Bioinspired Nanocomplexes Comprising Phenolic Acid Derivative and Human Serum Albumin for Cancer Therapy.

Inspired by the natural phenomenon of phenolic-protein interactions, we translate this "naturally evolved interaction" to a "phenolic acid derivative based albumin bound" technology, through the synthesis of phenolic acid derivatives comprising a therapeutic cargo linked to a phenolic motif. Phenolic acid derivatives can bind to albumin and form nanocomplexes after microfluidic mixing. This strategy has been successfully applied to different types of anticancer drugs, including taxanes, anthraquinones, etoposides, and terpenoids. Paclitaxel was selected as a model drug for an in-depth study. Three novel paclitaxel-phenolic acid conjugates have been synthesized. Molecular dynamics simulations provide insights into the self-assembled mechanisms of phenolic-protein nanocomplexes. The nanocomplexes show improved pharmacokinetics, elevated tolerability, decreased neurotoxicity, and enhanced anticancer efficacies in multiple murine xenograft models of breast cancer, in comparison with two clinically approved formulations, Taxol (polyoxyethylated castor oil-formulated paclitaxel) and Abraxane (nab-paclitaxel). Such a robust system provides a broadly applicable platform for the development of albumin-based nanomedicines and has great potential for clinical translation.

Liposomal Nanodrug Based on Norcantharidin Derivative for Increased in Vivo Activity.

To address the limitations of norcantharidin (NCTD) in clinical applications, including restricted tumor accumulation and intense irritation, we have developed a new derivative of NCTD with (S)-1-benzyl-3-pyrrolidinol, which can be actively loaded into liposomes to achieve drug encapsulation and sustained release properties by using pH gradient loading technique. Cytotoxicity tests against cancer cell lines (Hepa 1-6 and 4 T1 cells) have demonstrated that this derivative exhibits comparable activity to NCTD in vitro. The NCTD derivative can be efficiently loaded into liposomes with high encapsulation efficiency (98.7%) and high drug loading (32.86%). Tolerability and antitumor efficacy studies showed that the liposomal NCTD derivative was well tolerated at intravenous injection doses of 3 folds higher than the parent drug solution, while significantly improved anticancer activity in vivo was achieved. This liposomal nanodrug could become a potent and safe NCTD formulation alternative for cancer therapy.

The association between circulating neutrophil extracellular trap related biomarkers and retinal vein occlusion incidence: A case-control pilot study.

Retinal vein occlusion (RVO) is the second most common retinal vascular disorders and causes visual damage in a large population. Neutrophil extracellular traps (NETs) formation (NETosis) is an important cause of vascular diseases, however, the association between NETs related biomarkers and RVO development remained unclear. In this pilot study, a total of 77 RVO cases and 48 controls were included between Jan 2020 and July 2020. Besides, the circulating levels of three NETs related markers, cell-free DNA (cfDNA), myeloperoxidase (MPO)-DNA and citrullinated histone H3 (H3Cit), were detected in all the participants and thus the association between NETosis and RVO incidence was analyzed. Advanced assays were conducted to investigate the inflammation and thrombosis related biomarkers in RVO cases with higher or lower NETs biomarkers. When the results were considered, it was found that NETs biomarkers, including cfDNA, MPO-DNA and H3Cit, were increased in the RVO cases comparing with the controls (P < 0.05). Through the receiver operating characteristic (ROC) analyses, we found that circulating NETs related biomarkers demonstrated potential diagnostic effects for RVO and the AUCs of plasma cfDNA, MPO-DNA and H3Cit were 0.859, 0.871 and 0.928, respectively (P < 0.001). Through analyzing the correlations between circulating NETs markers and RVO stages and durations, inflammatory markers as well as thrombotic indexes, it was found that NETs were related with the RVO subtypes, inflammatory status and thrombus formation. In conclusion, the plasma NETs remnants are significantly increased in RVO cases. Besides, advanced studies demonstrate that inflammation as well as thrombus formation might be involved in this association.

Preparation of ursolic acid-phospholipid complex by solvent-assisted grinding method to improve dissolution and oral bioavailability.

