Bound-Extended Mode Transition in Type-II Synthetic Photonic Weyl Heterostructures.

Photonic structures with Weyl points (WPs), including type I and type II, promise nontrivial surface modes and intriguing light manipulations for their three-dimensional topological bands. While previous studies mainly focus on exploring WPs in a uniform Weyl structure, here we establish Weyl heterostructures (i.e., a nonuniform Weyl lattice) with different rotational orientations in the synthetic dimension by nanostructured photonic waveguides. In this work, we unveil a transition between bound and extended modes on the interface of type-II Weyl heterostructures by tuning their rotational phases, despite the reversed topological order across the interface. This mode transition is also manifested from the total transmission to total reflection at the interface. All of these unconventional effects are attributed to the tilted dispersion of type-II Weyl band structure that can lead to mismatched bands and gaps across the interface. As a comparison, the type-I Weyl heterostructures lack the phase transition due to the untilted band structure. This work establishes a flexible scheme of artificial Weyl heterostructures that opens a new avenue toward high-dimensional topological effects and significantly enhances our capabilities in on-chip light manipulations.

Perfect Excitation of Topological States by Supersymmetric Waveguides.

Topological photonic states provide intriguing strategies for robust light manipulations, however, it remains challenging to perfectly excite these topological eigenstates due to their complicated mode profiles. In this work, we propose to realize the exact eigenmode of the topological edge states by supersymmetric (SUSY) structures. By adiabatically transforming the SUSY partner to its main topological structure, the edge modes can be perfectly excited with simple single-site input. We experimentally verify our strategy in integrated silicon waveguides in telecommunication wavelength, showing a broad working bandwidth. Moreover, a shortcut-to-adiabaticity strategy is further applied to speed up the adiabatic pump process by inverse-design approaches, thus enabling fast mode evolutions and leading to reduced device size. Our method is universal and beneficial to the topology-based or complex eigenmodes systems, ranging from photonics and microwaves to cold atoms and acoustics.

Proton therapy and limited surgery for paediatric and adolescent patients with craniopharyngioma (RT2CR): a single-arm, phase 2 study.

BACKGROUND: Compared with photon therapy, proton therapy reduces exposure of normal brain tissue in patients with craniopharyngioma, which might reduce cognitive deficits associated with radiotherapy. Because there are known physical differences between the two methods of radiotherapy, we aimed to estimate progression-free survival and overall survival distributions for paediatric and adolescent patients with craniopharyngioma treated with limited surgery and proton therapy, while monitoring for excessive CNS toxicity. METHODS: In this single-arm, phase 2 study, patients with craniopharyngioma at St Jude Children's Research Hospital (Memphis TN, USA) and University of Florida Health Proton Therapy Institute (Jacksonville, FL, USA) were recruited. Patients were eligible if they were aged 0-21 years at the time of enrolment and had not been treated with previous radiotherapeutic or intracystic therapies. Eligible patients were treated using passively scattered proton beams, 54 Gy (relative biological effect), and a 0·5 cm clinical target volume margin. Surgical treatment was individualised before proton therapy and included no surgery, single procedures with catheter and Ommaya reservoir placement through a burr hole or craniotomy, endoscopic resection, trans-sphenoidal resection, craniotomy, or multiple procedure types. After completing treatment, patients were evaluated clinically and by neuroimaging for tumour progression and evidence of necrosis, vasculopathy, permanent neurological deficits, vision loss, and endocrinopathy. Neurocognitive tests were administered at baseline and once a year for 5 years. Outcomes were compared with a historical cohort treated with surgery and photon therapy. The coprimary endpoints were progression-free survival and overall survival. Progression was defined as an increase in tumour dimensions on successive imaging evaluations more than 2 years after treatment. Survival and safety were also assessed in all patients who received photon therapy and limited surgery. This study is registered with ClinicalTrials.gov, NCT01419067. FINDINGS: Between Aug 22, 2011, and Jan 19, 2016, 94 patients were enrolled and treated with surgery and proton therapy, of whom 49 (52%) were female, 45 (48%) were male, 62 (66%) were White, 16 (17%) were Black, two (2%) were Asian, and 14 (15%) were other races, and median age was 9·39 years (IQR 6·39-13·38) at the time of radiotherapy. As of data cutoff (Feb 2, 2022), median follow-up was 7·52 years (IQR 6·28-8·53) for patients who did not have progression and 7·62 years (IQR 6·48-8·54) for the full cohort of 94 patients. 3-year progression-free survival was 96·8% (95% CI 90·4-99·0; p=0·89), with progression occurring in three of 94 patients. No deaths occurred at 3 years, such that overall survival was 100%. At 5 years, necrosis had occurred in two (2%) of 94 patients, severe vasculopathy in four (4%), and permanent neurological conditions in three (3%); decline in vision from normal to abnormal occurred in four (7%) of 54 patients with normal vision at baseline. The most common grade 3-4 adverse events were headache (six [6%] of 94 patients), seizure (five [5%]), and vascular disorders (six [6%]). No deaths occurred as of data cutoff. INTERPRETATION: Proton therapy did not improve survival outcomes in paediatric and adolescent patients with craniopharyngioma compared with a historical cohort, and severe complication rates were similar. However, cognitive outcomes with proton therapy were improved over photon therapy. Children and adolescents treated for craniopharyngioma using limited surgery and post-operative proton therapy have a high rate of tumour control and low rate of severe complications. The outcomes achieved with this treatment represent a new benchmark to which other regimens can be compared. FUNDING: American Lebanese Syrian Associated Charities, American Cancer Society, the US National Cancer Institute, and Research to Prevent Blindness.

Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Mannose, a common monosaccharide taken up by cells through the same transporters as glucose, has been shown to induce growth retardation and enhance cell death in response to chemotherapy in several cancers, including PDAC. However, the molecular targets and mechanisms underlying mannose's action against PDAC are not well understood. In this study, we used an integrative approach of network pharmacology, bioinformatics analysis, and experimental verification to investigate the pharmacological targets and mechanisms of mannose against PDAC. Our results showed that the protein Src is a key target of mannose in PDAC. Additionally, computational analysis revealed that mannose is a highly soluble compound that meets Lipinski's rule of five and that the expression of its target molecules is correlated with survival rates and prognosis in PDAC patients. Finally, we validated our findings through in vitro and in vivo experiments. In conclusion, our study provides evidence that mannose plays a critical role in inhibiting PDAC growth by targeting Src, suggesting that it may be a promising therapeutic candidate for PDAC.

Observation of Weyl Interface States in Non-Hermitian Synthetic Photonic Systems.

Weyl medium has triggered remarkable interest owing to its nontrivial topological edge states in 3D photonic band structures that were mainly revealed as surface modes yet. It is undoubted that the connection of two different Weyl media will give rise to more fruitful physics at their interface, while they face extreme difficulty in high-dimensional lattice matching. Here, we successfully demonstrate the non-Hermitian Weyl interface physics in complex synthetic parameter space, which is implemented in a loss-controlled silicon waveguide array. By establishing non-Hermitian Hamiltonian in the parameter space, new Weyl interfaces with distinct topological origins are predicted and experimentally observed in silicon waveguides. Significantly, our Letter exploits the non-Hermitian parameter to create the synthetic dimension by manipulating the non-Hermitian order, which successfully circumvents the difficulty in lattice matching for high-dimensional interfaces. The revealed rich topological Weyl interface states and their phase transitions in silicon waveguide platform further imply potentials in chip-scale photonics integrations.

Outcome and safety of intracardiac echocardiography guided left atrial appendage closure within zero-fluoroscopy atrial fibrillation ablation procedures.

BACKGROUND: Simultaneous atrial fibrillation (AF) catheter ablation and left atrial appendage closure (LAAC) are sometimes recommended for both rhythm control and stroke prevention. However, the advantages of intracardiac echocardiography (ICE) guidance for this combined procedure have been scarcely reported. We aim to evaluate the clinical outcomes and safety of ICE-guided LAAC within a zero-fluoroscopy catheter ablation procedure. METHODS AND RESULTS: From April 2019 to April 2020, 56 patients with symptomatic AF underwent concomitant catheter ablation and LAAC. ICE with a multi-angled imaging protocol mimicking the TEE echo windows was used to guide LAAC. Successful radiofrequency catheter ablation and LAAC were achieved in all patients. Procedure-related adverse event rate was 3.6%. During the 12-month follow-up, 75.0% of patients became free of arrhythmia recurrences and oral anticoagulants were discontinued in 96.4% of patients. No ischemic stroke occurred despite two cases of device-related thrombosis versus an expected stroke rate of 4.8% based on the CHA2 DS2 -VASc score. The overall major bleeding events rate was 1.8%, which represented a relative reduction of 68% versus an expected bleeding rate of 5.7% based on the HAS-BLED score of the patient cohort. The incidence of iatrogenic atrial septal defect secondary to single transseptal access dropped from 57.9% at 2 months to 4.2% at 12 months TEE follow-up. CONCLUSION: The combination of catheter ablation and LAAC under ICE guidance was safe and effective in AF patients with high stroke risk. ICE with our novel protocol was technically feasible for comprehensive and systematic assessment of device implantation.

