Three-dimensional (3D) cell culture using hydrogels offers superb methods to expand cells and study signaling molecules modulating cell behaviors in vitro. However, it is still a great challenge to establish a degradable nonfouling platform for mimicking and simplifying the extracellular matrix (ECM) for cell proliferation and harvest. In this work, a dissociable hydrogel (mXSP) was fabricated, which included the thermosensitive galactose-modified xyloglucan (mXG) network and the zwitterionic network cross-linked by d-sorbitol-responsive phenylboronic ester bonds. The zwitterionic polymers provide hydrogels with an ultralow-fouling property as a nonfouling platform. The temperature/d-sorbitol dual-sensitive networks of the mXSP hydrogels made them easier to dissociate. The mechanical and nonfouling properties, gelation, and degradable behavior of mXSP hydrogels were investigated in detail. Lastly, the efficacy of the mXSP hydrogels for cell expansion and harvest was evaluated. It was demonstrated that the mXSP hydrogels had tunable stiffness and could support robust cell proliferation continuously. Furthermore, expanded cells could be harvested from the mXSP hydrogel with high viability and harvest ratio by adding the biocompatible d-sorbitol solution and adjusting the temperature. To sum up, the cell supporting and releasing mXSP hydrogels as a nonfouling platform provided in this work showed great promise for 3D cell expansion and harvest in vitro.

The extracellular matrix (ECM) is a physical barrier that severely hinders the deep penetration of photothermal agents and immune cells, which is a major challenge to the efficacy of tumor photothermal immunotherapy. In this study, a visible tumor-targeting platelet membrane-wrapped biohybrid vehicle was developed to potentiate photothermalimmunotherapy through cancer-associated fibroblasts (CAFs) reprogramming. This system integrated IR820-modified platelet membrane and manganese-polyphenol nanoparticlesloaded with losartan. Based on the image contrast signals from IR820 and manganese ions, the biohybrid system enabled visual delivery under the guidance of fluorescence-magnetic dual-modal imaging. After reprogramming CAFs to a quiescent state with released losartan, the ECM was remodeled. The attenuated physical barrier and platelet carriers collectively facilitated the deep penetration of photothermal agents, improving the sensitivity of photothermal therapy. Moreover, the synergistic strategy of photothermal stimulation and CAFs regulation simultaneously activated the systemic immunity and alleviated the immunosuppressive tumor microenvironment. The biohybrid delivery system effectively reconstructed the anti-tumor immune defense system to boost the efficacy of photothermal immunotherapy through a positive feedback mechanism. STATEMENT OF SIGNIFICANCE: The dense extracellular matrix (ECM) constitutes a major physical barrier that severely restricts the penetration of photothermal agents and immune cells into tumors, thereby substantially limiting the efficacy of photothermal immunotherapy. A key cause of this barrier is cancer-associated fibroblasts (CAFs), which also suppress immunity. Reverting CAFs to a quiescent state or reprogramming them toward a tumor-suppressive phenotype offers a promising strategy to ameliorate ECM deposition and reverse immunosuppression. A visible tumor-targeting platelet membrane-wrapped biohybrid vehicle was developed to potentiate photothermal-immunotherapy through CAFs reprogramming. This intervention disrupts the stromal barrier and mitigates immune suppression for boosting anti-tumor immunity. Furthermore, the system enables real-time, dual-modal MRI-fluorescence imaging, providing a visual guidance platform for precision photothermal immunotherapy.

Cuproptosis represents a promising avenue for cancer immunotherapy, yet its efficacy is limited by difficulties in achieving targeted mitochondrial copper ion accumulation and upregulating cells reliance on mitochondrial respiration. To address this, we develop a biomimetic copper-based nanoplatform (SCTDM) coated with macrophage-tumor cell hybrid membranes (HM) and co-loaded with the lactate modulator syrosingopine (Su3118) and the copper ionophore disulfiram (DSF). SCTDM integrates active tumor targeting, in situ photothermal therapy (PTT), and lactate metabolism modulation, synergistically enhancing cuproptosis and antitumor immunity. SCTDM releases copper ions and DSF to facilitate mitochondrial copper ions delivery and induce immunogenic cell death (ICD). In the high hydrogen sulfide (H2S) tumor microenvironment (TME), copper ions further form photothermal copper sulfide complexes that enhance PTT efficacy and reactive oxygen species (ROS) generation, thereby augmenting cuproptosis. Notably, the liberated Su3118 selectively inhibits monocarboxylate transporters (MCT1/4), suppressing lactate efflux while simultaneously sensitizing cells to cuproptosis by disrupting glycolysis and restoring mitochondrial respiration. Collectively, the synergistic combination of PTT and lactate metabolism modulation serves to potentiate cuproptosis-induced immunogenic cell death. This cascade effect culminates in the reprogramming of the immunosuppressive TME and augments anti-tumor immunity for eradicating primary tumors and preventing recurrence.