To improve the aqueous solubility and the oral bioavailability of a poorly water-soluble biologically active pentacyclic triterpenoid, ursolic acid (UA), ursolic acid-phospholipid complex (UA-PC) was prepared using solvent-assisted grinding method which is green and simple. The phospholipid complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscope (SEM), and transmission electron microscope (TEM), which confirmed the formation of the phospholipid complex. Specifically, compared with free UA, the formulation demonstrated over 276-fold higher aqueous solubility of UA and exhibited faster dissolution rate and higher cumulative dissolution percentages. Finally, the oral bioavailability of the prepared UA-PC was evaluated using Sprague-Dawley (SD) rats. Compared with free UA, the UA-PC exhibited considerable enhancement in the bioavailability with an increase in Cmax (183.80 vs 68.26 µg/l) and AUC 0-24 h (878.0 vs 212.1 µg·h/l), which was consistent with the in vitro results. This enhancement was attributed to the improvement of solubility and dissolution in vitro. Therefore, the method of solvent-assisted grinding appears to be an efficient approach for the preparation of UA-PC, and the prepared UA-PC showed a promising potential to overcome the limitation of poor oral bioavailability associated with low water solubility.

A sensitive, high-throughput, and ecofriendly method for the determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin by supercritical fluid chromatography and tandem mass spectrometry.

A quick and sensitive supercritical fluid chromatography with tandem mass spectrometry method for the simultaneous determination of lumefantrine, artemether, and its active metabolite dihydroartemisinin in rat plasma was developed and validated. The chromatographic separation was performed on an ACQUITY UPC2 ™ BEH 2-EP column within 2.5 min by gradient elution using compressed CO2 and methanol containing 2 mM ammonium acetate as the mobile phases. Detection was achieved by multiple reaction monitoring using electrospray ionization in the positive ionization mode. For sample preparation, 50 µL of the sample was processed by modified high-throughput, one-step protein precipitation using hydrogen peroxide as a stabilizer to protect the endoperoxide-containing artemisinin derivatives from degradation. The calibration curves were linear over the concentration range of 2.0-1000 ng/mL for both artemether and dihydroartemisinin, and 1.0-5000 ng/mL for lumefantrine. The values of selectivity, lower limit of quantification, linearity, accuracy, precision, matrix effects, stability, and recovery met the acceptable range according to the Food and Drug Administration guidelines. The developed method enables high resolution and speed as well as low cost, low solvent consumption, and short time and was successfully applied to pharmacokinetic studies through the intravenous administration of an artemether-lumefantrine lipid emulsion in rats.

A mitochondrial targeting tetrapeptide Bendavia protects lateral line hair cells from gentamicin exposure.

The hearing loss induced by aminoglycosides is caused by the permanent loss of mechanosensory hair cells of the inner ear. The aim of the present study is therefore to evaluate the protective effect of Bendavia, a novel antioxidant, on gentamicin-induced hair cell damage in zebrafish lateral lines. The results demonstrated the pretreatment of Bendavia exhibited dose-dependent protection against gentamicin in both acute and chronic exposure. We found that Bendavia at 150 µm conferred optimal protection from either acute or chronic exposure with ototoxin. Bendavia reduced uptake of fluorescent-tagged gentamicin via mechanoelectrical transduction channels, suggesting its protective effects may be partially due to decreasing ototoxic molecule uptake. The intracellular death pathways inhibition triggered by gentamicin might be also included as no blockage of gentamicin was observed. Our data suggest that Bendavia represents a novel otoprotective drug that might provide a therapeutic alternative for patients receiving aminoglycoside treatment.

Reduction-sensitive Paclitaxel Prodrug Self-assembled Nanoparticles with Tetrandrine Effectively Promote Synergistic Therapy Against Drug-sensitive and Multidrug-resistant Breast Cancer.

Codelivery of multiple drugs with complementary anticancer mechanisms by nanocarriers offers an effective strategy to treat cancers. Herein, conjugation (PTX-SS-VE) of paclitaxel (PTX) to vitamin E succinate (VE) self-assembled nanoparticles were used to load tetrandrine (TET) for combinational treatment against breast carcinoma. The ratio of PTX-SS-VE and TET was optimized. Compared with PTX, the TET/PTX-SS-VE coloaded nanoparticles (TPNPs) demonstrated superior cytotoxicity against both MCF-7 cells and MCF-7/Adr cells. TPNPs were facilitated to release PTX and TET under a highly reductive environment in tumor cells through the in vitro simulative release study. Cell apoptosis study and Western blotting analysis exhibited TPNPs could significantly increase cell apoptosis via modulating the levels of Bcl-2 protein and Caspase-3, which might be triggered by excess cellular reactive oxygen species (ROS) production through an intracellular ROS detection test. Cellular uptake study showed that TET could increase PTX accumulation in MCF-7/Adr cells but not in MCF-7 cells, which explained stronger synergetic efficacy of TPNPs on MCF-7/Adr cells. Overall, encapsulation of hydrophobic drugs, such as TET, in reduction-sensitive PTX-SS-VE nanoparticles provides a prospective strategy to effectively overcome the multidrug resistance of tumor cells in a synergistic manner. Such a uniquely small molecular weight prodrug-nanocarrier opens up new perspectives for the development of nanomedicines.