Conduction system pacing following septal myectomy: Insights into site of conduction block.

INTRODUCTION: Septal myectomy for obstructive hypertrophic cardiomyopathy (HCM) is associated with conduction block; however, the electrophysiological characteristics of conduction block have not been well characterized. The aim of study was to assess the feasibility and safety of His bundle pacing (HBP) and left bundle branch area pacing (LBBAP) in patients with septal myectomy-associated conduction block. METHODS AND RESULTS: Patients with HCM and indications for pacing or cardiac resynchronization therapy after septal myectomy were included. Electrophysiological mapping was performed to identify the site of block. The success rates and pacing characteristics of HBP and LBBAP were also recorded. The echocardiographic data and complications were documented and tracked during follow-up. Ten patients with atrioventricular block (AVB) or left bundle branch block (LBBB) post-myectomy were included in the study. The site of block was infranodal in the nine patients with AVB. HBP failed due to the lack of distal His bundle capture (N = 7) or LBBB correction (N = 3). LBBAP was successful in nine patients and failed in one. QRS duration narrowed from 163.3 ± 16.6 ms after surgery to 123.6 ± 15.8 ms during LBBAP (p < .001). The mean depth of the leads was 13.3 ± 4.0 mm (range from 10 to 20 mm). At a mean follow-up of 5.3 ± 3.9 months, pacing parameters and left ventricular ejection fraction remained stable. CONCLUSIONS: Electrophysiological mapping revealed that the site of block was infra-Hisian and not correctable with HBP in patients with HCM post-myectomy. LBBAP appears to be a more feasible physiological strategy for these patients.

Anomalous π modes by Floquet engineering in optical lattices with long-range coupling.

Photonic Floquet topological insulators provide a powerful tool to manipulate the optical fields, which have been extensively studied with only nearest-neighbor coupling. Here, we demonstrate that nontrivial Floquet topological phase and photonic π modes are brought from long-range coupling in a one-dimensional periodically driven optical lattice. Interestingly, the long-range coupling is found to give rise to new Floquet π modes that do not exist in the traditional Floquet lattices. We interpret the underlying physics by analyzing the replica bands, which shows quasienergies band crossing and reopening of new nontrivial π gaps due to the long-range coupling. Our results provide a new route in manipulating optical topological modes by Floquet engineering with long-range coupling.

Dispersionless Coupling among Optical Waveguides by Artificial Gauge Field.

Coupling among closely packed waveguides is a common optical phenomenon, and plays an important role in optical routing and integration. Unfortunately, this coupling property is usually sensitive to the working wavelength and structure features that hinder the broadband and robust functions. Here, we report a new strategy utilizing an artificial gauge field (AGF) to engineer the coupling dispersion and realize a dispersionless coupling among waveguides with periodically bending modulation. The AGF-induced dispersionless coupling is experimentally verified in a silicon waveguide platform, which already has well-established broadband and robust routing functions (directional coupling and splitting), suggesting potential applications in integrated photonics. As examples, we further demonstrate a three-level-cascaded AGF waveguide network to route broadband light to desired ports with an overwhelming advantage over the conventional ones in comparison. Our method provides a new route of coupling dispersion control by AGF and benefits applications that fundamentally rely on waveguide coupling.

Photon versus proton whole ventricular radiotherapy for non-germinomatous germ cell tumors: A report from the Children's Oncology Group.

PURPOSE: To determine if proton therapy reduces doses to cranial organs at risk (OARs) as compared to photon therapy in children with non-germinomatous germ cell tumors (NGGCT) receiving whole ventricular radiotherapy (WVRT). METHODS AND MATERIALS: Dosimetric data for patients with NGGCT prospectively enrolled in stratum 1 of the Children's Oncology Group study ACNS1123 who received 30.6 Gy WVRT were compared. Target segmentation was standardized using a contouring atlas. Doses to cranial OARs were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were analyzed included mean dose and dose to 40% of the OAR volume (D40). RESULTS: Mean and D40 doses to the supratentorial brain, cerebellum, and bilateral temporal, parietal, and frontal lobes were statistically significantly lower amongst proton-treated patients, as compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3-mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. CONCLUSIONS: Children treated with proton therapy for WVRT had lower doses to normal brain structures, when compared to those treated with photon therapy. Proton therapy should be considered for patients receiving WVRT for NGGCT.

