Comparison of reconstruction plates and miniplates in mandibular defect reconstruction with free iliac flap.

OBJECTIVE: Given the increasing demand for precise and reliable reconstructive techniques in maxillofacial surgery, we try to offer valuable insights for clinicians in selecting optimal fixation methods. MATERIALS AND METHODS: Patients were categorized into miniplate and reconstruction plate groups for accuracy and bone healing comparison. We measured gonial angle, intercondylar, intergonial and anterior-posterior distance for general accuracy and distance of segmental endpoint to the sagittal plane for partial accuracy. The bone healing rate of the two groups was compared with CT images at 3, 6 and 12 months after operation. RESULT: Considering directional indicators, the miniplate group exhibited a wider intercondylar distance than the reconstruction plate group (p = 0.029). At 6 months postoperatively, the miniplate group demonstrated a higher bone healing rate compared to the reconstruction plate group, with no significant differences at other time points. CONCLUSION: Over a nearly 5-year review, mandibular reconstruction with vascularized iliac bone flaps showed that reconstruction plates better maintained condylar position accuracy, while miniplates had superior bone healing rates at 6 months. No significant differences were found in other accuracy indices between the two plates. CLINICAL RELEVANCE: Clinicians' selection of fixation plates frequently depends on personal preference rather than evidence-based criteria. This study compares the precision and postoperative osseous healing outcomes of miniplates and reconstruction plates to provide a more scientifically grounded basis for clinical decision-making.

Extended King integral for modeling of parametric array loudspeakers with axisymmetric profiles.

Parametric array loudspeakers have been widely used in audio applications for generating directional audio beams. However, accurately calculating audio sound with a low computational load remains challenging, even for basic axisymmetric source profiles. This work addresses this challenge by extending the King integral in linear acoustics to incorporate both cumulative and local nonlinear effects, under the framework of the quasilinear solution without the paraxial approximation. The proposed method exploits the azimuthal symmetry in cylindrical coordinates to simplify modeling. To further improve computational efficacy, fast Hankel and Fourier transforms are employed for the radial and beam radiation directions, respectively. Numerical results with both uniform and focusing profiles demonstrate the advantages of the proposed approach over the traditional spherical wave expansion and direct integration methods, especially for larger aperture sizes. Specifically, for typical configurations with source aperture size of 0.2 m, we observe at least a 24-fold improvement in computational speed and a 227-fold reduction in memory requirements. These advancements allow us, for the first time, to present the sound field radiated by parametric array loudspeakers with a large aperture size of up to 0.5 m, without paraxial approximations. The implementation codes are available on https://github.com/ShaoZhe-LI/PAL_King.

Recent advances in pathogenesis, diagnosis, and therapeutic approaches for digestive system involvement in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of large amounts of autoantibodies and immune complex formation. Because of their atypical clinical symptoms, SLE patients with digestive system involvement may not be recognized or treated precisely and extensively. Clinicians should pay close attention to SLE with digestive system involvement, as these conditions can easily worsen the condition and possibly endanger the patient's life. In this review we summarized the pathogenesis, pathological characteristics, clinical manifestations, diagnosis, and therapies for digestive system involvement in SLE.

Dietary Intake of Branched-Chain Fatty Acids, Metabolic Parameters, High-Sensitivity C-Reactive Protein Levels, and Anthropometric Features Among Elite and Subelite Soccer Players.