Supercritical fluid chromatography coupled with tandem mass spectrometry: A high-efficiency detection technique to quantify Taxane drugs in whole-blood samples.

We present a technique to rapid determine taxane in blood samples by supercritical fluid chromatography together with mass spectrometry. The aim of this study was to develop a supercritical fluid chromatography with mass spectrometry method for the analysis of paclitaxel, cabazitaxel, and docetaxel in whole-blood samples of rats. Liquid-dry matrix spot extraction was selected in sample preparation procedure. Supercritical fluid chromatography separation of paclitaxel, cabazitaxel, docetaxel, and glyburide (internal standard) was accomplished within 3 min by using the gradient mobile phase consisted of methanol as the compensation solvent and carbon dioxide at a flow rate of 1.0 mL/min. The method was validated regarding specificity, the lower limit of quantification, repeatability, and reproducibility of quantification, extraction recovery, and matrix effects. The lower limit of quantification was found to be 10 ng/mL since it exhibited acceptable precision and accuracy at the corresponding level. All interday accuracies and precisions were within the accepted criteria of ±15% of the nominal value and within ±20% at the lower limit of quantification, implying that the method was reliable and reproducible. In conclusion, this method is a promising tool to support and improve preclinical or clinical pharmacokinetic studies with the taxanes anticancer drugs.

Absolute oral bioavailability of fenofibric acid and choline fenofibrate in rats determined by ultra-performance liquid chromatography tandem mass spectrometry.

Choline fenofibrate is the choline salt of fenofibric acid, which releases free fenofibric acid in the gastrointestinal tract. To estimate the absolute oral bioavailability of fenofibric acid and choline fenofibrate, a novel and sensitive UPLC-MS/MS method with liquid-liquid extraction procedure was developed for the determination of fenofibric acid in rat plasma. The separation was achieved on a Phenomenex Kinetex C18 column (50 × 2.1 mm, 2.6 µm) containing 2 mm ammonium acetate-methanol with a gradient elution program. Validations of this method including specificity, sensitivity (limit of quantification, 5 ng/mL), linearity (0.005-10 µg/mL), accuracy (within ±4.3%), precision (intra- and inter-day coefficient of variation <11.3%), recovery (94.9-105.2% for fenofibric acid), matrix effect, stability and dilution, were all within acceptable limits. This method successfully supported the determination of fenofibric acid and choline fenofibrate. The absolute oral bioavailability was 93.4% for choline fenofibrate and 40.0% for fenofibric acid. These results suggested that choline fenofibrate and fenofibric acid had a better in vivo pharmacokinetic behavior than that of fenofibrate. The two new orally administrated pharmaceuticals, fenofibric acid and choline fenofibrate, can be developed as alternatives to fenofibrate.

A novel eye drop of alpha tocopherol to prevent ocular oxidant damage: improve the stability and ocular efficacy.

The aim of this study was to design novel mixed micelles as an ophthalmic delivery system for alpha-tocopherol (TOC) to prevent its degradation and improve ocular efficacy. The nonionic polymers, Polyoxyl 15 Hydroxystearate (Solutol® HS15) and Pluronic® F127, were discovered to be the most effective agents for retaining the activity and solubilization of TOC, respectively. Prepared by a thin-film hydration method, HS15/Pluronic® F127 yielded good encapsulation percentages of TOC, with a 27.7% drug loading efficiency. Incorporation of cetalkonium chloride (CKC) into HS15/Pluronic® F127 mixed micelles made the zeta potential of the micelles +17 mV, potentially prolonging the residence time of formulations on ocular surfaces. The optimized micelle preparation remained stable when diluted in a synthetic tear solution. It is known that the antioxidant ability of TOC in typical formulations reduces to around 85% of its initial value after 1 month when stored at 4 or 25 °C under an air atmosphere, which limits ophthalmic applications to less than 1 month. However, encapsulated TOC in investigated micelles remained stable for at least 6 months when sealed with N2. Finally, the cationic micelles were well tolerated after multiple administrations in rabbits, and they improved ocular accumulation of TOC. Taken together, these data suggest that the optimized micelle preparations described in this study may be suitable drug carriers for the treatment of ocular oxidant damage.

