Functional hydrogels for treatment of dental caries

Dental pulp stem cells-loaded kartogenin-modified hydrogel microspheres with chondrocyte differentiation property for cartilage repair

Developing functional hydrogels for treatment of oral diseases

AbstractOral disease is a severe healthcare challenge that diminishes people's quality of life. Functional hydrogels with suitable biodegradability, biocompatibility, and tunable mechanical properties have attracted remarkable interest and have been developed for treating oral diseases. In this review, we present up‐to‐date research on hydrogels for the management of dental caries, endodontics, periapical periodontitis, and periodontitis, depending on the progression of dental diseases. The strategies of hydrogels for treating oral mucosal diseases and salivary gland diseases are then classified. After that, we focus on the application of hydrogels related to tumor therapy and tissue defects. Finally, the review prospects the restrictions and the perspectives on the utilization of hydrogels in oral disease treatment. We believe this review will promote the advancement of more amicable, functional and personalized approaches for oral diseases.

Bee Sting-Inspired Inflammation-Responsive Microneedles for Periodontal Disease Treatment

Periodontal lesions are common and frustrating diseases that impact life quality. Efforts in this aspect aim at developing local drug delivery systems with better efficacy and less toxicity. Herein, inspired by the sting separation behavior of bees, we conduct novel reactive oxygen species (ROS)-responsive detachable microneedles (MNs) that carry antibiotic metronidazole (Met) for controllable periodontal drug delivery and periodontitis treatment. Benefiting from the needle-base separation ability, such MNs can penetrate through the healthy gingival to reach the gingival sulcus's bottom while offering minimal impact to oral function. Besides, as the drug-encapsulated cores were protected by poly (lactic-co-glycolic acid) (PLGA) shells in MNs, the surrounding normal gingival tissue is not affected by Met, resulting in excellent local biosafety. Additionally, with the ROS-responsive PLGA-thioketal-polyethylene glycol MN tips, they can be unlocked to release Met directly around the pathogen under the high ROS in the periodontitis sulcus, bringing about improved therapeutic effects. Based on these characteristics, the proposed bioinspired MNs show good therapeutic results in treating a rat model with periodontitis, implying their potential in periodontal disease.

Photosensitizer-immunotherapy integrated microneedles for preventing tumor recurrence and metastasis

Regulating tumor cholesterol microenvironment to enhance photoimmunotherapy in oral squamous cell carcinoma

Cholesterol Metabolism Modulation Nanoplatform Improves Photo‐Immunotherapeutic Effect in Oral Squamous Cell Carcinoma

Thrombus-targeted nano-agents for NIR-II diagnostic fluorescence imaging-guided flap thromboembolism multi-model therapy

AbstractIn oral and maxillofacial surgery, flap repair is essential to the quality of postoperative life. Still, thrombosis is fatal for the survival of the flaps. Besides, some postoperative thrombotic diseases, such as pulmonary embolism, also intimidate patients’ life. The traditional diagnostic methods are still limited by a large amount of hardware and suffer from inconvenience, delay, and subjectivity. Moreover, the treatments mainly rely upon thrombolytics, such as urokinase (UK) plasminogen activator, which may cause bleeding risk, especially intracerebral hemorrhage. Herein, a kind of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing a first near-infrared window (NIR-I) phototheranostic agent Y8 and urokinase plasminogen activator (UK) as the core, and modified with the fibrin-targeting peptide Gly–Pro–Arg–Pro–Pro (GPRPP) were developed for the flap and postoperative thromboembolism treatment (named GPRPP-Y8U@P). The conjugated molecule Y8 endows GPRPP-Y8U@P with the capacity of NIR-II imaging and excellent photothermal/photodynamic therapeutic effects. In vivo experiments demonstrated that GPRPP-Y8U@P could quickly locate thrombus by NIR-II fluorescence imaging, and semi-quantitative analysis of the embolized blood vessels' paraffin section verified its thrombolytic efficiency. Additionally, the urokinase trapped in the NPs would not result in nonspecific bleeding, tremendously improving physical security and curative effects with minimizing side effects. Overall, the advantages of GPRPP-Y8U@P, such as precise localization of the thrombus, thrombus ablation in the site, and mild side effects, demonstrated the attractiveness of this approach for effective clinical monitoring of thrombus therapy.