Intratumoral pathogenic bacteria influence tumor progression and affect responses to therapy, however, conventional antibacterial strategies face challenges including antibiotic resistance and nonspecific microbial disruption. Here, we report a NIR-II-responsive nanoplatform (VP-R@PEG-FA) that integrates violet phosphorus nanosheets (VPNSs) with the Toll-like receptor 7 (TLR7) agonist imiquimod (R837) and folate targeting for synergistic photothermal immunotherapy. Under 1064 nm laser irradiation, VP-R@PEG-FA generates localized hyperthermia that simultaneously eradicates tumor cells and intratumoral bacteria. This dual ablation strategy not only eliminates intratumoral pathogenic bacteria but also ingeniously converts them into in situ immunoadjuvants, as bacterial debris releases pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) which acts as an endogenous TLR4 agonist. The combination of bacterially derived TLR4 ligands and nanoparticle-delivered TLR7 agonist R837 induces potent combined immune activation, driving robust maturation of dendritic cells (DCs) and increasing CD8+ T cell infiltration. In 4T1 Triple-negative Breast Cancer (TNBC) models, this approach demonstrates significant primary tumor suppression and, notably, elicits abscopal effects in bilateral tumor models, indicating the enhanced systemic antitumor immunity. This work presents a "waste-to-wealth" strategy that repurposes intratumoral bacteria from immunosuppressive agents into immunostimulants, offering a promising strategy for advancing cancer immunotherapy through rational manipulation of the tumor microenvironment.

Cancer persists as a major global health challenge, marked by high recurrence rates in aggressive malignancies such as melanoma. While immunotherapy has emerged as a promising approach, its clinical benefits are often limited by tumor immune escape mechanisms and an immunosuppressive tumor microenvironment (TME). These hurdles have driven the exploration of integrated approaches, with photothermal-immunotherapy gaining significant traction. In this study, we developed a multifunctional nanoadjuvant (MICN@PI) engineered with an acid-responsive calcium carbonate core, a hypoxia-alleviating MnO2 component, a polydopamine shell for photothermal ablation, and co-loaded immunomodulators (imiquimod and indoximod). The MnO2 in the nanoadjuvant catalytically converted the overexpressed H2O2 in the TME into O2. Concurrently, the combined action of imiquimod and indoximod orchestrated a potent adaptive immune response. Upon near-infrared laser irradiation, MICN@PI achieved significant tumor ablation, inhibited recurrence, and prolonged survival in a murine melanoma model, offering a safe and effective synergistic photothermal-immunotherapy strategy for cancer treatment.

Diabetic wound healing is critically impaired by a pathological microenvironment with two core barriers: circulatory deficits from microangiopathy, and a loss of nanoscale topographical guidance due to extracellular matrix (ECM) disruption. To address this, we developed Musc@CP, an advanced dressing that synergistically combines an ECM-mimetic multi-property scaffold with active vascular modulation. The platform is based on a chitosan-pullulan (CP) nanofibrous scaffold that structurally recapitulates healthy dermal ECM to direct fibroblast adhesion and migration. The matrix incorporates muscone (Musc), a bioactive compound that attenuates intracellular Ca2+ overload-associated endothelial dysfunction and is associated with improved local perfusion. This restoration of blood circulation may contribute to reprogramming the immune microenvironment within the wound, helping to suppress both inflammation and oxidative stress. Consequently, the healing progression in diabetic mice is effectively restored. Together, this integrated strategy represents a promising and mechanistically sound therapy for chronic diabetic wounds.