BACKGROUND: Several studies have revealed the positive healthy impacts of branched-chain fatty acids (BCFAs). However, most of these studies evaluated the serum BCFAs in humans, or treatment with exogenous BCFAs in animal or in-vitro models and the health impacts of dietary BCFAs have not yet been studied. Due to positive effects of BCFAs in sport, in the current study, we aimed to investigate the association between dietary BCFAs and metabolic and inflammatory parameters among elite and subelite soccer players. METHODS: A cross-sectional study was carried out among 335 elite and subelite soccer players (196 male), aged between 20 and 45 years old. Soccer players were enrolled from 32 teams under the directive of The Chinese Football Association. Demographic, anthropometric, and dietary assessments were performed and laboratory measurement including serum lipids, glycemic markers, and high-sensitivity C-reactive protein was measured. RESULTS: Those with the highest dietary BCFAs consumption had higher appetite (p = .009). Also, high consumption of dietary BCFAs was associated with lower diastolic blood pressure (odds ratio: 0.958; confidence interval: 0.918-0.999; p = .046) and low high-sensitivity C-reactive protein concentrations in the third tertile of dietary BCFAs (odds ratio: 0.431; confidence interval: 0.300-0.618; p < .001). No other association between biochemical variables and dietary BCFAs was found. CONCLUSION: As shown in the current study, higher dietary BCFAs consumption was associated with lower diastolic blood pressure and inflammation. Due to very limited number of studies, further studies are needed to have a better perspective of these associations and their underlying mechanisms.

NNMT switches the proangiogenic phenotype of cancer-associated fibroblasts via epigenetically regulating ETS2/VEGFA axis.

Cancer-associated fibroblasts (CAFs) are known to promote angiogenesis in oral squamous cell carcinoma (OSCC). However, the epigenetic mechanisms through which CAFs facilitate angiogenesis within the tumor microenvironment are still poorly characterized. Nicotinamide N'-methyltransferase (NNMT), a member of the N-methyltransferase family, was found to be a key molecule in the activation of CAFs. This study shows that NNMT in fibroblasts contributes to angiogenesis and tumor growth through an epigenetic reprogramming-ETS2-VEGFA signaling axis in OSCC. Single-cell RNA Sequencing (scRNA-seq) analysis suggests that NNMT is mainly highly expressed in fibroblasts of head and neck squamous cell carcinoma (HNSCC). Moreover, analysis of the TCGA database and multiple immunohistochemical staining of clinical samples also identified a positive correlation between NNMT and tumor angiogenesis. This research further employed an assembled organoid model and a fibroblast-endothelial cell co-culture model to authenticate the proangiogenic ability of NNMT. At the molecular level, high expression of NNMT in CAFs was found to promote ETS2 expression by regulating H3K27 methylation level through mediating methylation deposition. Furthermore, ETS2 was verified to be an activating transcription factor of VEGFA in this study. Collectively, our findings delineate an epigenetic molecular regulatory network of angiogenesis and provide a theoretical basis for exploring new targets and clinical strategy in OSCC.

EphA2 promotes the transcription of KLF4 to facilitate stemness in oral squamous cell carcinoma.

Ephrin receptor A2 (EphA2), a member of the Ephrin receptor family, is closely related to the progression of oral squamous cell carcinoma (OSCC). Cancer stem cells (CSCs) play essential roles in OSCC development and occurrence. The underlying mechanisms between EphA2 and CSCs, however, are not yet fully understood. Here, we found that EphA2 was overexpressed in OSCC tissues and was associated with poor prognosis. Knockdown of EphA2 dampened the CSC phenotype and the tumour-initiating frequency of OSCC cells. Crucially, the effects of EphA2 on the CSC phenotype relied on KLF4, a key transcription factor for CSCs. Mechanistically, EphA2 activated the ERK signalling pathway, promoting the nuclear translocation of YAP. Subsequently, YAP was bound to TEAD3, leading to the transcription of KLF4. Overall, our findings revealed that EphA2 can enhance the stemness of OSCC cells, and this study identified the EphA2/KLF4 axis as a potential target for treating OSCC.

Odontogenic carcinoma with dentinoid: case report and literature review of a rare entity.

BACKGROUND: Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. CASE PRESENTATION: This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and ß-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. CONCLUSIONS: OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

The potential therapeutic targets of glutamine metabolism in head and neck squamous cell carcinoma.