Rhythm Mild‐Temperature Photothermal Therapy Enhancing Immunogenic Cell Death Response in Oral Squamous Cell Carcinoma

Multifunctional photodynamic/photothermal nano-agents for the treatment of oral leukoplakia

AbstractOral leukoplakia (OLK) has gained extensive attention because of the potential risk for malignant transformation. Photosensitizers (PSs) played an indispensable role in the photodynamic therapy (PDT) of OLK, but the poor light sensitivity greatly hampered its clinical application. Herein, a novel organic photosensitive ITIC-Th nanoparticles (ITIC-Th NPs) were developed for OLK photodynamic/photothermal therapy (PTT). ITIC-Th NPs present both high photothermal conversion efficiency (~ 38%) and suitable reactive oxygen species (ROS) generation ability under 660 nm laser irradiation, making them possess excellent PDT and PTT capability. In 4-nitroquinoline 1-oxide (4NQO)-induced oral precancerous animal models, ITIC-Th NPs effectively suppress the OLK's cancerization without apparent topical or systemic toxicity in vivo. This study offers a promising therapeutic strategy for PDT and PTT in OLK treatment, and this study is the first interdisciplinary research in the field of multimodal therapy for OLK. Graphical Abstract

HSP90AB1 Promotes the Proliferation, Migration, and Glycolysis of Head and Neck Squamous Cell Carcinoma

Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. Heat shock protein 90 alpha family class B member 1 (HSP90AB1) is highly expressed in a variety of cancers and is associated with poor prognosis, however, its role in HNSCC is still poorly understood. This study aimed to explore the function HSP90AB1 played in HNSCC progression. Methods: The expression level of HSP90AB1 in HNSCC was analyzed by bioinformatics analysis and western blotting, and its relationship with clinicopathological parameters was analyzed by bioinformatics analysis and immunohistochemistry. Three stable HSP90AB1 knockdown HNSCC cell lines were constructed by lentiviral transfection. The effect of HSP90AB1 knockdown on the proliferation and migration of HNSCC cells was tested by CCK-8 assay, EdU incorporation assay, colony formation assay, nude mouse xenograft models, transwell migration assay, wound healing assay, and western blotting. The effect of HSP90AB1 knockdown on glycolysis in HNSCC cells was assessed by quantitative real-time PCR and related assay kits. Finally, the levels of Akt and phospho-Akt (Ser473) proteins after HSP90AB1 knockdown were detected by western blotting. Results: HSP90AB1 was highly expressed in HNSCC and associated with T grade, lymph node metastasis, and prognosis. Knockdown of HSP90AB1 inhibited the proliferation, migration, and glycolysis of HNSCC, and reduced the level of phospho-Akt. Conclusion: HSP90AB1 functions as an oncogene in HNSCC, and has the potential to become a prognostic factor and therapeutic target.

Fused-Ring Small-Molecule-Based Bathochromic Nano-agents for Tumor NIR-II Fluorescence Imaging-Guided Photothermal/Photodynamic Therapy

A Novel NIR-II Theranostic Agent: A Win–win Strategy of Tracing and Blocking Tumor-associated Vessels for Oral Squamous Cell Carcinoma

Abstract Tumor vessel co-option is a crucial predictor for tumor invasiveness but is easy to ignore in tumor vascular targeting therapy. A high density of tumor vessel co-option located alongside the tumor frontier predicted a high tendency of tumor invasion and regional metastasis. Herein, a novel NIR-II nanoagent (CS NPs) was constructed with an organic COi8DFIC dye and sorafenib, which demonstrated high tissue penetration and low tissue autofluorescence, enabling imaging of vessel co-option and tumor micrometastasis. This nanotherapeutic agent displayed considerably improved quantum yield of fluorescence (0.89%), high ROS generation and fairly good biosafety in vivo. Compared with indocyanine green (ICG), CS NPs exhibited better photostability and photothermal conversion efficiency. By tracking tumor-associated vessels and real-time tumor imaging, CS NPs could open/stop vascular targeting therapy by laser on/off. The combination of vessel disruption and imaging-guided photothermal therapy/photodynamic therapy provided a win–win strategy for oral squamous cell carcinoma (OSCC).

Peroxidase-mimicking evodiamine/indocyanine green nanoliposomes for multimodal imaging-guided theranostics for oral squamous cell carcinoma

Novel NIR-II semiconducting molecule incorporating sorafenib for imaging guided synergetic cancer phototherapy and anti-angiogenic therapy

With the addition of sorafenib into organic semiconducting molecule T8IC, TS nanoparticles (NPs) were formed by nanoprecipitation with synergetic anti-angiogenic and phototheranostic effects.

