1-naphthyl)benzothiazole (Hbsn) (4)) as photodynamic therapy (PDT) agents and immunogenic cell death (ICD) inducers. X-ray, infrared spectroscopy and density functional theory studies demonstrate that the mesoionic nature is retained in the iridium(iii) complexes. These complexes are ideal PDT agents with no cytotoxicity at micromolar concentrations (IC50,dark > 25 μM), remarkable photocytotoxicity at nanomolar concentrations and PI values (IC50,light = 1.5-69 nM; PI = 362-33 333), and exquisite selectivity towards cancer cells. Furthermore, their localisation in the endoplasmic reticulum (ER) and efficient reactive oxygen species (ROS) generation enable them to act as photoactivated type II ICD inducers.

Tumor-associated macrophages (TAMs) play dual roles in tumor progression. TAMs are known to induce programmed death ligand-1 (PD-L1) expression in cancer cells. However, the regulatory effects of PD-L1 in melanoma cells on TAM phenotypical switching remain underexplored. Herein, our findings indicated that CD163 and MRC1 levels were significantly elevated in metastatic melanomas compared with primary melanomas, correlating with CD274 expression and predicted patient clinical outcomes. To study the mechanisms regulating M2-like polarization, PD-L1 was knocked out in both YUMM1.7 and B16-F10 melanoma cells. The data revealed that knocking out PD-L1 (PD-L1KO) in melanoma resulted in a decelerated in vivo growth rate, accompanied by a significantly increased M1/M2 ratio, more dendritic cells, and enhanced activation of CD8+ T cells compared with wild-type (WT) melanoma cells. These alterations were associated with decreased expression of M2-associated chemokines (CCL2, CCL3, and CXCL2) and cytokines (IL6, IL10, and TGFβ1). Mice harboring PD-L1KO melanomas exhibited elevated levels of CD8+ T cells in both the tumor-draining lymph nodes and the bloodstream compared with mice with PD-L1WT melanomas. Treatment with extracellular vesicles (EVs) derived from PD-L1KO melanoma resulted in a reduced tumor growth rate and fewer M2-like macrophages in the tumors compared with EVs from PD-L1WT melanomas. Therefore, our data suggest that PD-L1 in melanoma and melanoma-derived EVs induces M2-like polarization, contributing to local and regional immune suppression.

Background: Limited data are available regarding the current microbiological characteristics of extracorporeal membrane oxygenation (ECMO)-related infections in intensive care units (ICUs) in China. This retrospective study aimed to determine the epidemiology, risk factors and impact on the outcome of ECMO-related infections. Methods: A retrospective observational study from January 2014 to December 2019 was performed, and adult patients receiving ECMO support for more than 48 hours were included in this study. The primary outcome was the incidence rate of ECMO-related infection. Clinical data were recorded, and risk factors associated with an increased risk of ECMO-related infection were analyzed. Results: A total of 174 adult patients who received ECMO and underwent ECMO for 1,670 days were included in this study. Forty-six patients (26.4%) developed ECMO-related infections, corresponding to 27.5 first episodes/1,000 ECMO days. The most common ECMO-related infection observed was ventilatorassociated pneumonia (VAP). Infected patients had longer durations of mechanical ventilation {20.2 8.1, 17.3) vs. 7.6 (IQR, 5.6, 9.7) days, P<0.001] and hospital stays (28.2 +/- 20.7 vs. 22.0 +/- 15.6 days, P<0.001). The factors independently associated with ECMO-related infection were a dynamic decrease in lymphocyte count [adjusted odds ratio (OR) =3.578, 95% confidence interval (CI): 2.175-4.906, P<0.001] and ECMO duration (adjusted OR =1.207, 95% CI: 1.096-1.330, P<0.001). Compared to patients without infection, infected patients had greater hospital mortality (39.1% vs. 78.3%, P<0.001) and 90-day mortality (40.6% vs. 87.0%, P<0.001). ECMO-related infections were associated with worse outcomes (adjusted Kaplan-Meier curve, log rank test P<0.001). Conclusions: Patients supported by ECMO had a high risk of developing ECMO-related infection. The most common ECMO-related infection observed was VAP. A dynamic decrease in lymphocyte counts was significantly associated with an increased risk of ECMO-related infection.