Targeting metabolic reprogramming may be an effective strategy to enhance cancer treatment efficacy. Glutamine serves as a vital nutrient for cancer cells. Inhibiting glutamine metabolism has shown promise in preventing tumor growth both in vivo and in vitro through various mechanisms. Therefore, this review collates recent scientific literature concerning the correlation between glutamine metabolism and cancer treatment. Novel treatment modalities based on amino acid transporters, metabolites, and glutaminase are discussed. Moreover, we demonstrate the relationship between glutamine metabolism and tumor proliferation, drug resistance, and the tumor immune microenvironment, offering new perspectives for the clinical treatment of head and neck squamous cell carcinoma, particularly for combined therapies. Identifying innovative approaches for enhancing the efficacy of glutamine-based metabolic therapy is crucial to improving HNSCC treatment.

Transboundary migration of Loxostege sticticalis (Lepidoptera: Crambidae) among China, Russia and Mongolia.

BACKGROUND: The beet webworm, Loxostege sticticalis, a worldwide pest of many crops, performs a seasonal migration, causing periodic outbreaks in Asia, Europe and North America. Although long-distance migration is well documented in China, patterns of transboundary migration among China, Russia and Mongolia are largely unknown. We performed a phase analysis of L. sticticalis periodic outbreaks among three countries based on 30 years of historical population data, analyzed the wind systems during migration over boundary regions, and traced the migratory routes in a case study of outbreaks in 2008 by trajectory simulation. RESULTS: Highly synchronized outbreak years of L. sticticalis were observed between China and Mongolia, China and eastern Siberia, China and western Siberia, Mongolia and eastern Siberia, eastern Siberia and western Siberia from 1978 to 2008, indicating possible transboundary migration between these regions. Winds at 300-600 m altitude, where adult migration usually occurs, also showed a high probability of northwestern winds in Haila'er (China), Chita (Russia) and Choybalsan (Mongolia), favoring successful adult migration from these areas to northern and northeastern China. Back trajectory analysis further showed that the first-generation adults that caused the severe outbreak of second-generation larvae in 2008 originated from eastern Siberia, eastern Mongolia, and the boundary regions of China-Russia and China-Mongolia. CONCLUSION: Our findings demonstrated that the source of L. sticticalis outbreaks in northern China was closely related to the outbreaks in Siberia and Mongolia via long-distance transboundary windborne migration. This information will help guide international monitoring and management strategies against this notorious pest. © 2024 Society of Chemical Industry.

Comparative analysis of GoPro and digital cameras in head and neck flap harvesting surgery video documentation: an innovative and efficient method for surgical education.

BACKGROUND: An urgent need exists for innovative surgical video recording techniques in head and neck reconstructive surgeries, particularly in low- and middle-income countries where a surge in surgical procedures necessitates more skilled surgeons. This demand, significantly intensified by the COVID-19 pandemic, highlights the critical role of surgical videos in medical education. We aimed to identify a straightforward, high-quality approach to recording surgical videos at a low economic cost in the operating room, thereby contributing to enhanced patient care. METHODS: The recording was comprised of six head and neck flap harvesting surgeries using GoPro or two types of digital cameras. Data were extracted from the recorded videos and their subsequent editing process. Some of the participants were subsequently interviewed. RESULTS: Both cameras, set at 4 K resolution and 30 frames per second (fps), produced satisfactory results. The GoPro, worn on the surgeon's head, moves in sync with the surgeon, offering a unique first-person perspective of the operation without needing an additional assistant. Though cost-effective and efficient, it lacks a zoom feature essential for close-up views. In contrast, while requiring occasional repositioning, the digital camera captures finer anatomical details due to its superior image quality and zoom capabilities. CONCLUSION: Merging these two systems could significantly advance the field of surgical video recording. This innovation holds promise for enhancing technical communication and bolstering video-based medical education, potentially addressing the global shortage of specialized surgeons.

Application of PRI-E-a combined learning method in oral and maxillofacial oncology education.

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.

Enhanced lipid biosynthesis in oral squamous cell carcinoma cancer-associated fibroblasts contributes to tumor progression: Role of IL8/AKT/p-ACLY axis.

