Nanovaccines of polydopamine@tumor-associated antigens with robust prophylactic and therapeutic efficacy for cancer immunotherapy

Abstract

One of the most common strategies used in cancer immunotherapy is the development of vaccines based on tumor-associated antigens (TAAs). However, the limitations of low antigen loading efficiency and insufficient tumor targeting ability result in suboptimal therapeutic outcomes. Polydopamine (PDA) can conjugate with multiple functional molecules or moieties through covalent coupling reactions and serve as a crucial bridging component in the construction of nanovectors. In this study, we developed a nanovaccine (PDAT) by conjugating PDA with 4T1 tumor-associated antigens (4T1-Ag). PDAT possesses potent immunostimulatory ability, which could efficaciously activate powerful tumor-specific humoral and cellular responses to achieve high prophylactic and therapeutic efficacy in both in situ and distal tumor models, as well as in prophylactic murine models. This study provides a straightforward yet efficient strategy for fabricating nanovaccines with high antigen-loading capacity for tumor immunotherapy.

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New concepts

This work demonstrates a new concept of constructing a high-efficiency nanovaccine platform via covalent conjugation of polydopamine (PDA) with immunogenic cell death (ICD)-derived whole tumor antigens, achieving significantly enhanced antigen loading (72.5%) and improved antigen delivery and presentation. Unlike conventional nanovaccines that often suffer from low loading efficiency, weak antigen–carrier interactions, and complex functionalization, this PDA-based strategy leverages inherent adhesion and biocompatibility to form stable antigen complexes without additional targeting moieties. This study provides fundamental insight into how nanoscale adhesion chemistry can be harnessed to promote dendritic cell maturation, amplify tumor-specific immune responses, and remodel the immunosuppressive microenvironment, offering a simple yet versatile nanosystem for both prophylactic and therapeutic cancer immunotherapy.

1. Introduction

Unlike traditional therapies such as chemotherapy and radiotherapy, immunotherapy recognizes and eliminates tumor cells by mobilizing host immunity,^1,2 which has tremendous potential in clinical antitumor therapy, due to its good therapeutic outcomes and few side effects. Cancer immunotherapy is mainly divided into five categories: (1) molecular targeted therapy,^3–7 (2) immune checkpoint blockade therapy (ICB),^8–11 (3) chimeric antigen receptor therapy (CAR-T),¹² (4) cytokine therapy,¹³ and (5) tumor vaccines.^14–17 Among these, tumor vaccines can provoke antitumor immune responses by delivering antigens to antigen-presenting cells (APCs), and hold significant potential for the prevention and management of cancer. Consequently, it is of great significance to develop efficient delivery vehicles for tumor vaccines.

Nowadays, various vectors¹⁸ have been utilized to construct cancer nanovaccines,^19–24 such as carbon dots,^25–27 inorganic nanoparticles,^28–32 organometallic frameworks^33–35 and hydrogels.³⁶ Our group has been actively engaged in the development of nanovaccines. We synthesized a chiral nanovaccine (L/D-OVA) using chiral CDs and ovalbumin (OVA). Dendritic cells (DCs) were able to efficiently absorb L/D-OVA, which encouraged DC maturation and stopped the proliferation of B16-OVA melanoma.³⁷ In addition, we constructed nanovaccines by conjugating CDs with antigens derived from tumor cells. These nanovaccines efficiently promoted the cross-presentation of antigens, specifically targeted B16F10 or CT26 cancer cells, and considerably inhibited tumor growth.³⁸ However, some drawbacks need to be addressed, including complex preparation processes, low loading efficiency, and insufficient stability. Besides, the weak interactions between nanovectors and antigens may cause suboptimal antigen absorption and presentation. To obviate these shortcomings, developing an efficient and versatile carrier to enhance the delivery and presentation of antigens is of great significance.