The pathogenesis of inflammatory bowel disease (IBD) involves a self-perpetuating cycle driven by oxidative stress, microbial dysbiosis, and immune dysregulation. Restoring intestinal microbiota homeostasis and immune balance is therefore critical for intestinal health and long-term disease remission. In this study, an M2 macrophage-based biohybrid system (GaInMg@PDA@M2) was constructed to achieve synergistic intervention against these multiple pathological pathways. This biohybrid system utilized M2 macrophages with inherent inflammatory tropism as delivery vehicles, loaded with multifunctional nanoparticles (GaInMg@PDA) composed of liquid metal (GaIn), magnesium ions (Mg²⁺) and polydopamine (PDA). The nanoparticles effectively scavenged reactive oxygen species and exhibited synergistic antibacterial effects with the GaIn component, while the released Mg²⁺ further promoted macrophage polarization towards the anti-inflammatory M2 phenotype. In a DSS-induced murine colitis model, GaInMg@PDA@M2 demonstrated inflammatory targeting for the diseased colonic tissue and significantly ameliorating clinical symptoms including disease activity index, colon shortening and histopathological damage. The therapeutic mechanisms involved downregulation of pro-inflammatory cytokines, upregulation of anti-inflammatory cytokines, enhancement of antioxidant enzyme activity, restoration of intestinal tight-junction protein expression, and rebalancing of gut microbiota homeostasis. This "cell-homing and multi-effect synergy" strategy represented a precise therapeutic approach capable of disrupting the key pathological cycle in IBD. STATEMENT OF SIGNIFICANCE: Inflammatory bowel disease (IBD) is driven by a self-perpetuating cycle of oxidative stress, microbial dysbiosis, and immune dysregulation, making restoration of intestinal ecosystem balance a major therapeutic challenge. Conventional therapies often lack specificity or fail to address these interconnected pathologies simultaneously, owing to systemic side effects, non-specific immunosuppression, and diminished efficacy over time. In response, a paradigm shift toward a multi-targeted strategy that concurrently tackles oxidative stress, corrects dysbiosis, and resolves inflammation is imperative to break this cycle. To this end, an M2 macrophage-based biohybrid system was developed to achieve synergistic intervention across these key pathological pathways, overcoming the limitations of conventional drugs and enabling simultaneous modulation of multiple core disease mechanisms.

Over the past decade, cancer vaccines have shown great promise in immunotherapy for solid tumors. However, the efficacy of cancer vaccines is unsatisfactory due to the complexity, heterogeneity, and immune evasion of cancer, as well as the instability of the core components of the vaccines (antigens and adjuvants), the weak immunogenicity and low presentation efficiency of antigens, and the inability to effectively activate immune cells. Nanotechnology is considered to be a transformative approach to address these challenges by improving vaccine delivery. As carriers and/or adjuvants, nanoparticles take advantage of their superior physicochemical properties to enhance the stability of antigens and adjuvants, achieve controlled release in time and space, enable flexible and synergistic combination therapies, and create highly targeted delivery systems, thereby optimizing the efficacy and durability of antitumor immunity and minimizing side effects. In this review, the key components of the nanovaccine strategy are highlighted, which covers antigen forms, adjuvant types, nanovaccine platforms, and more. We provide the latest advances in the development of cutting-edge biomaterials and carrier systems for controlled vaccine delivery. Finally, integrating the current progress strategy, we offer critical perspectives on future applications of nanomaterials in cancer vaccines for clinical translation.

The development of vaccine platforms capable of inducing durable immunity remains a crucial frontier. While conventional vaccines offer proven efficacy, their often limited durability poses challenges for rapidly evolving pathogens and cancer immunotherapy. Recent advances in biomaterials and nanotechnology have enabled the rational design of bioengineered nanovaccines. These systems leverage engineered polymeric, lipid-based, and hybrid materials to achieve controlled antigen release, targeted lymph node delivery, and enhanced cross-presentation. Their “bioengineered” functionality allows them to actively orchestrate sustained immune activation. This review examines the immunological foundations of long-term memory, focusing on transcriptional, epigenetic, and metabolic regulation of memory T cell differentiation. Subsequently, it explores material engineering strategies for prolonging antigen availability, refining lymph node targeting, and enhancing antigen presentation. Translational progress in infectious diseases, cancer, and chronic conditions is reviewed, with emphasis on lipid nanoparticle platforms. Finally, we discuss future directions, including intelligent biomaterials, personalized design, safety, and clinical translation pathways, providing a framework for next-generation nanovaccines against evolving global health threats.