Studies on the in vitro and in vivo degradation behavior of amino acid derivative-based organogels.

The in vitro degradation behavior of organogel with different gelators based on amino acid was investigated in detail. Two methods were applied in this research: weighting method and high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) method, which was established for the first time. Their degradation behaviors in vivo were investigated by varying the kind and concentration of gelators via subcutaneous implantation. The results showed that the stronger the gelation ability or the higher the gelator concentration, the slower the degradation rate of organogel. Moreover, the organogel prepared by oils with longer alkyl length degraded slower than that of the shorter ones, which also decreased in thermal stability and mechanical strength. The investigation on degradation process showed that the degradation rate was mainly controlled by the collapse of network structure formed by gelators. In conclusion, organogel had a tunable degradation rate through altering the gelator type, oil type and the gelator concentration. It remains a promising candidate for subcutaneous in-situ implant as drug delivery vehicle.

Dual drug load and release behavior on ion-exchange fiber: influencing factors and prediction method for precise control of the loading amount.

Ion-exchange fiber undergoes a stoichiometric exchange reaction and has large exchange capability, which makes it a promising candidate as a multiple drug carrier. Because combinatorial effects can act synergistically, additively or antagonistically depending on the ratio of the agents being combined, the objective of this study was to learn the dual drug loading of ion-exchange fiber and develop a mathematical method for precisely control of the loading amount. Atenolol and Gatifloxacin, with different loading behaviors into strong cationic ion-exchange fiber ZB-1, were used to build a representative of dual loading. Not suitable pH value of drug solutions could make simultaneous loading fail, while the change of drug solution volume hardly affected the equilibrium. Ion-exchange groups occupied by the drug which owned lower affinity to fiber could be grabbed by the higher affinity drug, indicating the existence of competition between drugs. Thermodynamic model was introduced to guide the loading prediction and a favorable relevance had been shown between determined and predicted data. The release behaviors of each drug from dual drug-fiber complex were similar to those from single drug-fiber complexes.

Biological artificial fluid-induced non-lamellar phases in glyceryl monooleate: the kinetics pathway and its digestive process by bile salts.

BACKGROUND: The cubic (Q(II)) phase is a promising sustained-release system. However, its rigid gel-like propensity is highly viscous, which makes it difficult to handle in pharmaceutical applications. To circumvent this problem, a less viscous lamellar (L(α)) phase that could spontaneously transform to Q(II) phase by the introduction of water or biological artificial fluid can be used. However, the kinetics pathway of phase transition, susceptibility to digestive processes and impact of the transition on drug release are not yet well understood. METHOD: We investigated various biological artificial fluid-induced L(α) to inverse Q(II) phase transition over time in glyceryl monooleate (GMO) by water penetration scan and light polarizing microscopy. To reveal the structure stability, fluorescence spectroscopy studies were conducted using pyrene as a probe. Furthermore, the release mechanism of pyrene as a lipophilic drug model in the spontaneously formed Q(II) was investigated. RESULT: Although hexagonal (H(II)) mesophases occurred when phosphate buffered saline (PBS) 7.4, 0.1 M HCl or sodium taurocholate (NaTC) solutions were introduced to GMO at room temperature, they disappear with the exception of 0.1 M HCl at 37 °C. Compared with 25 °C, L(α) to Q(II) phase transition was in a faster rate as almost completely transforms were observed after 2 h post-immersion. The spontaneously formed mesophases were stable over 24 h immersions in PBS or pancreatic lipase solutions as proven by the extremely low fluorescence signal, however they were digestible by bile salts. This result indicated that digestion by bile salts was the major pathway instead of digestion by lipases. Moreover, pyrene fluorescence spectroscopy confirmed that the digestion by bile salts induced the formation of GMO-bile salt mixed micelles whose performance depended on the bile salt concentrations. This dependence influenced the drug release from the spontaneously formed Q(II) phase. CONCLUSION: All the results concluded that temperature, pH and ionic strength tendencies for the formation of non-lamellar structures greatly influenced the self-assembly process, thereby affecting the final mesophase structure. The results of this study are important to understand the lamellar to non-lamellar lipid-phase transitions and their possible pharmaceutical applications.