Polydopamine (PDA)^39–41 is a biomimetic polymer with good biocompatibility⁴² and low toxicity^43,44 that can be prepared by self-polymerization of dopamine. Due to its excellent photothermal performance,^45–47 as well as high adhesion,^48–50 PDA is commonly employed in bioelectrochemical sensing,^51,52 drug delivery,^53–55 and cancer treatment.⁵⁶ PDA has a lot of amine, quinone, and α,β-unsaturated ketone groups, which make them great anchors for amidation, Michael addition, or Schiff base reactions to connect with other functional molecules. In addition, PDA can play an immunomodulatory role in a variety of immune cells through dopamine receptors and related proteins.⁵⁷

However, PDA-based systems still face several critical limitations in cancer immunotherapy: suboptimal antigen-loading efficiency – although PDA can effectively bind tumor-associated antigens, its loading capacity is generally inferior to that of lipid- or polymer-based carriers (e.g., liposomes or PLGA nanoparticles), restricting its applicability in high-dose vaccine formulations; the lack of intrinsic tumor-targeting ability. PDA itself does not possess inherent tumor-homing properties, necessitating the incorporation of additional targeting moieties (e.g., peptides and antibodies) to achieve precise delivery. This requirement complicates the rational design and manufacturing of PDA-based nanovaccines; the risk of off-target immune activation. Due to its inherent immunogenicity, PDA may provoke nonspecific immune stimulation, potentially leading to systemic inflammatory responses or autoimmune-like adverse effects; and uncontrolled polymerization kinetics and batch-to-batch variability. The synthesis of PDA nanoparticles is highly dependent on reaction conditions (e.g., pH and oxygen concentration), often resulting in inter-batch inconsistencies in particle size, morphology, and functionality.

Considering the properties of PDA, we constructed a PDA/TAA nanovaccine (PDAT) by conjugating PDA with TAAs obtained via chemotherapy-induced immunogenic cell death (ICD) (Scheme 1). The PDAT nanovaccine exhibited excellent colloidal stability and homogeneous dispersion, while demonstrating significantly enhanced antigen-loading efficiency (72.5%) compared to conventional formulations reported in previous studies. PDAT can improve antigen presentation, stimulate DC maturation, and activate T cells. As a proof of concept, we established primary and distal tumor models to demonstrate that PDAT could trigger a powerful systemic immune response by encouraging the infiltration of immune cells in the tumor location, upgrading levels of pro-inflammatory factors (TNF-α, IFN-γ, and IL-6) and downregulating the expression of MDSCs and Tregs. Ultimately, the treatment demonstrated significant efficacy in inhibiting tumor progression and even in inducing tumor regression, while maintaining an excellent safety profile without observable adverse effects in murine models. Furthermore, we evaluated the cancer preventive effect of PDAT on prophylactic murine models and the results proved that PDAT could potently induce humoral and cellular immune responses, relieve the immunosuppressive tumor microenvironment, delay tumor growth and prevent tumorigenesis.

Scheme 1 Schematic representation of the immunological reaction in vivo induced by PDAT.

2. Experimental

2.1. Synthesis of PDA

A Tris–HCl solution (10 mM, pH 8.8, 2 mL) of dopamine (DA, 1 mg mL⁻¹) was stirred at room temperature for 0.5 h. The solution gradually changed from colorless to black. Finally, the solution was centrifuged and washed twice with water.

2.2. Synthesis of 4T1-Ag

Tumor cells (4T1) were inoculated into culture dishes and incubated overnight. Taxol (30 µM) was added to the dishes and incubated for 48 h. The cell culture supernatant was then collected and centrifuged at 2000 rpm in an ultrafiltration tube for 5 min to remove dead cells and cell debris, and the supernatant was washed once with PBS to obtain the tumor antigen. The DNA percentage in 4T1-Ag was 0.084%.

2.3. Synthesis of PDAT

1 mL of 4T1 tumor antigen (4T1-Ag) was added to 2 mL of PDA solution and stirred at room temperature for 1 h. The solution was then collected and centrifuged in an ultrafiltration tube at 2000 rpm for 5 min to remove free tumor antigens, and the supernatant was washed once with Tris–HCl to obtain PDAT.