Lipid metabolic reprogramming of tumor cells has been proven to play a critical role in tumor initiation and development. However, lipid metabolism in cancer-associated fibroblasts (CAFs) has rarely been studied, particularly in CAFs of oral squamous cell carcinoma (OSCC). Additionally, the molecular mechanism by which tumor cells regulate lipid metabolism in fibroblasts is unclear. In this study, we found that phosphorylated ATP citrate lyase (p-ACLY), a key lipid metabolic enzyme, was upregulated in OSCC CAFs. Compared to paracancerous normal fibroblasts, CAFs showed enhanced lipid synthesis, such as elevated cytosolic acetyl-CoA level and accumulation of lipid droplets. Conversely, reduction of p-ACLY level blocked this biological process. In addition, blocking lipid synthesis in CAFs or inhibiting fatty acid uptake by OSCC cells reduced the promotive effects of CAFs on OSCC cell proliferation, invasion, and migration. These findings suggested that CAFs are one of lipid sources required for OSCC progression. Mechanistically, AKT signaling activation was involved in the upregulation of p-ACLY level and lipid synthesis in CAFs. Interleukin-8 (IL8), an exocrine cytokine of OSCC cells, could activate AKT and then phosphorylate ACLY in fibroblasts. This study suggested that the IL8/AKT/p-ACLY axis could be considered as a potential target for OSCC treatment.

Melatonin inhibits the stemness of head and neck squamous cell carcinoma by modulating HA synthesis via the FOSL1/HAS3 axis.

Hyaluronic acid (HA) is a glycosaminoglycan and the main component of the extracellular matrix (ECM), which has been reported to interact with its receptor CD44 to play critical roles in the self-renewal and maintenance of cancer stem cells (CSCs) of multiple malignancies. Melatonin is a neuroendocrine hormone with pleiotropic antitumor properties. However, whether melatonin could regulate HA accumulation in the ECM to modulate the stemness of head and neck squamous cell carcinoma (HNSCC) remains unknown. In this study, we found that melatonin suppressed CSC-related markers, such as CD44, of HNSCC cells and decreased the tumor-initiating frequency of CSCs in vivo. In addition, melatonin modulated HA synthesis of HNSCC cells by downregulating the expression of hyaluronan synthase 3 (HAS3). Further study showed that the Fos-like 1 (FOSL1)/HAS3 axis mediated the inhibitory effects of melatonin on HA accumulation and stemness of HNSCC in a receptor-independent manner. Taken together, melatonin modulated HA synthesis through the FOSL1/HAS3 axis to inhibit the stemness of HNSCC cells, which elucidates the effect of melatonin on the ECM and provides a novel perspective on melatonin in HNSCC treatment.

Modified chitosan with different phenolic acids: Characterization, physicochemical properties, and biological activity.

This study synthesized five phenolic acid-chitosan copolymers utilizing the carbodiimide-mediated chemical crosslinking reaction. Comprehensive evaluations were conducted on their structural attributes, physicochemical properties, and biological activities. Fourier transform infrared confirmed successful grafting of phenolic acids onto chitosan via amide linkages. Additionally, ultraviolet-visible absorption spectroscopy and proton nuclear magnetic resonance analyses revealed novel absorption peaks between 200 and 400 nm and 6.0-8.0 ppm, respectively, attributable to the incorporated phenolic acids. Notably, the chitosan-gentisate acid copolymer exhibited significantly enhanced biological activity (p < 0.05) compared to pure chitosan and the other four conjugates, attributed to its highest grafting degree of approximately 295.93 mg/g. These modified chitosan derivatives effectively preserved the quality of sea bass (Lateolabrax japonicus) during refrigerated storage, extending its shelf-life by up to 9 days, 7 days, and 4 days relative to control, chitosan, and gentisate acid groups.

Effects of slightly acidic electrolyzed water combined with ԑ-polylysine-chitooligosaccharide Maillard reaction products treatment on the quality of vacuum packaged sea bass (Lateolabrax japonicas).