Atrial-His bundle pacing in fulminant myocarditis with ventricular arrhythmia: a case report.

BACKGROUND: Fulminant myocarditis is a clinical syndrome associated with threatening dysrhythmia which temporary pacemaker can be used for life-saving support. As a method of physiological pacing, His bundle pacing (HBP) maintain better cardiac synchronization than traditional right ventricular (RV) pacing. CASE PRESENTATION: It's a severe case of fulminant myocarditis in a 41-year-old patient who presented for recurrent arrhythmias with hemodynamic instability. Temporary His bundle pacing combined with optimal medical therapy and extracorporeal membrane oxygenators (ECMO) supported him through his critical period of hospitalization. CONCLUSIONS: During 1-year follow up, the cardiac function recovery was obvious without any pacing related complications. Echocardiography showed better atrioventricular and intra-ventricular synchronization during HBP in DDD mode. This is the first reported case of temporary His-purkinje conduction system pacing used for severe fulminant myocarditis.

Convergent Synthesis and Anti-Pancreatic Cancer Cell Growth Activity of a Highly Branched Heptadecasaccharide from Carthamus tinctorius.

Bioactive polysaccharides from natural resources target various biological processes and are increasingly used as potential target molecules for drug development. However, the accessibility of branched and long complex polysaccharide active domains with well-defined structures remains a major challenge. Herein we describe an efficient first total synthesis of a highly branched heptadecasaccharide moiety of the native bioactive galectin-3-targeting polysaccharide from Carthamus tinctorius L. as well as shorter fragments of the heptadecasaccharide. The key feature of the approach is that a photo-assisted convergent [6+4+7] one-pot coupling strategy enables rapid assembly of the heptadecasaccharide, whereby a photoremovable o-nitrobenzyl protecting group is used to generate the corresponding acceptor for glycosylation in situ upon ultraviolet radiation. Biological activity tests suggest that the heptadecasaccharide can target galectin-3 and inhibit pancreatic cancer cell growth.

Trichostatin A downregulates bromodomain and extra-terminal proteins to suppress osimertinib resistant non-small cell lung carcinoma.

BACKGROUND: The third-generation epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have shown significant therapeutic effects on patients with non-small cell lung carcinoma (NSCLC) who carry active EGFR mutations, as well as those who have developed acquired resistance to the first-generation of EGFR-TKIs due to the T790M mutation. However, most patients develop drug resistance after 8-10 months of treatment. Currently, the mechanism has not been well clarified, and new therapeutic strategies are urgently needed. METHODS: Osimertinib resistant cell lines were established by culturing sensitive cells in chronically increasing doses of osimertinib. The anticancer effect of reagents was examined both in vitro and in vivo using the sulforhodamine B assay and a xenograft mouse model. The molecular signals were detected by western blotting. The combination effect was analyzed using CompuSyn software. RESULTS: We found that bromodomain and extra-terminal proteins (BETs) were upregulated in osimertinib resistant (H1975-OR) cells compared with those in the paired parental cells (H1975-P), and that knockdown of BETs significantly inhibited the growth of H1975-OR cells. The BET inhibitor JQ1 also exhibited stronger growth-inhibitory effects on H1975-OR cells and a greater expression of BETs and the downstream effector c-Myc than were observed in H1975-P cells. The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) showed stronger growth suppression in H1975-OR cells than in H1975-P cells, but vorinostat, another HDAC inhibitor, showed equal inhibitory efficacy in both cell types. Consistently, downregulation of BET and c-Myc expression was greater with TSA than with vorinostat. TSA restrained the growth of H1975-OR and H1975-P xenograft tumors. The combination of TSA and JQ1 showed synergistic growth-inhibitory effects in parallel with decreased BET and c-Myc expression in both H1975-OR and H1975-P cells and in xenograft nude mouse models. BETs were not upregulated in osimertinib resistant HCC827 cells compared with parental cells, while TSA and vorinostat exhibited equal inhibitory effects on both cell types. CONCLUSION: Upregulation of BETs contributed to the osimertinib resistance of H1975 cells. TSA downregulated BET expression and enhanced the growth inhibitory effect of JQ1 both in vitro and in vivo. Our findings provided new strategies for the treatment of osimertinib resistance.