Evaluation of intratympanic formulations for inner ear delivery: methodology and sustained release formulation testing.

A convenient and efficient in vitro diffusion cell method to evaluate formulations for inner ear delivery via the intratympanic route is currently not available. The existing in vitro diffusion cell systems commonly used to evaluate drug formulations do not resemble the physical dimensions of the middle ear and round window membrane. The objectives of this study were to examine a modified in vitro diffusion cell system of a small diffusion area for studying sustained release formulations in inner ear drug delivery and to identify a formulation for sustained drug delivery to the inner ear. Four formulations and a control were examined in this study using cidofovir as the model drug. Drug release from the formulations in the modified diffusion cell system was slower than that in the conventional diffusion cell system due to the decrease in the diffusion surface area of the modified diffusion cell system. The modified diffusion cell system was able to show different drug release behaviors among the formulations and allowed formulation evaluation better than the conventional diffusion cell system. Among the formulations investigated, poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) triblock copolymer systems provided the longest sustained drug delivery, probably due to their rigid gel structures and/or polymer-to-cidofovir interactions.

Improved oral bioavailability of glyburide by a self-nanoemulsifying drug delivery system.

AIM: The present study aimed at the development and characterisation of self-nanoemulsifying drug delivery system (SNEDDS) to improve the oral bioavailability of poorly soluble glyburide. METHODS: The solubility of glyburide was determined in various oils, surfactants and co-surfactants which were grouped into two different combinations to construct ternary phase diagrams. The formulations were evaluated for emulsification time, droplet size, zeta-potential, electrical conductivity and stability of nanoemulsions. RESULT: The optimised SNEDDS loading with 5 mg/g glyburide comprised 55% Cremophor® RH 40, 15% propanediol and 30% Miglyol® 812, which rapidly formed fine oil-in-water nanoemulsions with 46 ± 4 nm particle size. Compared with the commercial micronised tablets (Glynase®PresTab®), enhanced in vitro release profiles of SNEDDS were observed, resulting in the 1.5-fold increase of AUC following oral administration of SNEDDS in fasting beagle dogs. CONCLUSIONS: These results indicated that SNEDDS is a promising drug delivery system for increasing the oral bioavailability of glyburide.

Development of novel N-aryl-2,4-bithiazole-2-amine-based CYP1B1 degraders for reversing drug resistance.

Extrahepatic cytochrome P450 1B1 (CYP1B1), which is highly expressed in non-small cell lung cancer, is an attractive target for cancer prevention, therapy, and overcoming drug resistance. Historically, CYP1B1 inhibition has been the primary therapeutic approach for treating CYP1B1-related malignancies, but its success has been limited. This study introduced CYP1B1 degradation as an alternative strategy to counter drug resistance and metastasis in CYP1B1-overexpressing non-small cell lung cancer A549/Taxol cells via a PROTAC strategy. Our investigation revealed that the identification of the potent CYP1B1 degrader PV2, achieving DC50 values of 1.0 nM and inducing >90 % CYP1B1 degradation at concentrations as low as 10 nM in A549/Taxol cells. Importantly, PV2 enhanced the sensitivity of the A549/Taxol subline to Taxol, possibly due to its stronger inhibitory effects on P-gp through CYP1B1 degradation. Additionally, compared to the CYP1B1 inhibitor A1, PV2 effectively suppressed the migration and invasion of A549/Taxol cells by inhibiting the FAK/SRC and EMT pathways. These findings hold promise for a novel therapy targeting advanced CYP1B1+ non-small cell lung cancer.

Fe3+ mediated shikonin and PPA coloaded liposomes induce robust immunogenic cell death by integrating ROS enhancement and GSH depletion.