Abstract Tumor hypoxia critically drives the development of an immunosuppressive tumor microenvironment (TME) and accelerates tumor progression. Besides, hypoxia seriously restricts O2-dependent reactive oxygen species (ROS) generation, thereby severely compromising the therapeutic efficacy of photodynamic therapy (PDT). To address these challenges, we developed a multifunctional manganese (Mn)-based nanozyme (MLDHI) loaded with indocyanine green (ICG) to reprogram the immunosuppressive TME for potentiated phototherapy combined with immunotherapy. Upon intratumoral injection, the Mn4+ doped within the nanozyme shell catalyzes the decomposition and conversion of overexpressed H2O2 in the tumor tissue into O2, markedly alleviating hypoxia and supplying O2 for ICG-mediated PDT to enhance cytotoxic ROS production. The resulting phototherapeutic efficacy promotes immunogenic cell death (ICD) of tumor cells and releases double-stranded deoxyribonucleic acid (dsDNA), which together with Mn2+ embedded in the lamellar structure synergistically activates the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway, triggering interferon (IFN)-β release and dendritic cell (DC) maturation. In a breast tumor model, a single intratumoral injection of MLDHI plus laser irradiation achieved 75% tumor ablation and elicited robust immune memory to prevent recurrence and metastasis.

Diabetic wounds, prone to infection and delayed healing, represent a major clinical challenge. Traditional nanosilver-based antibacterial agents remain challenging, including complex preparation, tendency to agglomerate, and poor biocompatibility. Herein, we synthesized lactoferrin-silver oxide nanoparticles (LF-Ag2O2 NPs) via a one-step biomimetic mineralization method using lactoferrin (LF) as a dispersant. This approach significantly improved the dispersibility, stability, and biocompatibility of Ag2O2 NPs while enabling synergistic antibacterial activity. Furthermore, we developed a core-shell microneedle patch (LAg&FGF@CP MN) for programmed drug release to achieve sequential treatment of diabetic wounds. The patch employs a layered loading strategy: the shell layer of the microneedle releases LF-Ag2O2 NPs rapidly in the acidic wound microenvironment, generating reactive oxygen species (ROS) and Ag+ that act synergistically with LF to eliminate bacteria efficiently; The inner core layer of the microneedle degrades upon exposure to ROS, slowly releasing fibroblast growth factor (bFGF). This promotes cell proliferation, M2 macrophage polarization, and angiogenesis to facilitate tissue regeneration. This programmed drug delivery system effectively disrupts the "infection-inflammation" vicious cycle and significantly accelerates diabetic wound healing. Collectively, this work offered a novel and efficient strategy for managing refractory diabetic wounds.

The mRNA vaccine for the novel coronavirus disease (COVID-19) has achieved remarkable success, marking the advent of a new era in mRNA vaccine development. To surmount the challenge of mRNA delivery, a range of nanocarriers have been devised for delivering mRNA encoding tumor antigens, cytokines, and other biological entities, which incite the body to generate robust antitumor immune responses. The combination of mRNA vaccines with immune checkpoint blockades (ICBs) has been demonstrated to enhance the treatment efficiency. Furthermore, the combination of mRNA vaccines with immunostimulatory adjuvants has the potential to elicit a more robust immune response. This review presents an overview of the research progress in mRNA delivery by lipid nanoparticles (LNPs), polymeric carriers, and nanocarriers based on cell membrane components. It outlines the efficacy of different contents encoded by mRNA in antitumor therapy and analyzes the mechanism of mRNA vaccine action on innate and adaptive immune responses from the perspective of various immune cells. The prospects of mRNA combination therapy are discussed at the end, aiming to provide new therapeutic strategies for cancer treatment.

Immune adjuvants are extremely important in tumor vaccines, which can amplify antigen-specific immune responses and enhance anti-tumor efficacy. Nevertheless, well-designed adjuvants and rational combination of adjuvants and antigens still remain a challenge in tumor vaccines. In this study, we designed and formulated carrier-free double-adjuvant nanoparticles(FPC-NPs) by self-assembling of fluoroalkane-grafted polyethylenimide(PEI)(Toll-like receptor 4(TLR4) agonist) and cytosine-phosphateguanine(CpG)(TLR9 agonist), and then obtained personalized tumor vaccines(FPC-NPs@TAAs) by electrostatic adsorption of tumor-associated antigens(TAAs) on the surface of FPC-NPs. The results showed that FPC-NPs@TAAs could promote cellular internalization of adjuvants, deliver antigens and adjuvants to the same antigen-presenting cell, which can effectively activate dendritic cells, encourage cross-presentation of antigens, and reduce the proportion of M2-type macrophages. Our work presents a simple method to realize the dual adjuvant combination of TLR4 and TLR9 via well-designed carrier-free nanoparticles, showing great promise for developing personalized tumor vaccines to enhance the efficacy of immunotherapy.