Conformation-Controlled Hydrogen-Bond-Mediated Aglycone Delivery Method for α-Xylosylation.

α-Xylosylated glycans and xylosyl derivatives are biomedically important molecules which show numerous bioactivities against infection, cancer, inflammation, and so on. Lacking an efficient α-xylosylation method, the synthesis of α-xyloside-containing molecules was full of challenges. Herein, a robust method is presented for selective α-xylosylation via combination of a rare conformation-controlled strategy and the hydrogen-bond-mediated aglycone delivery method. Various native branched α-xyloside structures necessitate an orthogonally protected xyloside, and a three-pot preparation method of the xylosyl donor was developed for this novel α-xylosylation method, which was further applied in the first synthesis of the side chain N of xyloglucan. This work provides an efficient α-xylosylation method which would make various α-xyloside structures achievable. The conformation-controlled strategy also has important reference to the chemistry of five-carbon pyranose.

New-onset intrinsic and paced QRS morphology of right bundle branch block pattern after atrioventricular nodal ablation: Longitudinal dissociation or anatomical bifurcation?

We performed left bundle pacing combined with atrioventricular nodal (AVN) ablation in a patient with persistent atrial fibrillation and refractory symptomatic heart failure. The major findings were new-onset intrinsic and paced QRS morphology of right bundle branch block (RBBB) pattern after AVN ablation which was performed at a more atrial site compared with the pacing site and the paced RBBB pattern could not be corrected regardless of the pacing output. Longitudinal dissociation cannot explain this observation, while anatomical separation could. We also confirm this was proximal left bundle pacing rather than His bundle pacing.

Electrophysiological characteristics and clinical values of left bundle branch current of injury in left bundle branch pacing.

BACKGROUND: Left bundle branch pacing (LBBP) is emerging as a novel option for physiological ventricular pacing. The impact of current of injury (COI) at left bundle branch (LBB) has not been previously evaluated. METHODS: Consecutive patients with QRS duration less than 120 milliseconds referred for LBBP in whom LBB potentials were recorded were included from August 2018 to March 2019. We recorded LBB COI during LBBP and assessed its impact on the pacing parameters and complications during implantation and at short term follow-up. RESULTS: A total of 115 patients with an identifiable LBB potential at implant were included. LBB COI was confirmed in 77 (67.0%) of these patients. Three types of LBB COI were observed. LBB was captured in all patients at a pacing threshold less than 1.5 V/0.5 ms in COI(+) patients, while present in only 29 patients without an LBB COI(-) (100% vs 76.3%; P < .001). There was no significant difference between COI(+) and COI(-) patients in LBB bundle capture threshold (0.64 ± 0.24 vs 0.74 ± 0.26 V/0.5 ms). Selective LBBP was more common in COI(+) group than COI(-) group (54.5% vs 0%; P < .001). Pacing parameters were stable and no lead perforation or dislodgements were observed during follow-up. CONCLUSIONS: LBB COI is commonly observed during LBBP in cases with an identifiable LBB potential and can be associated with a low LBB capture threshold and demonstrable selective capture of the LBB acutely and during follow-up. A COI does not preclude safe and stable LBBP pacing.

Novel left ventricular cardiac synchronization: left ventricular septal pacing or left bundle branch pacing?

It is well recognized that a high burden of right ventricular pacing results in deleterious clinical outcomes over the long term. His bundle pacing can achieve optimal ventricular synchronization; however, relatively high pacing thresholds, low R-wave amplitudes, and the long-term performance have been concerns. Recently, left ventricular (LV) septal endocardium pacing (LVSP) has demonstrated improved acute haemodynamics. Another novel technique of intraseptal left bundle branch pacing (LBBP) via transvenous approach has been adopted rapidly and has demonstrated its feasibility and effectiveness. This article reviews the clinical application and differences between LVSP and LBBP. Compared with LVSP, LBBP has strict criteria for left conduction system capture and lead location. In addition to LV septal capture it also stimulates the proximal left bundle branch, resulting in rapid and physiological LV activation. With a uniformity and standardization of the implant procedure and definitions, it may be possible to achieve widespread application of this form of physiological pacing.

Long-term performance and risk factors analysis after permanent His-bundle pacing and atrioventricular node ablation in patients with atrial fibrillation and heart failure.