3. Results and discussion

3.1. Characterization of PDAT

PDA was prepared by stirring DA at room temperature for 0.5 h. The transmission electron microscopy (TEM) image (Fig. 1a) illustrates that PDA was ellipsoidal in morphology with a size of approximately 34.6 nm. Radiotherapy, phototherapy, and chemotherapy can induce immunogenic cell death in tumor cells.^58–61 Therefore, we used Taxol to mediate the ICD of 4T1 tumor cells, so as to prepare TAAs. As demonstrated in Fig. S1, as soon as the Taxol concentration reached 30 µM, almost all 4T1 cells died. After Taxol caused tumor cells to undergo apoptosis, the released tumor antigens were collected and named 4T1-Ag. We detected calreticulin (CRT) and high mobility group box 1 protein (HMGB1) of 4T1 cells using an Operetta CLSTM High Content Analysis System. Taxol caused an enormous quantity of CRT to be exposed on the cell surface and HMGB1 to be released (Fig. S2), further demonstrating that Taxol successfully induced ICD in tumor cells. The prepared 4T1-Ag was mixed with PDA and agitated. After ultrafiltration, PDAT was obtained. As shown in Fig. 1b, PDAT was ellipsoidal and well dispersed with a size of 100.2 nm. The UV-vis absorption spectrum of PDAT (Fig. 1c) has two peaks at 216 and 282 nm, which is consistent with that of PDA, confirming the successful synthesis of PDAT. The zeta potentials of PDA, 4T1-Ag and PDAT were −43.8, −10.2 and −39.0 mV, respectively (Fig. 1d). The hydrodynamic diameters (HD) of PDA and PDAT were 190.1 and 295.3 nm, respectively, as determined by DLS (Fig. S3 and Fig. 1e). Fig. S4 shows the stability of PDA and PDAT in different solutions, indicating that PDA and PDAT are stable under physiological conditions. SDS-PAGE analysis (Fig. 1f) showed that the band corresponding to 4T1-Ag appeared in PDAT, further demonstrating that PDAT was successfully prepared.

Fig. 1 Characterization of PDAT. TEM images of (a) PDA and (b) PDAT. (c) UV-vis absorption spectra of PDA and PDAT. (d) Zeta potentials of PDA, 4T1-Ag and PDAT. (e) HD of PDAT. (f) SDS-PAGE analysis of PDA, 4T1-Ag and PDAT.

3.2. PDAT promotes DC maturation

The antigen content in PDAT determined using a BCA protein assay kit (Fig. S5) was 57.1%. The loading efficiency (EE, %) of the antigen was 72.5%. The MTT assay illustrated that the cell survival rate remained above 80% after treatment with PDA. Meanwhile, the cell viability of the 4T1-Ag and PDAT treatments reached approximately 100% (Fig. 2a), indicating that PDAT was non-toxic to DC2.4 cells. We further investigated the ability of PDA, 4T1-Ag and PDAT to enter DC2.4 cells. PDA, 4T1-Ag and PDAT were labeled with FITC and then incubated with DC2.4 cells. The CLS™ high content images (Fig. 2b) depict a more intense green fluorescence in the PDATFITC compared to the other two treatments, indicating that PDAT could be efficiently internalized by DC2.4 cells. When the vaccine enters the organism, it is recognized by DCs. Then, DCs display the antigen on the MHC-II site on their surface. The TCR recognizes the antigen presented by the MHC molecule and transmits this signal from the surface of the T cell into the cell (Fig. 2c). We therefore investigated the expression of MHC-II. DC2.4 cells treated with PBS, PDA, 4T1-Ag, PDAT and LPS, respectively, for 12 h. As shown in Fig. 2d and Fig. S6, the expression of MHC-II was 5.02%, 6.19% and 9.47% for PBS, PDA and 4T1-Ag treatments, respectively. After PDAT treatment, the percentage of MHC-II on the surface of DC2.4 cells reached 18.2%. A hallmark of DC maturation is the upregulation of CD80 and CD86 expression. As shown in Fig. 2e and Fig. S7, when DC2.4 cells were stimulated with PBS, PDA and 4T1-Ag, their expression of CD80⁺ CD86⁺ was only 16.2%, 16.9% and 25.3%, whereas PDAT could significantly stimulate DC maturation, with a CD80⁺ CD86⁺ DC% of 33.8%. We quantified the concentrations of several proinflammatory factors, including TNF-α, IFN-γ and IL-6. By standard curves (Fig. S8–S10), the concentrations of TNF-α, IFN-γ and IL-6 in the PDAT group were 35.15, 39.47 and 54.14 pg mL⁻¹, respectively (Fig. 2f–h). These results indicate that PDAT could stimulate DC2.4 maturation and enhance cytokine secretion.

Fig. 2 PDAT could stimulate DC maturation. (a) Cell viability of DC2.4 cells after treatment with PDA, 4T1-Ag and PDAT. (b) CLS™ high content images of DC2.4 cells treated with PDA, 4T1-Ag and PDAT. (c) Schematic representation of antigen presentation by DCs. (d) Expression of MHC-II and (e) CD80⁺ CD86⁺ expression in DC2.4 cells after incubation with different treatments. Expression levels of TNF-α, IFN-γ and IL-6 in DC2.4 cells. Data are expressed as mean ± SD (significance analysis was performed using a two-tailed t-test. ns: not significant, *p < 0.05, **p < 0.01, and ***p < 0.001, n = 4).