During two-dimensional (2D) culture, stem cells gradually lose their proliferative activity and multipotency due to various physicochemical conditions, which significantly hinder the large-scale clinical applications of stem cell therapy. In recent years, three-dimensional (3D) cell culture has been increasingly utilized in the field of stem cell expansion owing to its unique advantages. The superhydrophilicity of zwitterionic hydrogels ensures the maintenance of stem cells' stemness during their expansion. This study aims to address a key challenge in the large-scale culture of stem cells in vitro: how to sustain their proliferative capacity and multipotency while achieving efficient cell recovery. To this end, we have designed a novel zwitterionic degradable hydrogel based on host-guest interactions as a 3D carrier for the in vitro culture of adipose-derived stem cells (ADSCs). We synthesized the copolymer poly(sulfobetaine-co-cyclodextrin) (p(SBMA-co-CD)) and adamantane-grafted hyaluronic acid (HA-Ada), and a stable hydrogel was rapidly formed by simply mixing solutions of these two polymers. Leveraging the antifouling properties of zwitterionic groups, this hydrogel effectively maintained the long-term stemness expression of ADSCs during culture. More importantly, we utilized the reversibility of host-guest interactions to disrupt the cross-linked structure of the hydrogel by adding competitive monomers, enabling efficient recovery of stem cells under gentle conditions. This process not only achieved a high recovery rate of stem cells but also avoided the damage to cells caused by traditional cell recovery methods. In summary, this study creatively introduced host-guest interactions into a zwitterionic hydrogel and successfully applied it to the 3D culture and recovery of stem cells in vitro. This hydrogel demonstrates functional plasticity in stem cell proliferation, culture, and harvest, holding promise for providing more reliable and efficient solutions in the fields of stem cell therapy and tissue engineering.

The dysregulation of the microglia-neuron axis plays a pivotal role in the pathogenesis of cognitive dysfunction following traumatic brain injury (TBI). The C-C chemokine receptor 5 (CCR5), markedly upregulated on both microglia and neurons post-injury, serves as a crucial mediator in the neuroinflammatory response and consequent neurological deficits. However, the therapeutic application of CCR5 antagonists in TBI is impeded by the delivery barriers presented by the blood-brain barrier (BBB) and their limited neuron-targeting efficacy. In this study, we introduce a novel nasal-to-brain delivery nanoplatform designed to facilitate the efficient brain delivery of DAPTA, a peptide antagonist of CCR5, aiming to inhibit CCR5 signaling and improving cognitive function following TBI. Biocompatible chitosan nanocarriers grafted with cell-penetrating peptide (TAT) and neuron-binding lactoferrin (Lf) were initially fabricated, demonstrating substantial DAPTA loading capacity, active mucosal and neural transportation, and enhanced neuron-targeting capabilities. The dual-engineered nanodrugs (DA@LT NPs) effectively penetrated the trigeminal and olfactory nerves, significantly enhancing the transport of DAPTA into the brain following intranasal delivery. In a TBI-induced mouse model, DA@LT NPs markedly alleviated the neuroinflammatory response, promoted M2 microglia polarization, protected neurons from pyroptosis, and improved both motor and cognitive functions of animals. The non-invasive intranasal delivery of the therapeutic CCR5 peptide antagonist using these mucus-penetrating and neuron-targeting nanoformulations presents a promising intervention for ameliorating neurological inflammation and cognitive impairments associated with TBI.