Novel semiconducting nano-agents incorporating tirapazamine for imaging guided synergistic cancer hypoxia activated photo-chemotherapy

The imaging guided synergistic photothermal, photodynamic and chemical therapy of ITTC NPs and TPZ have great potential for clinical transformation in tumor diagnosis and therapy.

Organic Near-Infrared-II Nanophotosensitizer for Safe Cancer Phototheranostics and Improving Immune Microenvironment against Metastatic Tumor

Anti-LDLR modified TPZ@Ce6-PEG complexes for tumor hypoxia-targeting chemo-/radio-/photodynamic/photothermal therapy

A tumor hypoxia-targeting theranostic nanoplatform based on Ce6-PEG and tirapazamine for imaging diagnosis and multimodal therapy.

Polycyclic naphthalenediimide-based nanoparticles for NIR-II fluorescence imaging guided phototherapy

Hypoxia-Targeting Multifunctional Nanoparticles for Sensitized Chemotherapy and Phototherapy in Head and Neck Squamous Cell Carcinoma

Optical nano-agents in the second near-infrared window for biomedical applications

This review summarizes the recent advances of optical nano-agents for various biomedical applications in the NIR-II window.

Metformin enhances gefitinib efficacy by interfering with interactions between tumor-associated macrophages and head and neck squamous cell carcinoma cells

HOTTIP Functions as a Key Candidate Biomarker in Head and Neck Squamous Cell Carcinoma by Integrated Bioinformatic Analysis

Background. Accumulating evidence has demonstrated the pivotal role of long noncoding RNAs (lncRNAs) in competing endogenous RNA (ceRNA) networks for predicting survival and evaluating prognosis in cancer patients. However, the pathogenesis of head and neck squamous cell carcinoma (HNSCC) remains unclear, and prognostic biomarkers for HNSCC are still lacking. Methods. A total of 546 RNA sequencing profiles of HNSCC patients with clinical outcome data were obtained from the Cancer Genome Atlas (TCGA) database, providing a large sample of RNA sequencing data. From these, 71 Long noncoding RNAs lncRNAs, 8 microRNAs (miRNAs), and 16 messenger RNAs (mRNAs) were identified to construct a HNSCC-specific ceRNA network (fold change >2, P < 0.05). Univariate and multivariate Cox proportional regression models were used to assess independent indicators of prognosis. Then the expression of lncRNAs harboring prognostic value was validated in human HNSCC cell lines and tumor samples from our cohort and another two datasets from GEO (Gene Expression Omnibus) databases. Results. As a result, a 3-mRNA signature and 6-lncRNA signature were identified. The six-lncRNA signature exhibited the highest prognostic value. Notably, in the six lncRNAs, HOTTIP showed the greatest prognostic value and was significantly correlated with clinical stage and histological grade of HNSCC patients. Furthermore, it was proved that HOTTIP was upregulated in HNSCC cell lines and cancerous tissues compared with corresponding normal cell lines and normal tissues. Functional assessment analysis revealed that HOTTIP might play a key role in the oncogenesis and progression of HNSCC. Conclusion. The present study deepened our understanding of the ceRNA-related regulatory mechanism in the pathogenesis of HNSCC and identified candidate prognostic biomarkers for clinical outcome prediction in HNSCC. HOTTIP may function as a key candidate biomarker in HNSCC and serve as a prognostic marker for HNSCC patients.

Rh type C-glycoprotein functions as a novel tumor suppressor gene by inhibiting tumorigenicity and metastasis in head and neck squamous cell carcinoma

Carrier-free nano-integrated strategy for synergetic cancer anti-angiogenic therapy and phototherapy

Herein, a nano-integrated strategy was used to combine an anti-angiogenic agent sorafenib and a photosensitizer chlorin e6 to form carrier-free multifunctional nanoparticles (SC NPs) for synergetic anti-angiogenic therapy and phototherapy.

Novel acceptor–donor–acceptor structured small molecule-based nanoparticles for highly efficient photothermal therapy

Acceptor–donor–acceptor structured ITIC small molecule based nanoparticles are explored for highly efficient photothermal therapy application.

Antitumor effect of a Pt-loaded nanocomposite based on graphene quantum dots combats hypoxia-induced chemoresistance of oral squamous cell carcinoma

Metformin sensitizes hypoxia-induced gefitinib treatment resistance of HNSCC via cell cycle regulation and EMT reversal