To further substantiate the above findings, we performed immunofluorescence (IF) experiments. DC2.4 cells incubated with PBS, PDA and 4T1-Ag emitted weak green fluorescence (Fig. 3a). By contrast, the cells treated with PDAT presented strong fluorescence. PDAT stimulated the maturation of DC2.4 cells, thereby significantly upregulating CD80 expression. Similarly, PDAT also upregulated the level of CD86 (Fig. 3b). Another feature of DC maturation is generating many dendritic arbors. Therefore, the DC cytoskeletons were stained using G-actin and observed using a CLS^TM high content imaging system. The fluorescence intensity in the PBS, PDA and 4T1-Ag groups was weak and there was no obvious change in the cell morphology (Fig. 3c). However, after stimulation with PDAT, the morphology of DC2.4 cells markedly changed, along with the appearance of many dendritic structures, further confirming that PDAT could significantly stimulate the maturation of DCs.

Fig. 3 IF analysis of (a) CD80 and (b) CD86 expressed by DC2.4 cells, after incubation with PBS, PDA, 4T1-Ag, PDAT and LPS. (c) Fluorescence images of DC cytoskeletons (blue: DAPI; green: cytoskeleton).

3.3. PDAT inhibits tumor growth

B16-OVA cells were injected into the back of the mice to establish a hormonal mouse model (D 15) to verify the antigen specificity of PDAT (Fig. S11a). After 8 days, the tumor started to grow. When the tumor volume attained 80 mm³ (D 1), mice were given subcutaneous injections of PBS, PDA, 4T1-Ag, or PDAT every 5 days for a total of 5 times. The dose was 5 mg kg⁻¹ of nanovaccine per mouse. The mice gradually gained weight throughout the immunization period, indicating that PDAT had no obvious toxic side effects (Fig. S11b). Since PDAT was prepared from 4T1 tumor cell lysates, it could not inhibit B16-OVA tumors. Thus, the tumor growth was not inhibited in the 4T1-Ag and PDAT groups (Fig. S11c–e). This result suggests that PDAT is antigen-specific and cannot generate an immune response to other antigens.

Therewith, we established primary and distant 4T1 tumor models on the right and left sides of the mice (Fig. 4a). On day 1, PBS, PDA, 4T1-Ag or PDAT was injected subcutaneously into the mice and then administered every five days. In the course of the therapy, body weight increased and hematological analysis revealed all physiological parameters within normal ranges (Fig. S12), indicating that PDAT had a relatively high safety profile at this dose (Fig. 4b). Fig. 4c displays growth curves of the primary tumor. In comparison to the rapid tumor growth of the PBS, PDA and 4T1-Ag groups, PDAT strikingly suppressed the tumor progression. Likewise, the growth of distal tumors on PDAT treatment (Fig. 4d) was remarkably restrained, with one complete regression of a tumor. PDAT treatment yielded inhibition rates of 84.96% for primary tumors (Fig. S13a) and 83.73% for distant tumors (Fig. S13b). In addition, among the four groups, not only the primary tumors but also the distal tumors in the PDAT group had the lowest weight (Fig. 4e and f), which was also confirmed by tumor photographs (Fig. 4g and h). H&E staining analysis showed that the nuclei of tumor tissues in the PBS, PDA and 4T1-Ag treatments were dense, while the nuclei in the PDAT group were lysed. The major organs had no pathological changes (Fig. S14). These results indicated that PDAT had a significant therapeutic benefit on both primary and distal tumors with a high safety profile.

Fig. 4 Therapeutic efficacy of PDAT for 4T1 tumors. (a) Treatment schedule for 4T1 tumors in BalB/c mice. (b) Average weight growth curve of mice. Curves of (c) primary and (d) distal tumor growth over time. The mean tumor weight of (e) primary and (f) distal tumors. Pictures of (g) primary and (h) distal tumors. Data are expressed as mean ± SD (significance analysis was performed using a two-tailed t-test. ns: not significant, *p < 0.05, **p < 0.01, and ***p < 0.001, n = 5).

