Converting localized tumor destruction into systemic antitumor immunity remains a central challenge in cancer immunotherapy. In this study, we present a rationally designed antigen-capturing nanoplatform composed of tannic acid (TA) and saponin, which self-assemble to encapsulate photosensitizer, forming saponin-polyphenol nanoparticles (ISNPs) with multifunctional immunotherapeutic potential. Leveraging the membrane-perturbing properties of saponin, ISNPs induce acute plasma membrane disruption and promote the release of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT) and high-mobility group box 1 (HMGB1), thereby initiating immunogenic cell death (ICD) and supporting subsequent immune activation. Simultaneously, ISNPs induce nuclear membrane rupture and cytosolic DNA leakage. Notably, the polyphenol-rich surface of ISNPs enables efficient adsorption of tumor-associated antigens (TAAs), forming antigen–nanocomplexes that prolong antigen retention and facilitate dendritic cell (DC) uptake. In bilateral tumor-bearing mouse models, ISNP-mediated photothermal treatment not only eradicates primary tumors but also elicits a modest abscopal trend on distant lesions, marked by enhanced DC maturation and cytotoxic T lymphocyte infiltration. This work establishes a membrane-interfering, antigen-capturing nanoagent that effectively bridges local photothermal ablation and systemic immune activation, offering a promising strategy for in situ nanovaccination and personalized cancer immunotherapy.

In situ vaccines have shown promise in cancer treatment but encounter obstacles such as limited tumor antigen release, immune-suppressive microenvironments, and insufficient antigen processing. To boost the effectiveness of in situ cancer vaccine, the rationally designed delivery technologies are urgently needed for improved immunotherapy. In the current study, NanoAlum based delivery system has been developed which could function for all the courses during the in situ vaccine formation, including immunogenic cancer death (ICD) induction, immunomodulator (R848) loading as well as carriers for autologous antigens. After intratumoral administration, the NanoAlum based delivery system would induce ICD upon near-infrared (NIR) heating for tumor-derived antigens release. The antigens would then be captured by NanoAlum therefore in situ cancer nanovaccine could be formed with the three moieties: autologous antigens by ICD, R848 as immunoadjuvant, and NanoAlum as delivery system. Under this paradigm, the NanoAlum based delivery system would optimize the efficacy of cancer vaccines by enhancing antigenicity, adjuvanticity, and modulation of immune suppression within the tumor microenvironment, thereby initiating a multistep cascade of antitumor responses. In vivo experiments demonstrated that NanoAlum based delivery system would generate complete eradication of primary tumors, potent abscopal effects on distant tumors and long-term immune response against cancer recurrence. More importantly, the safety of all the compositions within the vaccine has been proved by clinical trials, which makes it highly attractive for clinical translation. Overall, the attempt demonstrates the great potential of in situ cancer vaccine based on NanoAlum delivery system in boosting immunotherapy for cancer treatment.

Nanoparticles induced potent antitumor immunotherapy plays a significant role for enhancing conventional therapeutic effectiveness. However, revealing the pathway of how nanoagents themselves trigger the host immunity or how to maximize the immunotherapy efficacy still needs further exploration. Herein, rose-like MoS₂ nanoflowers modified with 2-deoxy-D-glucose (2-DG) and glucose oxidase (GOx) (MPGGFs) have been successfully fabricated via a one-pot hydrothermal reaction and following one-by-one surface modification as a multifunctional nanocatalyst for photothermal therapy enhanced self-amplified chemodynamic immunotherapy (PTT-co-CDT). By introducing GOx, the obtained MPGGFs exhibited self-amplified chemodynamic therapeutic efficacy under hypoxia tumor microenvironment (TME) because of the raised intracellular H₂O₂ level via enzyme-catalysis of oxygen. Furthermore, combined with the intrinsic excellent photothermal conversion efficiency of MoS₂ nanoflowers, PTT-co-CDT performances by MPGGFs could effectively induce the necroptosis of tumor cells both in vitro and in vivo. Then the induced necroptosis via PTT-co-CDT by MPGGFs could directly trigger host immunity by activating the antigen-specific T-cells (CD4⁺ and CD8⁺). Finally, the excellent in vivo safety of MPGGFs makes us believe that the successful construction of rose-like multifunctional nanocatalyst not only has great potentials for self-amplified chemodynamic immunotherapy, but also provides a paradigm for exploring necroptosis triggered host immunity for cancer treatment.

Molybdenum disulfide (MoS₂), a typical transition-metal dichalcogenide, has attracted increasing attention in the field of nanomedicine because of its preeminent properties. In this study, magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of human breast cancer xenograft in nude mice was demonstrated using a novel core/shell structure of Fe₃O₄@MoS₂ nanocubes (IOMS NCs) via the integration of MoS₂ (MS) film onto iron oxide (IO) nanocubes through a facile hydrothermal method. After the necessary PEGylation modification of the NCs for long-circulation purposes, such PEGylated NCs were further capped by 2-deoxy-D-glucose (2-DG), a non-metabolizable glucose analogue to increase the accumulation of the as-prepared NCs at the tumor site, as 2-DG molecules could be particularly attractive to resource-hungry cancer cells. Such 2-DG-modified PEGylated NCs (IOMS-PEG-2DG NCs) acted as drug-carriers for doxorubicin (DOX), which could be easily loaded within the NCs. The obtained IOMS-PEG(DOX)-2DG NCs exhibited a T₂ relaxivity coefficient of 48.86 (mM)^-1·s^-1 and excellent photothermal performance. 24 h after intravenous injection of IOMS-PEG(DOX)-2DG NCs, the tumor site was clearly detected by enhanced T₂-weighted MRI signal. Upon exposure to an NIR 808-nm laser for 5 min at a low power density of 0.5 W·cm^-2, a marked temperature increase was noticed within the tumor site, and the tumor growth was efficiently inhibited by the chemo-photothermal effect. Therefore, our study highlights an excellent theranostic platform with great potential for targeted MRI-guided precise chemo-photothermal therapy of breast cancer.