Triple-negative breast cancer (TNBC) exhibits low response rates to current immunotherapies. In this study, we present a double-layer dissolvable microneedle (MN) patch consisting of chemotherapeutic drugs in the shell layer and a carrier-free nanoadjuvant in the core for boosted chemo-immunotherapy. The rapid release of doxorubicin (DOX) elicits immunogenic cell death (ICD) to induce the production of tumor-associated antigens (TAAs). Subsequently, the carrier-free nanoadjuvants are sustainably released for capturing TAAs and generating personalized nanovaccines in situ. The controlled, on-demand biphasic release of chemodrug and nanoadjuvant is proved highly effective in suppressing the growth of tumors and potentiating the antitumor immune response. Ultimately, combining MN patches and antiprogrammed cell death protein-1 (aPD-1) results in a more pronounced therapeutic response. Our work introduces a double-layer detachable MN patch as an implanted microreservoir for copackaging and biphasic release of drugs with distinct therapeutic effects, offering a promising avenue for advanced synergistic immunotherapy.

Due to the utilization of well-defined artificial niches, stem cell culture in a three-dimensional hydrogel matrix has been a promising method for obtaining sufficient seed cells. Although various hydrogels can support desirable cell proliferation, establishing a normalized hydrogel that adequately mimics the extracellular matrix (ECM), maintains stemness and allows for controlled release of stem cells remains a significant challenge. Herein, we report a hydrogel composed of sulfobetaine-modified dextran and gelatin to maintain stemness and enable the rapid release of adipose-derived stem cells (ADSCs). Dextran can effectively maintain multipotent phenotype of ADSCs by grafting zwitterionic groups. Gelatin can significantly improve the proliferation of ADSCs. The hydrogel network they form effectively mimics the ECM microenvironment, providing an advantage when used as a three-dimensional niche to promote cell proliferation. Most importantly, the disulfide-crosslinked hydrogels show specific photodegradation capability, which precisely enables the system to achieve controlled release and efficient harvest of ADSCs. The cell viability (90 %) and harvest ratio (64 %) were well maintained by light degradation compared with GSH and collagenase degradation. Overall, this study offers a universal stem cell niche based on photodegradable hydrogel that shows great promise in the field of ADSCs proliferation and harvest.

The key to achieving synergistic ferroptosis immunotherapy is enhancing the iron content in tumor cells, improving specific immunity, and regulating the tumor microenvironment. In this study, a drug-free biohybrid system targeting ferritin is developed using M1 macrophage microvesicles and HKN15-modified Prussian blue nanoparticles for synergistic ferroptosis immunotherapy. HKN15-modified nanoparticles simultaneously enhance iron content by activating endogenous iron ions and replenishing exogenous iron ions, which disrupts iron homeostasis for inducing ferroptosis in tumor cells. Photothermally enhanced ferroptosis based on Prussian blue nanoparticles also stimulates dendritic cell maturation. Moreover, M1 vesicles and iron ions from Prussian blue nanoparticles promote macrophage polarization to improve specific immunity. The mutual promotion of ferroptosis and antitumor immunity effectively results in a synergistic therapeutic circuit for inhibiting tumor growth and preventing cancer recurrence and metastasis in 4T1 tumor-bearing female mice, thus offering a promising strategy for drug-free biohybrid system-mediated ferroptosis immunotherapy.

Chimeric antigen receptor T cells (CAR-T) immunotherapy has achieved remarkable progress in the treatment of hematological malignancies. However, it encounters challenges including complex manufacturing processes, high cost, and safety issues. Lipid nanoparticle (LNP) technology, as an advanced gene delivery platform, offers significant advancements to CAR-T therapy through its high efficiency, low immunogenicity, and safety. LNP enablein vivoproduction of CAR-T cells, thereby improving delivery efficiency, reducing the risks of immunogenicity and insertional mutations, simplifying the production process and reducing costs. The scalability and rapid optimization ability of LNP position them as promising candidates for CAR-T cell production. LNP technology is expected to further promote the development of CAR-T immunotherapy and provide safer and more economical treatment options. Therefore, this paper aims to provide a comprehensive and systematic review of the application of LNP in CAR-T therapy. In this review, we initially outline the fundamental design, process, and current challenges of CAR-T therapy. Subsequently, we present the characteristics of LNP, their advantages as a gene delivery vectors, and how they improve the efficacy of CAR-T therapy. Finally, we summarize the current research landscape of LNP applications in CAR-T therapy. This includes enhancingin vitrotransfection of T cells, programming T cellsin situ, facilitating T-cell activation, alleviating the side effects of CAR-T therapy, and combining CAR-T therapy with other immunotherapies. These advancements will aid in the design of mRNA delivery systems based on LNP, thereby promoting the development of CAR-T therapy.