3.4. PDAT induces immune responses in mice

We then analyzed various immune parameters of the mice. Fig. 5a and b reveal the maturation of DCs in the inguinal LNs of mice. It was observed that PBS, PDA and 4T1-Ag induced only 2.96%, 3.62% and 5.04% DC maturation, whereas the maturation of DC in the PDAT group reached 11%. In addition, PDAT significantly activated T cells in LNs with positive percentages of 19.7% for CD3⁺ CD4⁺ T cells (Fig. S15a and b) and 15.4% for CD3⁺ CD8⁺ T cells. (Fig. 5c and d). Similarly, PDAT stimulated the DC maturation (Fig. S16) and activation of CD3⁺ CD4⁺ T cells (Fig. S17a and b) and CD3⁺ CD8⁺ T cells in spleens (Fig. S17c and d). The therapeutic effect is influenced by immune cell infiltration within the tumor. Thus, we estimated the proportion of CD80⁺ CD86⁺ DCs in the tumor. After PDAT treatment, CD80⁺ CD86⁺ DC was significantly upregulated to 6.69% (Fig. S18). Similarly, the expression of CD3⁺ CD4⁺ T cells and CD3⁺ CD8⁺ T cells in the PDAT was much higher than that in other groups, with the percentages of 7.65% (Fig. S19a and b) and 10.5%, respectively (Fig. S19c and d). MDSCs and Tregs are the major contributors to the immunosuppressive tumor microenvironment, and can downregulate the immune response and favour tumor progression. As depicted in Fig. 5e and f, the percentage of MDSCs in the PBS, PDA and 4T1-Ag groups was 20.1%, 16.8% and 13.9%, respectively. By contrast, the MDSC content in the PDAT group was reduced to 8.22%. Similarly, the percentage of Tregs in tumor tissues was reduced to 6.48% after PDAT treatment (Fig. 5g and 5h). Next, we examined the concentration of pro-inflammatory factors in the serum. The serum levels of TNF-α in the PBS, PDA, 4T1-Ag and PDAT treatments were 23.67, 31.54, 39.6 and 61.21 pg mL⁻¹, respectively (Fig. 5i). Moreover, the IFN-γ and IL-6 levels in the PDAT group were 24.34 pg mL⁻¹ and 50.2 pg mL⁻¹, respectively (Fig. 5j and k), which was far greater than other groups. According to the aforementioned findings, PDAT can not only upregulate the immune response in vivo, but also alleviate the tumor immunosuppressive microenvironment, downregulate the expression of MDSCs and Tregs, and further enhance the therapeutic efficiency.

Fig. 5 PDAT triggered the immune response in mice. (a) and (b) Maturation of DCs in LNs. Percentage of (c) and (d) CD3⁺ CD8⁺ T cells in LNs. (e) and (f) Percentage of MDSCs in tumors. (g) and (h) Percentage of Tregs in tumors. The serum concentration of (i) TNF-α, (j) IFN-γ and (k) IL-6 in mice. Data are expressed as mean ± SD (significance analysis was performed using a two-tailed t-test. ns: not significant, *p < 0.05, **p < 0.01, and ***p < 0.001, n = 5).

To reconfirm that PDAT could improve the tumor microenvironment, we performed immunofluorescence section analysis of the tumor tissues. The red fluorescence in the PDAT treatment was much stronger than that of the PBS, PDA and 4T1-Ag groups (Fig. S20a and b), indicating that the tumor tissue in the PDAT group expressed the most CD4⁺ and CD8⁺ T cells. Since PDAT could alleviate the tumor immune microenvironment, the amount of Tregs in the PDAT group was also significantly down-regulated (Fig. S20c). These findings confirm that PDAT can stimulate T cell activation and alleviate the immunosuppressive tumor microenvironment.

3.5. PDAT prevents the growth of 4T1 tumors

Inspired by the favorable therapeutic effect of PDAT, we established a 4T1 prophylactic murine model to further validate its prophylactic capability against cancers. First, BalB/c mice were immunized by the subcutaneous injection of PBS, PDA 4T1-Ag or PDAT every five days. The mice were challenged with 4T1 tumor cells three days following their most recent inoculation, and the tumor development was subsequently tracked (Fig. 6a). There was no weight loss in the mice throughout the immunization process, demonstrating the acceptable safety profile of PDAT (Fig. 6b). Intriguingly, after PDAT immunization, the tumor growth was significantly inhibited (Fig. 6c); especially, two tumors were completely prevented (Fig. 6d). The average tumor weight in the PBS, PDA, 4T1-Ag and PDAT was 1.26, 1.08, 0.92 and 0.06 g, respectively (Fig. 6e), confirming the excellent tumor-preventive efficacy of PDAT. H&E staining demonstrated that PDAT significantly killed tumor cells and had a reliable safety profile (Fig. S21).