In this study, a new natural preservative, ε-polylysine (ε-PL) and chitooligosaccharides (COS) Maillard reaction products (LC-MRPs), was prepared by Maillard reaction. The preservation effect of LC-MRPs combined with slightly acidic electrolyzed water (SAEW) pretreatment (SM) on vacuum-packed sea bass during refrigerated storage was evaluated. The results showed that after 16 days, SM treatment could effectively inhibit the microbial growth and prevent water migration in sea bass. In addition, the highest water holding capacity (69.79 %) and the best sensory characteristics, the lowest malonaldehyde (MDA) (58.96 nmol/g), trimethylamine (TMA) (3.35 mg/100 g), total volatile basic nitrogen (TVB-N) (16.93 mg N/100 g), myofibril fragmentation index (MFI) (92.2 %) and TCA-soluble peptides (2.16 µmol tyrosine/g meat) were related to SM group. Combined with sensory analysis, we can conclude that the combined treatment of SAEW and LC-MRPs could prolong the shelf-life of sea bass for another 11 days compared with the DW group. Results disclosed that the composite treatment of SAEW and LC-MRPs is a promising technology to improve the shelf-life of vacuum-packed sea bass during refrigerated storage.

Efficacy of personalized 3D-printed osteotomy guide in maximizing fibular utilization and minimizing graft length for reconstruction of large mandibular defect.

OBJECTIVE: The study addresses the long-standing challenge of insufficient length in vascularized fibular flaps when reconstructing large mandibular defects that require dual-barrel grafts. Employing personalized 3D-printed osteotomy guides, the study aims to optimize fibular utilization and minimize the required graft length. MATERIAL AND METHODS: Two reconstruction methods for distal bone defects were compared: a fold-down (FD) group that employed a specialized osteotomy guide for folding down a triangular bone segment, and a traditional double-barrel (DB) group. Metrics for comparison included defect and graft lengths, as well as the graft-to-defect length ratio. Postoperative quality of life was assessed using the University of Washington Quality of Life questionnaire (UW-QoL). RESULT: Both FD and DB groups achieved successful mandibular reconstruction. Despite larger defects in the FD group (117 ± 31.35 mm vs 84 ± 35.34 mm, p = 0.028), the used fibula length was not statistically longer in the FD group. The median ratio of graft-to-defect length was also lower in the FD group (1.327 vs 1.629, p = 0.024), suggesting that FD required only 82.47% of the graft length needed in the DB approach. Quality of life scores post-surgery were comparable between the groups. CONCLUSION: Personalized 3D-printed osteotomy guides enhance fibula graft efficacy for reconstructing larger mandibular defects, necessitating shorter graft lengths while preserving postoperative quality of life. CLINICAL RELEVANCE: This study confirms the utility of 3D printing technology as an effective and precise tool in orthopedic surgery, particularly for complex reconstructions like large mandibular defects. It suggests a viable alternative that could potentially revolutionize current practices in bone grafting.

One/Two-Photon-Excited ESIPT-Attributed Coordination Polymers with Wide Temperature Range and Color-Tunable Long Persistent Luminescence.

The multiple metastable excited states provided by excited-state intramolecular proton transfer (ESIPT) molecules are beneficial to bring temperature-dependent and color-tunable long persistent luminescence (LPL). Meanwhile, ESIPT molecules are intrinsically suitable to be modulated as D-π-A structure to obtain both one/two-photon excitation and LPL emission simultaneously. Herein, we report the rational design of a dynamic CdII coordination polymer (LIFM-106) from ESIPT ligand to achieve the above goals. By comparing LIFM-106 with the counterparts, we established a temperature-regulated competitive relationship between singlet excimer and triplet LPL emission. The optimization of ligand aggregation mode effectively boost the competitiveness of the latter. In result, LIFM-106 shows outstanding one/two-photon excited LPL performance with wide temperature range (100-380 K) and tunable color (green to red). The multichannel radiation process was further elucidated by transient absorption and theoretical calculations, benefiting for the application in anti-counterfeiting systems.

Trinuclear Re(I)-Coordinated Organic Cage as the Supramolecular Photocatalyst for Visible-Light-Driven CO2 Reduction.