Tumor-associated macrophages (TAMs) play dual roles (both pro- and antitumor) in tumor progression. TAMs induce programmed death ligand-1 (PD-L1) expression in cancer cells. However, the regulatory effects of PD-L1 in melanoma cells on TAM phenotypical switching remain underexplored. Herein, CD163 and MRC1 levels were significantly elevated in metastatic melanomas compared with those in primary melanomas, correlating with CD274 expression and predicted patient clinical outcomes. To study the mechanisms regulating M2-like polarization, PD-L1 was knocked out in both YUMM1.7 and B16-F10 melanoma cells. Knocking out PD-L1 (PD-L1KO) in melanoma resulted in a decelerated in vivo growth rate, accompanied by a significantly increased M1/M2 ratio, more dendritic cells, and enhanced activation of CD8+ T cells compared with wild-type (WT) melanoma cells. These alterations were associated with decreased expression of M2-associated chemokines (CCL2, CCL3, and CXCL2) and cytokines (IL6, IL10, and TGFB1). Mice harboring PD-L1KO melanomas exhibited elevated levels of CD8+ T cells in both the tumor-draining lymph nodes and the bloodstream compared with mice with PD-L1WT melanomas. Treatment with extracellular vesicles (EVs) derived from PD-L1KO melanoma resulted in a reduced tumor growth rate and fewer M2-like macrophages in the tumors compared with EVs from PD-L1WT melanomas. Therefore, these data suggest that PD-L1 in melanoma and melanoma-derived EVs induces M2-like polarization, contributing to local and regional immune suppression.

Infectious diseases severely threaten human health, and traditional treatment techniques face multiple limitations. As an important component of immune cells, macrophages display unique biological properties, such as biocompatibility, immunocompatibility, targeting specificity, and immunoregulatory activity, and play a critical role in protecting the body against infections. The macrophage membrane-coated nanoparticles not only maintain the functions of the inner nanoparticles but also inherit the characteristics of macrophages, making them excellent tools for improving drug delivery and therapeutic implications in infectious diseases (IDs). In this review, we describe the characteristics and functions of macrophage membrane-coated nanoparticles and their advantages and challenges in ID therapy. We first summarize the pathological features of IDs, providing insight into how to fight them. Next, we focus on the classification, characteristics, and preparation of macrophage membrane-coated nanoparticles. Finally, we comprehensively describe the progress of macrophage membrane-coated nanoparticles in combating IDs, including drug delivery, inhibition and killing of pathogens, and immune modulation. At the end of this review, a look forward to the challenges of this aspect is presented.

Photodynamic therapy (PDT) has become an important therapeutic strategy because it is highly controllable, effective, and does not cause drug resistance. Moreover, precise delivery of photosensitizers to tumor lesions can greatly reduce the amount of drug administered and optimize therapeutic outcomes. As alternatives to protein antibodies, peptides have been applied as useful targeting ligands for targeted biomedical imaging, drug delivery and PDT. In addition, other functionalities of peptides such as stimuli responsiveness, self-assembly, and therapeutic activity can be integrated with photosensitizers to yield versatile peptide-based nanosystems for PDT. In this article, we start with a brief introduction to PDT and peptide-based nanosystems, followed by more detailed descriptions about the structure, property, and architecture of peptides as background information. Finally, the most recent advances in peptide-based nanosystems for PDT are emphasized and summarized according to the functionalities of peptide in the system to reveal the design and development principle in different therapeutic circumstances. We hope this review could provide useful insights and valuable reference for the development of peptide-based nanosystems for PDT.