AIMS: His-bundle pacing (HBP) combined with atrioventricular node (AVN) ablation has been demonstrated to be effective in patients with atrial fibrillation (AF) and heart failure (HF) during medium-term follow-up and there are limited data on the risk analysis of adverse prognosis in this population. In this study, we aimed to evaluate the long-term performance of HBP following AVN ablation in AF and HF. METHODS AND RESULTS: From August 2012 to December 2017, consecutive AF patients with HF and narrow QRS who underwent AVN ablation and HBP were enrolled. The clinical and echocardiographic data, pacing parameters, all-cause mortality, and heart failure hospitalization (HFH) were tracked. A total of 94 patients were enrolled (age 70.1 ± 10.5 years; male 57.4%). Acute HBP were achieved in 89 (94.7%) patients with successful permanent HBP combined with AVN ablation in 81 (86.2%) patients. Left ventricular ejection fraction (LVEF) improved from 44.9 ± 14.9% at baseline to 57.6 ± 12.5% during a median follow-up of 3.0 (IQR: 2.0-4.4) years (P < 0.001). Heart failure hospitalization or all-cause mortality occurred in 21 (25.9%) patients. The LVEF ≤ 40%, pulmonary artery systolic pressure (PASP) ≥40 mmHg, or serum creatinine (Scr) ≥97 µmol/L at baseline was significantly associated with higher composite endpoint of HFH or death (P < 0.05). The His capture threshold was 1.0 ± 0.7 V/0.5 ms at implant and remained stable during follow-up. CONCLUSION: His-bundle pacing combined with AVN ablation was effective in patients with AF and drug-refectory HF. High PASP, high Scr, or low LVEF at baseline was independent predictors of composite endpoint of all-cause mortality or HFH.

Marked reduction in haemoglobin levels secondary to ceftizoxime-induced immune haemolytic anaemia in diabetic patients.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced immune haemolytic anaemia (DIIHA) is rare and difficult to diagnose. In diabetic patients, the diagnosis of DIIHA is even harder. In the current study, we report on two cases of ceftizoxime-induced immune haemolytic anaemia in diabetic patients. CASE DESCRIPTION: Two diabetic patients (suffering from type 1 and type 2 diabetes mellitus, respectively) presented with rapid reduction in haemoglobin levels when exposed to ceftizoxime (2g q12h). They both achieved symptom improvement after switching to another antibiotic. WHAT IS NEW AND CONCLUSION: The persistently reduced haemoglobin levels in diabetic patients may contribute to DIIHA. Reviewing patients' medical records might provide some valuable clues as to the causes of DIIHA.

Targeted Codelivery of an Antigen and Dual Agonists by Hybrid Nanoparticles for Enhanced Cancer Immunotherapy.

Among approaches of current cancer immunotherapy, a dendritic cell (DC)-targeted vaccine based on nanotechnology could be a promising way to efficiently induce potent immune responses. To enhance DC targeting and vaccine efficiency, we included imiquimod (IMQ), a toll-like receptor 7/8 (TLR 7/8) agonist, and monophosphoryl lipid A (MPLA), a TLR4 agonist, to synthesize lipid-polymer hybrid nanoparticles using PCL-PEG-PCL and DOTAP (IMNPs) as well as DSPE-PEG-mannose (MAN-IMNPS). The spatiotemporal delivery of MPLA (within the outer lipid layer) to extracellular TLR4 and IMQ (in the hydrophobic core of NPs) to intracellular TLR7/8 can activate DCs synergistically to improve vaccine efficacy. Ovalbumin (OVA) as a model antigen was readily absorbed by positively charged DOTAP and showed a quick release in vitro. Our results demonstrated that this novel nanovaccine enhanced cellular uptake, cytokine production, and maturation of DCs. Compared with the quick metabolism of free OVA-agonists, the depot effect of OVA-IMNPs was observed, whereas MAN-OVA-IMNPs promoted trafficking to secondary lymphoid organs. After immunization with a subcutaneous injection, the nanovaccine, especially MAN-OVA-IMNPs, induced more antigen-specific CD8+ T cells, greater lymphocyte activation, stronger cross-presentation, and more generation of memory T cells, antibody, IFN-γ, and granzyme B. Prophylactic vaccination of MAN-OVA-IMNPs significantly delayed tumor development and prolonged the survival in mice. The therapeutic tumor challenge indicated that MAN-OVA-IMNPs prohibited tumor progression more efficiently than other formulations, and the combination with an immune checkpoint blockade further enhanced antitumor effects. Hence, the DC-targeted vaccine codelivery with IMQ and MPLA adjuvants by hybrid cationic nanoparticles in a spatiotemporal manner is a promising multifunctional antigen delivery system in cancer immunotherapy.