Reactive oxygen species (ROS) can not only induce cellular oxidative stress, but also trigger antitumor immune response. However, single ROS generated therapy is usually not enough to induce efficient antitumor immune response. Furthermore, the adaptive antioxidant mechanisms coupled with overexpressed ROS can also decrease the antitumor capacity of ROS therapy. To circumvent this problem, we designed a synergistic strategy for inducing robust ROS based ICD effect by constructing a coloaded liposomes (PPA, Pyropheophorbide-alpha and SHK, shikonin) with Fe3+ gradient to simultaneously enhance ROS mediated oxidative stress and glutathione depletion. Interestingly, the coloaded liposome possesses an acid/GSH dual triggered release profile. More importantly, with the help of depleting GSH, LipoPS (coloaded liposome of SHK and PPA) can excite robust ROS and demonstrate synergistic antitumor efficacy with amplified ICD effect. Summarized, the established coloaded liposome LipoPS exhibits good therapeutic security and synergistic antitumor effect with strong antitumor immune activation, providing potential for further development.

Design and evaluation of enteric-coated tablets for rifampicin and isoniazid combinations.

In order to improve the bioavailability of rifampicin (RIF) from rifampicin and isoniazid (INH) combination formulations, the physicochemical characteristics of RIF, stability of RIF in different pH buffers in the presence of INH, as well as the effect of particle size of RIF materials on the dissolution rate were investigated. On the basis of the above examinations, enteric-coated tablets for RIF and INH combinations were designed and prepared. RIF showed low solubility and high apparent distribution coefficient in the intestinal pH (pH 4.0-7.4). With the decrease in pH, the degradation of RIF increase and the presence of INH deepen the degradation. Enteric-coated tablets were prepared after grinding the RIF materials by dry granulation technique. The pharmacokinetics of RIF and INH of self-made enteric-coated tablets in dogs were studied by comparing with the reference tablets. The AUC(0-48) of RIF in both reference and test tablets were 304.77 ± 42.27 and 353.79 ± 31.63 µg·h·mL(-1), respectively. The AUC(0-48) of INH in both reference and test tablets were 17.14 ± 8.59 and 19.62 ± 10.57 µg·h·mL(-1), respectively. Enteric-coated tablets may minimize the decomposition of RIF in gastrointestinal tract and improve the bioavailability.

Ligand-free high loading capacity ursolic acid self-carried nanovesicles enable hepatocyte targeting via absorbing apolipoproteins.

Ursolic acid (UA), a natural pentacyclic terpenoid carboxylic acid that can exert a potent hepatoprotective activity, has been developed into various types of nanoparticles to improve its pharmacological effects, however, the phagocytosis of nanoparticles by Kupffer cells greatly limits its efficacy. Herein, UA/Tween 80 nanovesicles (V-UA) were constructed and despite its simple composition, it fulfills multiple functions simultaneously: UA served as not only an active ingredient in the nanovesicle drug delivery system, but also acts as part of the carrier to stabilize UA/Tween 80 nanostructure; with a molar ratio of UA to Tween 80 up to 2:1, the formulation possesses a significant advantage of higher drug loading capacity; relative to liposomal UA (Lipo-UA), a conditional cellular uptake and higher accumulation of V-UA in hepatocytes provide insights into the hepatocytes targeting mechanisms of this nanovesicles. Favorable hepatocyte targeting ability also facilitates the treatment of liver diseases, which was well validated in three liver disease models.

Biomimetic virus-like mesoporous silica nanoparticles improved cellular internalization for co-delivery of antigen and agonist to enhance Tumor immunotherapy.

Nanocarrier antigen-drug delivery system interacts specifically with immune cells and provides intelligent delivery modes to improve antigen delivery efficiency and facilitate immune progression. However, these nanoparticles often have weak adhesion to cells, followed by insufficient cell absorption, leading to a failed immune response. Inspired by the structure and function of viruses, virus-like mesoporous silica nanoparticles (VMSNs) were prepared by simulating the surface structure, centripetal-radialized spike structure and rough surface topology of the virus and co-acted with the toll-like receptor 7/8 agonist imiquimod (IMQ) and antigens oocyte albumin (OVA). Compared to the conventional spherical mesoporous silica nanoparticles (MSNs), VMSNs which was proven to be biocompatible in both cellular and in vivo level, had higher cell invasion ability and unique endocytosis pathway that was released from lysosomes and promoted antigen cross-expression. Furthermore, VMSNs effectively inhibited B16-OVA tumor growth by activating DCs maturation and increasing the proportion of CD8+ T cells. This work demonstrated that virus-like mesoporous silica nanoparticles co-supply OVA and IMQ, could induce potent tumor immune responses and inhibit tumor growth as a consequence of the surface spike structure induces a robust cellular immune response, and undoubtedly provided a good basis for further optimizing the nanovaccine delivery system.