Photocatalytic reduction of excess CO2 in the atmosphere to value-added chemicals by visible light can be an effective solution to fuel shortage and global warming. Considering these issues, we designed and successfully synthesized a trinuclear Re(I)-coordinated organic cage (Re-C4R) as the supramolecular photocatalyst. Photophysical, electrochemical properties, and photocatalytic performance comparison of Re-C4R and its mononuclear analogue Re-bpy are discussed in detail. Notably, the covalent linkage of three Re(I) subunits in Re-C4R leads to TONCO = 691 (per Re(I) site in 4 h) more than three times as much as TONCO = 208 of Re-bpy. Compared to Re-bpy, higher current enhancement in the control CV experiments under CO2 was observed for Re-C4R. CO2 adsorption process can be promoted because of the cryptand structure and multiple amine groups of Re-C4R. Moreover, decay lifetimes of Re-C4R are shorter than those of Re-bpy in the ultrafast transient absorption (TA) and photoluminescence (PL) decay spectra, indicating that the trinuclear cryptate structure of Re-C4R could facilitate electron transfer efficiency during CO2 reduction.

Dentinogenic ghost cell tumor revisited from a single institution in China with focus on adenoid ameloblastoma-like features.

OBJECTIVE: The present study aims to identify adenoid ameloblastoma (AdAM) from previously diagnosed cases of dentinogenic ghost cell tumor (DGCT), and gain insight to the possible relationship between AdAM and DGCT. METHODS: DGCT cases diagnosed between 2006 and 2022 were re-examined with focus on the AdAM-like features. RESULTS: A total of nine patients were included. Seven patients were males and two were females. The mean age was 38.0 ± 16.0 years. Five tumors occurred in the maxilla and four in the mandible, with a remarkable predilection for the posterior regions of both jaws. Microscopically, dentinoid material deposition was present in all cases. The ghost cells were absent in two cases. Rare ghost cells (<1%) were observed in three cases, and a higher proportion of ghost cells (5%-20%) were present in the remaining four cases. All cases showed prominent AdAM-like features, including duct-like structures, whorls/morules, and cribriform architecture. According to the diagnostic criteria proposed by the 2022 WHO classification, five cases without or with rare ghost cells were reclassified as AdAM. The other four cases including a higher proportion of ghost cells consisted of a mixture of DGCT and AdAM histopathologic patterns. CONCLUSION: Our results confirmed that the AdAM-like features had been largely overlooked in the diagnosis of DGCT at our institution in the past. Whilst a subset can now be more accurately classified as AdAM, some tumors showed overlapping morphological features between AdAM and DGCT, suggesting that the two may represent a spectrum of the same entity.

Metal-Phenolic Network-Facilitated "Foe-to-Friend" Conversion of Melittin for Cancer Immunotherapy with Boosted Abscopal Effect.

As a naturally occurring cytolytic peptide, melittin (Mel) has strong cytolytic activity and is a potent therapeutic peptide for cancer therapy. However, the serious hemolytic activity of Mel largely impedes its clinical applications. In this work, based on the strong interactions between proteins/peptides and polyphenols, we develop a tannic acid-Fe3+ metal-phenolic network (MPN)-based strategy that can convert Mel from foe to friend via shielding its positive charges and reducing its hemolytic activity. Besides, an immune adjuvant resiquimod (R848) is also introduced for immunostimulation, affording the final Mel- and R848-coloaded nanodrug. The Mel-caused membrane disruption can induce immunogenic cell death for immunostimulation, R848 can act as an immune adjuvant to further facilitate the immunostimulatory effect, and the tannic acid-Fe3+ MPN-mediated Fenton reaction can produce reactive oxygen species for cancer treatment. Further experiments reveal that the nanodrug can effectively cause immunogenic cell death of tumor cells and arouse robust intratumoral and systemic antitumor immunostimulation. In the bilateral tumor-bearing mouse models, the nanodrug considerably destroys the primary tumor and also boosts the abscopal effect to ablate the distant tumor. Collectively, the MPN-facilitated "foe-to-friend" strategy may promote the practical applications of Mel and foster the development of cancer immunotherapeutics.