Fig. 6 The preventive effect of PDAT for 4T1 tumors. (a) Experimental schedule for prophylactic cancer challenges. (b) Curve of the body weight of mice over time. The (c) growth curve and (d) picture of the tumor. (e) Tumor weight in each group. Data are expressed as mean ± SD (significance analysis was performed using a two-tailed t-test. ns: not significant, *p < 0.05, **p < 0.01, and ***p < 0.001, n = 5).

3.6. PDAT triggers immune memory in mice

To further understand the in vivo immune mechanism of antigen-specific tumor prevention induced by PDAT, we analyzed the relevant immune cells in the LNs, spleens and tumors. PDAT significantly stimulated the maturation of DCs in the LNs (Fig. 7a and b) and induced the activation of approximately 25.6% of CD3⁺ CD4⁺ T cells (Fig. 7c and d) and 20.5% of CD3⁺ CD8⁺ T cells (Fig. 7e and f). The spleens contained 12.9% of mature DCs (Fig. S22), 11.2% of CD3⁺ CD4⁺ T cells, and 7.56% of CD3⁺ CD8⁺ T cells (Fig. S23). To verify whether PDAT induced immune memory in mice, we analyzed the expression of effector memory T cells (Tems) in the spleens. As shown in Fig. 7g and h, the percentage of Tems in the PBS, PDA and 4T1-Ag groups was 6.77%, 14.8 and 17.6%, respectively. In comparison, PDAT elicited the strongest immune memory with a percentage of Tems of 23%, which was conducive to protecting the mice from the attack of tumor cells. PDAT stimulated DC maturation, with 15.7% of CD80⁺ CD86⁺ DCs (Fig. S24), and the proportion of CD3⁺ CD4⁺ T cells (19.5%) and CD3⁺ CD8+ T cells (27.2%) was also significantly upregulated compared to the other groups (Fig. S25). In addition, PDAT also improved the tumor microenvironment by downregulating the levels of MDSCs and Tregs by 10.9% and 7.38% (Fig. S26), respectively. Fig. 7i–k shows the levels of cytokines in the mouse serum, respectively, and PDAT significantly upregulated the concentrations of TNF-α, IFN-γ, and IL-6, which were 9.35, 10.38, and 0.73 pg mL⁻¹, respectively.

Fig. 7 PDAT could trigger immune responses and immune memory in mice. (a) and (b) Maturation of DCs in the LNs. Percentage of CD3⁺ CD4⁺ T cells (c) and (d) and CD3⁺ CD8⁺ T cells (e) and (f) in the LNs. (g) and (h) Expression of Tems in the spleens. (i)–(k) The concentration of pro-inflammatory factors in the serum. Data are expressed as mean ± SD (significance analysis was performed using a two-tailed t-test. ns: not significant, *p < 0.05, **p < 0.01, and ***p < 0.001, n = 5).

4. Conclusions

PDA was effectively conjugated with tumor antigens (4T1-Ag) to prepare a nanovaccine (PDAT). PDAT possesses excellent biocompatibility and outstanding antigen delivery and presentation capabilities, which facilitate DC maturation, activate multiple effector T cells, and simultaneously enhance the secretion of cytokines. After subcutaneous immunization, PDAT enhanced CD4⁺ and CD8⁺ T cell intratumoral infiltration and relieved the tumor immunosuppressive microenvironment, thereby inducing enduring antitumor immunity in the therapeutic 4T1 primary and distal tumor models. Moreover, PDAT demonstrated durable protective antitumor immunity in the prophylactic murine model, which significantly postponed tumor growth and even restrained oncogenesis. This work highlights a straightforward yet flexible platform for antigen delivery and presentation, which provides a simple but universal platform for cancer immunotherapy.

Author contributions

Hongxin Liu: methodology, investigation, software, and writing – original draft; Min Zheng: conceptualization, resources, supervision, writing – review and editing, and data curation; Zhigang Xie: conceptualization, resources, supervision, and writing – review and editing.

Conflicts of interest

There are no conflicts to declare.

Data availability

Supplementary information (SI) is available. See DOI: https://doi.org/10.1039/d5nh00681c.

Acknowledgements

This study was financially supported by the Jilin Province Science and Technology Research Project (YDZJ202601ZYTS549).

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